http://2012.igem.org/wiki/index.php?title=Special:Contributions&feed=atom&limit=50&target=Stephanielubbers2012.igem.org - User contributions [en]2024-03-29T11:09:44ZFrom 2012.igem.orgMediaWiki 1.16.0http://2012.igem.org/Team:TU-Delft/HP/DocTalkTeam:TU-Delft/HP/DocTalk2012-11-14T14:23:36Z<p>Stephanielubbers: </p>
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<h2> Medical applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<br/><h3>Talk with Dr. Lutter about the applicability of our research within the medical field </h3><br />
To get a better overview of what the medical field would think of our research, we talked to Dr. Rene Lutter (is doing research at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands into the functioning of granuloma in tuberculosis amongst others by analyzing breath-condensate).<br />
</br><br />
<br/>After we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably lead up to a new detection method in the medical field in the future. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/><b>Intensive care </b><br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br><b>Resistant TB </b><br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/><b>HIV and TB</b> <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/><b>Fact:</b><i> From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB.</i><br />
<a href="http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx" target="_blank">Source: Medecins sans Frontieres </a><br/><br />
<br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by being able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. And we would like to thank Dr. Rene Lutter for his input in our project! <br/> </div><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T02:06:03Z<p>Stephanielubbers: </p>
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<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td width="80%"><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"><img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg" width="150"/><br><h6>Source: wikimedia commons</h6></a><br />
</td><br />
</table><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T02:05:14Z<p>Stephanielubbers: </p>
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<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td width="80%"><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"><img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg" width="150"/><br><h6>source: wikimedia commons</h6></a><br />
</td><br />
</table><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690" /><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T02:04:57Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td width="80%"><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"><img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg" width="150"/><br><h6>source:wikimedia commons</h6></a><br />
</td><br />
</table><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690" /><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T02:04:17Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td width="80%"><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"><img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg" width="150"/><br><h6>source : wikimedia commons</h6></a><br />
</td><br />
</table><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690" /><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T02:03:10Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td width="60%"><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td ALIGN="right"><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"><img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg" width="150"/><br><h6>source : wikimedia commons</h6></a><br />
</td><br />
</table><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690" /><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T02:01:47Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td width="60%"><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td align="right"><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"><img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg" width="150"/><br><h6>source : wikimedia commons</h6></a><br />
</td><br />
</table><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T02:01:09Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td width="60%"><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"><img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg" width="150"/><br><h6>source : wikimedia commons</h6></a><br />
</td><br />
</table><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690" /><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T01:59:30Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td width="60%"><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"><img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg" width="200"/><br><h6>source : wikimedia commons</h6></a><br />
</td><br />
</table><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T01:58:36Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
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<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"><img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg" width="200"/><br><h6>source:wikimedia commons</h6></a><br />
</td><br />
</table><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690" /><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T01:57:46Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"><img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"/></a><br />
</td><br />
</table><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T01:57:09Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
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<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
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<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg" img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"></a><br />
</td><br />
</table><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690" /><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T01:56:40Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><table><br />
<td><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</td><br />
<td><br />
<a href="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg" img src="http://upload.wikimedia.org/wikipedia/commons/a/a5/%22Guard_Against_Tuberculosis%22_-_NARA_-_514425.jpg"></a><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T01:53:24Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
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<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
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<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms act outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690" /><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T01:51:25Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="150"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T01:50:42Z<p>Stephanielubbers: </p>
<hr />
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<head><title>Human Practice</title><br />
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<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png" width="50"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690" /><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T01:50:02Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> <table><td>The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
</td><td><img src="https://static.igem.org/mediawiki/2012/b/b2/Snifferometer_device.png"></td></table><br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
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<head><title>Human Practice</title><br />
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<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle when translated into a product, could make a difference. To answer this we evaluate the most important parts of these questions below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB cells usually attack the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. People with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV: 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable, fast and also suitable for the frontline at the same time. Not suitable for the frontline because it needs extensive facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and should give quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the <a href="https://2012.igem.org/Team:TU-Delft/Modeling/StructuralModeling">structural model page</a>.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the <a href="https://2012.igem.org/File:Component_sheet.PNG">compound sheet</a> on the <a href="https://2012.igem.org/Team:TU-Delft/Snifferometer">Sniffer-o-meter</a> page. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods cost per test, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~4 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately four hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms ourselves, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 4 hours.<br><br />
• Cheap: compared to all the other diagnosing methods, the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable device. This means that this way of diagnosing can take place in environments up to +- 30 Celsius when cooled supply is possible.<br><br />
• Operational: with the clear operational instructions the device would be easy to operate. And it would not be necessary to have professionally trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the device.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in July 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in July 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/DocTalkTeam:TU-Delft/HP/DocTalk2012-10-27T01:16:30Z<p>Stephanielubbers: </p>
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<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
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<h2> Medical applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<br/><h3>Talk with Dr. Lutter about the applicability of our research within the medical field </h3><br />
To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter who is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. </br><br />
<br/>As we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably lead up to a new detection method in the medical field in the future. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/><b>Intensive care </b><br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br><b>Resistant TB </b><br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/><b>HIV and TB</b> <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/><b>Fact:</b><i> From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB.</i><br />
<a href="http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx" target="_blank">Source: Medecins sans Frontieres </a><br/><br />
<br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. And we would like to thank Dr. Rene Lutter for his input in our project! <br/> </div><br />
<br />
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<h2> Medical applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<br/><h3>Talk with Dr. Lutter about the applicability of our research within the medical field </h3><br />
To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter who is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. </br><br />
<br/>As we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably eventually lead up to a new detection method in the medical field. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/><b>Intensive care </b><br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br><b>Resistant TB </b><br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/><b>HIV and TB</b> <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/><b>Fact:</b><i> From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB.</i><br />
<a href="http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx" target="_blank">Source: Medecins sans Frontieres </a><br/><br />
<br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. And we would like to thank Dr. Rene Lutter for his input in our project! <br/> </div><br />
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<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and gives quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the structural model page.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the compound sheet on the Sniffer-o-meter page on our wiki. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~3.5 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately 4 hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms our self, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 3.5 hours.<br><br />
• Cheap: compared to all the other diagnosing methods (see table), the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable devise. This means that this way of diagnosing can take place everywhere.<br><br />
• Operational: with the right operational instructions the device would be easy to operate. And it would not be necessary have to be professional trained medical people. </br><br />
• Safety: it is a safe device to use since the modified organisms do not have a chance to survive outside the devise.<br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
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<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and gives quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM [1] concentrations, the rat receptor 400 nM [2] concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the structural model page.<br />
<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al. of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients [3]. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples [4]. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time [5]. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol [6].Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
<br />
</br><h6>Measurement techniques</h6> The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique [7]. Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the compound sheet on the Sniffer-o-meter page on our wiki. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~3.5 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately 4 hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms our self, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 3.5 hours.<br><br />
• Cheap: compared to all the other diagnosing methods (see table), the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable devise. This means that this way of diagnosing can take place everywhere.<br><br />
• Operational: with the right operational instructions the device would be easy to operate. And it would not be necessary have to be professional trained medical people. </br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T00:30:25Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
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<head><title>Human Practice</title><br />
<body><br />
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<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and gives quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM concentrations, the rat receptor 400 nM concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the structural model page.<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al.4 of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol. Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
</br><h6>Measurement techniques</h6> The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique . Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the compound sheet on the Sniffer-o-meter page on our wiki. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~3.5 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately 4 hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms our self, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 3.5 hours.<br><br />
• Cheap: compared to all the other diagnosing methods (see table), the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable devise. This means that this way of diagnosing can take place everywhere.<br><br />
• Operational: with the right operational instructions the device would be easy to operate. And it would not be necessary have to be professional trained medical people. </br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<a name="P9"><h2>References</h2> </a><br />
<h6><br />
[1] Ilona Mandrica et al. Evidence for constitutive dimerization of niacin receptor subtypes (2010) Biochem. and Biophys. Research Comm. Vol. 395 pp. 281–287<br/><br />
[2] Alan Wise et al. Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid (2003) The Journal of Biol. Chem. Vol. 278, No.11, pp 9869-9874 <br/><br />
[3] Georgies F. Mgode et al. Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract (2012) J. Clin. Microbiol. 50(2):27<br/><br />
[4] Mona Syhre et al. The scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[5] Mona Syhre and Stephen T. Chambers The scent of Mycobacterium tuberculosis (2008) Tuberculosis 88, 317–323<br/><br />
[6] Monay Syhre the scent of Mycobacterium tuberculosis – Part II breath (2009) Tuberculosis 89 263–266<br/><br />
[7] Irina Vetter Development and Optimization of FLIPR High Throughput Calcium Assays for Ion Channels and GPCRs (2012) Advances in Experimental Medicine and Biology Volume 740, 45-82<br/><br />
<br/><br />
<br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690" /><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T00:26:33Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br/><br />
<br/><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and gives quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM concentrations, the rat receptor 400 nM concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the structural model page.<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al.4 of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol. Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
</br><h6>Measurement techniques</h6> The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique . Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the compound sheet on the Sniffer-o-meter page on our wiki. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~3.5 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately 4 hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms our self, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 3.5 hours.<br><br />
• Cheap: compared to all the other diagnosing methods (see table), the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable devise. This means that this way of diagnosing can take place everywhere.<br><br />
• Operational: with the right operational instructions the device would be easy to operate. And it would not be necessary have to be professional trained medical people. </br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690" /><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T00:25:46Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<h2>Implementation Study</h2><br><br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and gives quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM concentrations, the rat receptor 400 nM concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the structural model page.<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al.4 of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol. Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
</br><h6>Measurement techniques</h6> The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique . Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the compound sheet on the Sniffer-o-meter page on our wiki. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~3.5 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately 4 hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms our self, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 3.5 hours.<br><br />
• Cheap: compared to all the other diagnosing methods (see table), the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable devise. This means that this way of diagnosing can take place everywhere.<br><br />
• Operational: with the right operational instructions the device would be easy to operate. And it would not be necessary have to be professional trained medical people. </br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T00:24:04Z<p>Stephanielubbers: </p>
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<br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and gives quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM concentrations, the rat receptor 400 nM concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the structural model page.<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al.4 of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol. Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
</br><h6>Measurement techniques</h6> The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique . Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the compound sheet on the Sniffer-o-meter page on our wiki. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~3.5 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately 4 hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms our self, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br><br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 3.5 hours.<br><br />
• Cheap: compared to all the other diagnosing methods (see table), the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable devise. This means that this way of diagnosing can take place everywhere.<br><br />
• Operational: with the right operational instructions the device would be easy to operate. And it would not be necessary have to be professional trained medical people. </br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T00:23:30Z<p>Stephanielubbers: </p>
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<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
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<div id="contentbox" style="text-align:justify;"><br />
<br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and gives quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM concentrations, the rat receptor 400 nM concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the structural model page.<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al.4 of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol. Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
</br><h6>Measurement techniques</h6> The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique . Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the compound sheet on the Sniffer-o-meter page on our wiki. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~3.5 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately 4 hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms our self, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br><br />
• Fast: to obtain the final results of the test it will take approximately 3.5 hours.<br><br />
• Cheap: compared to all the other diagnosing methods (see table), the Sniffer-o-meter would be the cheapest to use.<br><br />
• Accessible: the Sniffer-o-meter is a small and portable devise. This means that this way of diagnosing can take place everywhere.<br><br />
• Operational: with the right operational instructions the device would be easy to operate. And it would not be necessary have to be professional trained medical people. </br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T00:22:06Z<p>Stephanielubbers: </p>
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<br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and gives quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM concentrations, the rat receptor 400 nM concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the structural model page.<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al.4 of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol. Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
</br><h6>Measurement techniques</h6> The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique . Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the compound sheet on the Sniffer-o-meter page on our wiki. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~3.5 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately 4 hours.<br />
<br />
</br><h6>Safety</h6> <br />
While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms our self, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival.<br />
<br />
</p><br />
<h3>Conclusion</h3><br />
<br> <br />
<p>The advantages of the Sniffer-o-meter:</br><br />
<br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br />
• Fast: to obtain the final results of the test it will take approximately 3.5 hours.<br />
• Cheap: compared to all the other diagnosing methods (see table), the Sniffer-o-meter would be the cheapest to use.<br />
• Accessible: the Sniffer-o-meter is a small and portable devise. This means that this way of diagnosing can take place everywhere.<br />
• Operational: with the right operational instructions the device would be easy to operate. And it would not be necessary have to be professional trained medical people. </br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T00:19:02Z<p>Stephanielubbers: </p>
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<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
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<div id="contentbox" style="text-align:justify;"><br />
<br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<img src="https://static.igem.org/mediawiki/igem.org/c/cb/Tb_pictures.jpg"width="570"/><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and gives quickly a reliable result. </p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM concentrations, the rat receptor 400 nM concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the structural model page.<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al.4 of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol. Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
</br><h6>Measurement techniques</h6> The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique . Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
<br />
</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
<br />
</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the compound sheet on the Sniffer-o-meter page on our wiki. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods, one can concluded that our method will be the cheapest. <br />
<br />
</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
<br />
</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~3.5 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately 4 hours.<br />
<br />
</br><h6>Safety</h6> <br />
<br>While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms our self, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival. </br><br />
<br />
</p><br />
<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter:<br />
<br> <br />
• Non-invasive: the device only needs a sample of saliva of the patient. </br><br />
<br><br />
• Fast: to obtain the final results of the test it will take approximately 3.5 hours. </br><br />
<br><br />
• Cheap: compared to all the other diagnosing methods (see table), the Sniffer-o-meter would be the cheapest to use. </br><br />
<br><br />
• Accessible: the Sniffer-o-meter is a small and portable devise. This means that this way of diagnosing can take place everywhere. </br><br />
<br><br />
• Operational: with the right operational instructions the device would be easy to operate. And it would not be necessary have to be professional trained medical people. </br><br />
<br><br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HP/StudyTeam:TU-Delft/HP/Study2012-10-27T00:14:54Z<p>Stephanielubbers: </p>
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<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
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<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
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<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
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<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
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<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
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<h3>Our ideal Solution</h3><br />
<p>The intended use of the device is in a diagnosis area in a controlled environment like a medical facility or even town hall. Further the device should be easy to operate, have low costs, and gives quickly a reliable result. </p><br />
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<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Therefore remote areas can be easily reached. In cool areas (4 °C) dry yeast can be contained for two years. The environment to grow yeast in dry warm countries is far from optimal, but encapsulating the yeast growth in a small container can facilitate growth. A container with temperature indicator can serve as guideline to see where it has to be placed during the measurement. It should also have a filter which exchanges gasses coming from the yeast and the TB bacteria and the environment, holding the organisms in the container. Ideally the area between the growing media and the air is large, without drying out. <br />
</br><h6>Affinity of receptor Gpr109A towards methyl nicotinate</h6>Human Gpr109A expressed in HEK293 cells have affinities towards nicotinic acid going down to 204 +- 67 nM concentrations, the rat receptor 400 nM concentrations (EC50 values). For yeast an EC50 concentration of 904 +- 28 nM2 is measured when human Gpr109A receptors are expressed together with the Gα chimeric subunit. Although a lot of derivatives are tested, information about affinities with methyl nicotinate are not found in literature. Structural simulations indicate that the binding energy (10 ns simulation) in the binding niche decreases approximately 50% in comparison with Niacin, the original ligand in the original receptor. This would result in lower affinity and this is why mutagenic studies on these receptors have been performed. The results of this can be found in the structural model page.<br />
</br><h6>Concentrations methyl nicotinate found in TB patients respiratory tract</h6>There are two general ways to find infection of TB cells in the respiratory tract. Either by analysis of the sputum or the breath of a tuberculosis patient. <br />
The analysis of breath can facilitate the diagnosis, as shown by the Syhre et al.4 of the university of Otago. The concentrations coming of tuberculosis patients is however very low, towards the femtomolar range. When the methyl nicotinate concentration in the breath is compared with the affinity of the reported receptors these concentrations are expected to be too low.<br />
The method used to let the species Rattus norvegicus identify TB cells is through analysis of plated sputum of TB patients. This way the speed of analysis and cost is improved in comparison with the general analysis through microscopy of acid-alcohol fast stained sputum samples. Plating of the sputum gives an exponential increase in tuberculosis cells present in this sputum, thus generating an exponential increase of methyl nicotinate over time. Thereby adding yeast media and dry yeast, yeast will glow up when the tuberculosis molecule is present. The sputum concentration of tuberculosis is 3 nmol. Whether this, in combination with the near presence of the TB source activates the receptor affinity is achievable is yet to be tested. <br />
</br><h6>Measurement techniques</h6> The Snifferomyces cells ideally generate light with minimal methyl nicotinate concentrations. The measurement can be measured when excited with a monochromatic light. A LED can serve as source for minimal spectral source, shown in the design of the Sniffer-o-meter. A light sensitive resistor can translate the smallest voltage difference into a numerical indication by an ADC chip. Signal amplification in the yeast and device and noise reduction in the device are to be characterized.<br />
Receptor activity is generally measured using the FLIPR technique . Using a similar light sensitive Ca2+ indicator system the yeast cells can be monitored on opening a co-expressed ion channel, activated by a receptor. A drawback here would be the interfering calcium transport of both TB and yeast cells.<br />
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</br><h6>Evaluating of test result</h6> We tested the Sniffer-o-meter and it is concluded that the device is capable of detecting the glowing GFP. So by reading of the Voltage from the voltmeter and compare the results to a reference, one can concluded weather a patient is infected or not. For a more detailed version, please go to the Sniffer-o-meter page on our wiki.<br />
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</br><h6>Costs</h6>Compared to the other diagnosing method for TB, the yeast cells used in the Sniffer-o-meter are the most cheaply replaceable parts. Furthermore the expenses of the device itself would sum up to a total of approximately 47 euro with integrated Voltmeter readout, see the compound sheet on the Sniffer-o-meter page on our wiki. By comparing the cost of the prototype of the Sniffer-o-meter and considering the low yeast costs with the other diagnosing methods, one can concluded that our method will be the cheapest. <br />
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</br><h6>Reliability</h6>Before the device would be on the market for actual use, more research, testing and evaluation are needed to give responsible scientific and ethical answer on the reliability.<br />
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</br><h6>Waiting time</h6>Hopefully the state of the GPCR cascade can be optimized before it is dried, leaving the enzymatic state intact. Yeast cells can serve as a fast (~3.5 hours) one time use device since it is a generally cheap method. In case of an inducible method, the protein concentrations can be altered one hour before the measurement. Before this the yeast has to be inoculated. Therefore waiting time for the result will be approximately 4 hours.<br />
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</br><h6>Safety</h6>While making the device, the team also thought of several safety questions. One of the main questions would be: How will the organisms acts outside of the device? Since we designed the organisms our self, we know that the yeast cells would not be able to survive on a different medium, in this case would be outside of the Sniffer-o-meter. The organisms are kept in a special container, and on the device itself is a warning placed for the operator, which states that this device should not be demolished. With all this in mind we could also say that the environment would not be negatively affected by the exposure of the modified organisms. One can concluded that it would not influence the ecology of the Earth, since we know that the yeast is not beneficial designed for survival. <br />
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<h3>Conclusion</h3> <br />
<p>The advantages of the Sniffer-o-meter <br />
• Non-invasive: the device only needs a sample of saliva of the patient. <br />
• Fast: to obtain the final results of the test it will take approximately 3.5 hours.<br />
• Cheap: compared to all the other diagnosing methods (see table), the Sniffer-o-meter would be the cheapest to use.<br />
• Accessible: the Sniffer-o-meter is a small and portable devise. This means that this way of diagnosing can take place everywhere.<br />
• Operational: with the right operational instructions the device would be easy to operate. And it would not be necessary have to be professional trained medical people. <br />
We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.<br />
.</p><br />
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<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/EthicsTeam:TU-Delft/Ethics2012-10-26T17:34:49Z<p>Stephanielubbers: </p>
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<td colspan="2" align="left"><h1><br/>Snifferomyces Ethics</h1></td><br />
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Through our iGEM project we are called to create a Biobrick of a yeast detecting odors. This not only is part of Synthetic Biology and is therefore prone to ethical considerations, but also due to it's chimeric properties can be called an invention and therefore can be a potential patent target. The question generated is where the line should be placed between finding and investigation and thus the question is raised: Is a chimeric protein an invention?<br />
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To begin with and trying to define synthetic biology we come up with the deliberate design of biological systems and living organisms using engineering principles. Synthetic biology<br />
is the creation of ‘artificial life’.<br />
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<td><h2>Define Patent...</h2><br />
When this 'creation' being seen as a patent and when is considered what sort of methods and genes are patented at this moment and judging the legal verdict about genetic patent cases, the extent to which the genetic patenting will play a role in research, seems limited. Since scientists, most of the time, try to comprehend and research natural phenomena, patent infringement should never occur; and that because natural genes and products can’t be patented. When engineers are researching a modified gene, they have to be able to see to what extent genetic licensing is done in that area. Until now this does not happen and for that reason the patent infringements come as an unwelcome surprise. Licensing for engineering purposes only seems fair, while the use of inventions has to be evaluated. <br />
When applications come to the market, and become more and more exposed to the society, the conflict against Genetic Modifications becomes high potential. When such applications have to be evaluated by a board, where all parties with their personal interests are present, a general acknowledgement of a certain application can be made.<br />
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<td> A patent on a gene is, however, allowable when one can show the inventive step. A smart way of the assembling matter is what an invention is and when a gene is rearranged to such an extent, that it has a new function which can now be credited. When this invention occurs in order to ease scientific findings, the latter have to pay for it. <br />
It has an analogy to transportation: Some people can’t buy a Mercedes. Mercedes cars are faster and provide ease, but there is always the possibility to walk. However, it really should be a non-obvious inventive step for experts too. A characteristic which in some patents can be doubted. </td><br />
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<h2> A spread of alternatives, a good idea?</h2><br />
The reaction of scientists to spread alternatives is, according to our opinion, great, and it speeds up the technological progression. Still people who do that, have to keep in mind, that their work is mostly funded by proven applications; thus they may be cutting in their own hands. <br/><br />
New inventions are a great matter, but that does not mean that they are also desired. Adjusting living species, a market-based estimation of value is not enough. The fact that people are willing to pay in order to gain something, does not meant that the desirable object is valuable. Commercial interests and interests of individuals involved, intended or unintended should be weighed. Individual target groups, prone to risks, should be informed and given a voice in the debate of implementing the application intended. This is the only way our desired world stays desired by everyone. <br />
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<h2>Putting interests on a balance... also not your own</h2><br />
And at this point the ethics factor takes place. Trying to co-live in this world with others, share the sources given to us with respect to ... the creator, the question whether creating new types of life prohibits any rights, is generated.<br />
For many years now religions all over the world implicate a belief in a spiritual world (often accompanied with a deity), influencing people's point of view and determining moral principles through a belief and/or cultural system. <br />
What religions often try to succeed is the explanatory world view, trying to grasp the world.<br />
<br/>Often religions consider living species being created for a reason (for instance, in the Catholic church the task of people is to make the world as if we live in heaven) and directing the insertion or deletion of functions, in these beings, tremendous effect. Most specificallt in our case, by the insertion of smelling genes in yeast, the whole sexual reproduction system of yeast is disturbed. The cause of reproduction therefore has been changed. Inserting designed genes in an organism, even taking the gradual discovery of essential functions into consideration, can be assumed ‘acting as God’ in the respect that there is a significant and directed influence in the target organism and its homologs.<br />
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<tr><td>Thus it is called to be considered: 'Where would it be permitted to implement such an invention?’ Additionally, the implementer has to wonder relatively to the possibility of dual use, being aware of consequences which can occur when the invention comes to open and much more considerations. The producer of the invention then has the ethical decision of distribution the invention. Given the ethical viewpoint of the inventor and regulator, he should be aware of the possible damages an invention may cause. It is the implementer that has to be blamed then, as such a product is sold to incapable people or people with malicious intentions.<br />
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<h2>A practical argument </h2><br><br />
According to knowledge relatively to evolutionary processes, it is known that many organisms modified in laboratories wouldn’t survive in nature. That simply lies to the fact that the ‘extra genes’ only cost extra energy and there is no gain in maintaining those genes. A yeast cell that has sacrificed its sexual reproduction mechanism to get the function of smelling, just would not survive. Changing species by knocking out functions or introducing extra survival skills however, can lead to more viable species. With these species the risk is greater and therefore the potential consequences, should be considered before their creation. What would it happen when such creator is realised in the nature? <br />
<br/>Natural virtue ethics is a part of virtue ethics theorem, that is discussed because it also considers the animalistic behavior of people. Being realistic, decision making doesn’t always go according to a theory, but mostly it occurs more pragmatic. When a decision is made it may contain someone’s moral point of view. This theory provides the proper characteristics of the righteous actor on which everyone should base their actions.<br />
Gene Modification seems a hard topic for a virtuous person or group. The topic provides a list of pros and cons, uncertainties and proven concepts, but when the act of gene transfer is righteous cannot be stated only by these facts. <br />
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<p>Together with the Rathenau Institute, our team organized one of the two debate rounds at the event Meeting of Young Minds. This debate took place on October 5h, the Friday of the Jamboree. The topic of this debate was about the release of research details on the creation of highly transmissible H5N1 (bird flu) in the lab. The expert who were invited to talk during this debate were Prof. Hans Westerhoff, an expert on synthetic biology from the VU Amsterdam, Dr. Koos van de Bruggen, from the workgroup biosecurity KNAW, Dr. Sander Herfst and Dr. Martin Linster, from the Erasmus MC who worked on the H5N1 research, Dr. Robin Pierce, expert on Law and regulations from the TU Delft, Pieter van Boheemen, iGEM 2010 alumnus and part of the Dutch Do-it-Yourself Biotechnology group and Mark Ruitenbeek, chairman of the VWS CDJA (a Dutch youth political party).With different experts we discussed 3 different statements: <br />
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• The NSABB made the right choice to give permission for publication of this research.<br />
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• Looking at the potential risks, this research should not have started in the first place.<br />
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• Scientific research may never be censored.<br />
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During this debate the public was asked to vote before and after each statement if they agreed or disagreed with the statement. It was very interesting to see that a few people did change their minds after they heard the discussion between the experts and our team.</br><br />
<br>The second round the iGEM team of UCL was hosting another debate about a future scenario disaster caused by synthetic bacteria that has mutated, which was also a very interesting debate. Those two debates were also judged by an independent jury, and have chosen our team as the WINNER of the MEETING OF YOUNG MINDS 2012!!!</br><br />
<br>To get an impression of the debate, click <a href="http://www.facebook.com/media/set/?set=a.477004565665846.114388.141853865847586&type=1" target="_blank">here </a></br><br />
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<h1>Ethical considerations during scientific investigation</h1> </td></tr><br />
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Our team had extra help from an embedded humanist, named Daan Schuurbiers, who followed the research as a midstream modulation project. Including Daan to the project, the team became also aware of the social sciences of the research. ‘’Midstream modulation asks how research is to be carried out, which is the main business of research, rather than whether a research project should be carried out, which is an upstream policy question. It is a means to evaluate and adjust research decisions in light of societal factors while the research process is taking place.’’ There are 3 different stages in the governance of science and technology, upstream, downstream and midstream modulation, see figure on the right. So by thinking about midstream modulation, this project is connected with the scientific research as well as to the social issues. In this documentary you will see how science will meet the human interest in many ways. <br />
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<h6>D. Schuurbiers, E. Fisher (2009), Lab-scale intervention. Science & Society Series on Convergence Research, EMBO reports VOL 10 NO 5</h6></p></td><br />
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Daan Schuurbiers is director of the Pilot Plant (De Proeffabriek), consultancy for responsible innovation. Daan studied chemistry and philosophy at the University of Amsterdam and has a PhD in ethics of technology from Delft University of Technology. His work centers on the social and ethical dimensions of newly emerging science and technologies. Daan's research efforts have focused on the design of new forms of dialogue between social and natural scientists, enhancing socio-ethical reflection in early stages of research. In addition to teaching and research, Daan has extensive experience in project management and consultancy, particularly in the area of dialogue and engagement with science and technology. <br />
He has published in academic journals as well as the popular press and has been involved in the organization of a range of teaching courses, master classes, competitions, workshops and other events throughout Europe. He now combines his writing, teaching, research and management skills in his work for the Pilot Plant, advising on ways to encourage reflection in research and to strengthen stakeholder engagement.<br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/EthicsTeam:TU-Delft/Ethics2012-10-26T17:31:49Z<p>Stephanielubbers: </p>
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<td colspan="2" align="left"><h1><br/>Snifferomyces Ethics</h1></td><br />
<tr><td colspan="2"><br />
Through our iGEM project we are called to create a Biobrick of a yeast detecting odors. This not only is part of Synthetic Biology and is therefore prone to ethical considerations, but also due to it's chimeric properties can be called an invention and therefore can be a potential patent target. The question generated is where the line should be placed between finding and investigation and thus the question is raised: Is a chimeric protein an invention?<br />
<br/><br><br />
To begin with and trying to define synthetic biology we come up with the deliberate design of biological systems and living organisms using engineering principles. Synthetic biology<br />
is the creation of ‘artificial life’.<br />
</td><br />
</tr><br />
<tr><br />
<td><h2>Define Patent...</h2><br />
When this 'creation' being seen as a patent and when is considered what sort of methods and genes are patented at this moment and judging the legal verdict about genetic patent cases, the extent to which the genetic patenting will play a role in research, seems limited. Since scientists, most of the time, try to comprehend and research natural phenomena, patent infringement should never occur; and that because natural genes and products can’t be patented. When engineers are researching a modified gene, they have to be able to see to what extent genetic licensing is done in that area. Until now this does not happen and for that reason the patent infringements come as an unwelcome surprise. Licensing for engineering purposes only seems fair, while the use of inventions has to be evaluated. <br />
When applications come to the market, and become more and more exposed to the society, the conflict against Genetic Modifications becomes high potential. When such applications have to be evaluated by a board, where all parties with their personal interests are present, a general acknowledgement of a certain application can be made.<br />
</td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/8/84/Gm_strawberries.jpg" width="140" height="180" align="right" valign="bottom"/></td><br />
</tr><br />
<tr><td colspan="2"><br />
<br />
</td></tr><br />
<tr><br />
<br />
<td> A patent on a gene is, however, allowable when one can show the inventive step. A smart way of the assembling matter is what an invention is and when a gene is rearranged to such an extent, that it has a new function which can now be credited. When this invention occurs in order to ease scientific findings, the latter have to pay for it. <br />
It has an analogy to transportation: Some people can’t buy a Mercedes. Mercedes cars are faster and provide ease, but there is always the possibility to walk. However, it really should be a non-obvious inventive step for experts too. A characteristic which in some patents can be doubted. </td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/1/14/Genengin.jpg" width="200" height="180" align="right" valign="bottom"/></td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<h2> A spread of alternatives, a good idea?</h2><br />
The reaction of scientists to spread alternatives is, according to our opinion, great, and it speeds up the technological progression. Still people who do that, have to keep in mind, that their work is mostly funded by proven applications; thus they may be cutting in their own hands. <br/><br />
New inventions are a great matter, but that does not mean that they are also desired. Adjusting living species, a market-based estimation of value is not enough. The fact that people are willing to pay in order to gain something, does not meant that the desirable object is valuable. Commercial interests and interests of individuals involved, intended or unintended should be weighed. Individual target groups, prone to risks, should be informed and given a voice in the debate of implementing the application intended. This is the only way our desired world stays desired by everyone. <br />
<br />
<br/><br />
<h2>Putting interests on a balance... also not your own</h2><br />
And at this point the ethics factor takes place. Trying to co-live in this world with others, share the sources given to us with respect to ... the creator, the question whether creating new types of life prohibits any rights, is generated.<br />
For many years now religions all over the world implicate a belief in a spiritual world (often accompanied with a deity), influencing people's point of view and determining moral principles through a belief and/or cultural system. <br />
What religions often try to succeed is the explanatory world view, trying to grasp the world.<br />
<br/>Often religions consider living species being created for a reason (for instance, in the Catholic church the task of people is to make the world as if we live in heaven) and directing the insertion or deletion of functions, in these beings, tremendous effect. Most specificallt in our case, by the insertion of smelling genes in yeast, the whole sexual reproduction system of yeast is disturbed. The cause of reproduction therefore has been changed. Inserting designed genes in an organism, even taking the gradual discovery of essential functions into consideration, can be assumed ‘acting as God’ in the respect that there is a significant and directed influence in the target organism and its homologs.<br />
</td><br />
</tr><br />
<tr><td>Thus it is called to be considered: 'Where would it be permitted to implement such an invention?’ Additionally, the implementer has to wonder relatively to the possibility of dual use, being aware of consequences which can occur when the invention comes to open and much more considerations. The producer of the invention then has the ethical decision of distribution the invention. Given the ethical viewpoint of the inventor and regulator, he should be aware of the possible damages an invention may cause. It is the implementer that has to be blamed then, as such a product is sold to incapable people or people with malicious intentions.<br />
</td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/e/ee/Apples.jpg" width="200" height="260" align="right" valign="bottom"/></td><br />
</tr><br />
<tr><td colspan="2"><br />
<h2>A practical argument </h2><br><br />
According to knowledge relatively to evolutionary processes, it is known that many organisms modified in laboratories wouldn’t survive in nature. That simply lies to the fact that the ‘extra genes’ only cost extra energy and there is no gain in maintaining those genes. A yeast cell that has sacrificed its sexual reproduction mechanism to get the function of smelling, just would not survive. Changing species by knocking out functions or introducing extra survival skills however, can lead to more viable species. With these species the risk is greater and therefore the potential consequences, should be considered before their creation. What would it happen when such creator is realised in the nature? <br />
<br/>Natural virtue ethics is a part of virtue ethics theorem, that is discussed because it also considers the animalistic behavior of people. Being realistic, decision making doesn’t always go according to a theory, but mostly it occurs more pragmatic. When a decision is made it may contain someone’s moral point of view. This theory provides the proper characteristics of the righteous actor on which everyone should base their actions.<br />
Gene Modification seems a hard topic for a virtuous person or group. The topic provides a list of pros and cons, uncertainties and proven concepts, but when the act of gene transfer is righteous cannot be stated only by these facts. <br />
<br />
</td></tr></table><br />
<table width="100%" > <br />
<tr><br />
<td colspan="2" align="left"><h1><br/>Meeting of Young Minds</h1><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<p>Together with the Rathenau Institute, our team organized one of the two debate rounds at the event Meeting of Young Minds. This debate took place on October 5h, the Friday of the Jamboree. The topic of this debate was about the release of research details on the creation of highly transmissible H5N1 (bird flu) in the lab. The expert who were invited to talk during this debate were Prof. Hans Westerhoff, an expert on synthetic biology from the VU Amsterdam, Dr. Koos van de Bruggen, from the workgroup biosecurity KNAW, Dr. Sander Herfst and Dr. Martin Linster, from the Erasmus MC who worked on the H5N1 research, Dr. Robin Pierce, expert on Law and regulations from the TU Delft, Pieter van Boheemen, iGEM 2010 alumnus and part of the Dutch Do-it-Yourself Biotechnology group and Mark Ruitenbeek, chairman of the VWS CDJA (a Dutch youth political party).With different experts we discussed 3 different statements: <br />
<br/><br />
<br/><br />
• The NSABB made the right choice to give permission for publication of this research.<br />
<br/><br />
• Looking at the potential risks, this research should not have started in the first place.<br />
<br/><br />
• Scientific research may never be censored.<br />
<br/><br />
<br/><br />
During this debate the public was asked to vote before and after each statement if they agreed or disagreed with the statement. It was very interesting to see that a few people did change their minds after they heard the discussion between the experts and our team.<br />
<br>The second round the iGEM team of UCL was hosting another debate about a future scenario disaster caused by synthetic bacteria that has mutated, which was also a very interesting debate. Those two debates were also judged by an independent jury, and have chosen our team as the WINNER of the MEETING OF YOUNG MINDS 2012!!!</br><br />
<br>To get an impression of the debate, click <a href="http://www.facebook.com/media/set/?set=a.477004565665846.114388.141853865847586&type=1" target="_blank">here </a></br><br />
</p><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br/><br />
<h1>Ethical considerations during scientific investigation</h1> </td></tr><br />
<tr><td><p><br />
Our team had extra help from an embedded humanist, named Daan Schuurbiers, who followed the research as a midstream modulation project. Including Daan to the project, the team became also aware of the social sciences of the research. ‘’Midstream modulation asks how research is to be carried out, which is the main business of research, rather than whether a research project should be carried out, which is an upstream policy question. It is a means to evaluate and adjust research decisions in light of societal factors while the research process is taking place.’’ There are 3 different stages in the governance of science and technology, upstream, downstream and midstream modulation, see figure on the right. So by thinking about midstream modulation, this project is connected with the scientific research as well as to the social issues. In this documentary you will see how science will meet the human interest in many ways. <br />
<br/><br />
<h6>D. Schuurbiers, E. Fisher (2009), Lab-scale intervention. Science & Society Series on Convergence Research, EMBO reports VOL 10 NO 5</h6></p></td><br />
<td><a href="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" target="_blank"><img src="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" width="140" height="180" align="right" valign="bottom" /></a></td><br />
</tr><br />
</table><br />
<br/><br />
<table width="100%" ><br />
<tr><br />
<td colspan="2" align="left"><h3><br/>Who is Daan Schuurbiers? – Our embedded humanist</h3></td><br />
<br />
<tr><br />
<br />
<td><br />
<p><br />
Daan Schuurbiers is director of the Pilot Plant (De Proeffabriek), consultancy for responsible innovation. Daan studied chemistry and philosophy at the University of Amsterdam and has a PhD in ethics of technology from Delft University of Technology. His work centers on the social and ethical dimensions of newly emerging science and technologies. Daan's research efforts have focused on the design of new forms of dialogue between social and natural scientists, enhancing socio-ethical reflection in early stages of research. In addition to teaching and research, Daan has extensive experience in project management and consultancy, particularly in the area of dialogue and engagement with science and technology. <br />
He has published in academic journals as well as the popular press and has been involved in the organization of a range of teaching courses, master classes, competitions, workshops and other events throughout Europe. He now combines his writing, teaching, research and management skills in his work for the Pilot Plant, advising on ways to encourage reflection in research and to strengthen stakeholder engagement.<br />
</p></td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/1/17/Daan.png" width="140" height="180" align="right" valign="bottom"/></td><br />
</tr><br />
</table><br />
<br />
<br />
<br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' height=140 width=195 /></a></td><br />
</tr></table><br />
</center><br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/EthicsTeam:TU-Delft/Ethics2012-10-26T17:29:38Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Ethics</title><br />
<body> <br />
<div style="height:70px; width:100%;"></div><br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
<br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ea/Ethics.jpg" align="middle" width="100%"><br />
<center><br />
<br />
<table width="100%" align="justify"> <br />
<td colspan="2" align="left"><h1><br/>Snifferomyces Ethics</h1></td><br />
<tr><td colspan="2"><br />
Through our iGEM project we are called to create a Biobrick of a yeast detecting odors. This not only is part of Synthetic Biology and is therefore prone to ethical considerations, but also due to it's chimeric properties can be called an invention and therefore can be a potential patent target. The question generated is where the line should be placed between finding and investigation and thus the question is raised: Is a chimeric protein an invention?<br />
<br/><br><br />
To begin with and trying to define synthetic biology we come up with the deliberate design of biological systems and living organisms using engineering principles. Synthetic biology<br />
is the creation of ‘artificial life’.<br />
</td><br />
</tr><br />
<tr><br />
<td><h2>Define Patent...</h2><br />
When this 'creation' being seen as a patent and when is considered what sort of methods and genes are patented at this moment and judging the legal verdict about genetic patent cases, the extent to which the genetic patenting will play a role in research, seems limited. Since scientists, most of the time, try to comprehend and research natural phenomena, patent infringement should never occur; and that because natural genes and products can’t be patented. When engineers are researching a modified gene, they have to be able to see to what extent genetic licensing is done in that area. Until now this does not happen and for that reason the patent infringements come as an unwelcome surprise. Licensing for engineering purposes only seems fair, while the use of inventions has to be evaluated. <br />
When applications come to the market, and become more and more exposed to the society, the conflict against Genetic Modifications becomes high potential. When such applications have to be evaluated by a board, where all parties with their personal interests are present, a general acknowledgement of a certain application can be made.<br />
</td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/8/84/Gm_strawberries.jpg" width="140" height="180" align="right" valign="bottom"/></td><br />
</tr><br />
<tr><td colspan="2"><br />
<br />
</td></tr><br />
<tr><br />
<br />
<td> A patent on a gene is, however, allowable when one can show the inventive step. A smart way of the assembling matter is what an invention is and when a gene is rearranged to such an extent, that it has a new function which can now be credited. When this invention occurs in order to ease scientific findings, the latter have to pay for it. <br />
It has an analogy to transportation: Some people can’t buy a Mercedes. Mercedes cars are faster and provide ease, but there is always the possibility to walk. However, it really should be a non-obvious inventive step for experts too. A characteristic which in some patents can be doubted. </td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/1/14/Genengin.jpg" width="200" height="180" align="right" valign="bottom"/></td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<h2> A spread of alternatives, a good idea?</h2><br />
The reaction of scientists to spread alternatives is, according to our opinion, great, and it speeds up the technological progression. Still people who do that, have to keep in mind, that their work is mostly funded by proven applications; thus they may be cutting in their own hands. <br/><br />
New inventions are a great matter, but that does not mean that they are also desired. Adjusting living species, a market-based estimation of value is not enough. The fact that people are willing to pay in order to gain something, does not meant that the desirable object is valuable. Commercial interests and interests of individuals involved, intended or unintended should be weighed. Individual target groups, prone to risks, should be informed and given a voice in the debate of implementing the application intended. This is the only way our desired world stays desired by everyone. <br />
<br />
<br/><br />
<h2>Putting interests on a balance... also not your own</h2><br />
And at this point the ethics factor takes place. Trying to co-live in this world with others, share the sources given to us with respect to ... the creator, the question whether creating new types of life prohibits any rights, is generated.<br />
For many years now religions all over the world implicate a belief in a spiritual world (often accompanied with a deity), influencing people's point of view and determining moral principles through a belief and/or cultural system. <br />
What religions often try to succeed is the explanatory world view, trying to grasp the world.<br />
<br/>Often religions consider living species being created for a reason (for instance, in the Catholic church the task of people is to make the world as if we live in heaven) and directing the insertion or deletion of functions, in these beings, tremendous effect. Most specificallt in our case, by the insertion of smelling genes in yeast, the whole sexual reproduction system of yeast is disturbed. The cause of reproduction therefore has been changed. Inserting designed genes in an organism, even taking the gradual discovery of essential functions into consideration, can be assumed ‘acting as God’ in the respect that there is a significant and directed influence in the target organism and its homologs.<br />
</td><br />
</tr><br />
<tr><td>Thus it is called to be considered: 'Where would it be permitted to implement such an invention?’ Additionally, the implementer has to wonder relatively to the possibility of dual use, being aware of consequences which can occur when the invention comes to open and much more considerations. The producer of the invention then has the ethical decision of distribution the invention. Given the ethical viewpoint of the inventor and regulator, he should be aware of the possible damages an invention may cause. It is the implementer that has to be blamed then, as such a product is sold to incapable people or people with malicious intentions.<br />
</td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/e/ee/Apples.jpg" width="200" height="260" align="right" valign="bottom"/></td><br />
</tr><br />
<tr><td colspan="2"><br />
<h2>A practical argument </h2><br><br />
According to knowledge relatively to evolutionary processes, it is known that many organisms modified in laboratories wouldn’t survive in nature. That simply lies to the fact that the ‘extra genes’ only cost extra energy and there is no gain in maintaining those genes. A yeast cell that has sacrificed its sexual reproduction mechanism to get the function of smelling, just would not survive. Changing species by knocking out functions or introducing extra survival skills however, can lead to more viable species. With these species the risk is greater and therefore the potential consequences, should be considered before their creation. What would it happen when such creator is realised in the nature? <br />
<br/>Natural virtue ethics is a part of virtue ethics theorem, that is discussed because it also considers the animalistic behavior of people. Being realistic, decision making doesn’t always go according to a theory, but mostly it occurs more pragmatic. When a decision is made it may contain someone’s moral point of view. This theory provides the proper characteristics of the righteous actor on which everyone should base their actions.<br />
Gene Modification seems a hard topic for a virtuous person or group. The topic provides a list of pros and cons, uncertainties and proven concepts, but when the act of gene transfer is righteous cannot be stated only by these facts. <br />
<br />
</td></tr></table><br />
<table width="100%" > <br />
<tr><br />
<td colspan="2" align="left"><h1><br/>Meeting of Young Minds</h1><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<p>Together with the Rathenau Institute, our team organized one of the two debate rounds at the event Meeting of Young Minds. This debate took place on October 5h, the Friday of the Jamboree. The topic of this debate was about the release of research details on the creation of highly transmissible H5N1 (bird flu) in the lab. The expert who were invited to talk during this debate were Prof. Hans Westerhoff, an expert on synthetic biology from the VU Amsterdam, Dr. Koos van de Bruggen, from the workgroup biosecurity KNAW, Dr. Sander Herfst and Dr. Martin Linster, from the Erasmus MC who worked on the H5N1 research, Dr. Robin Pierce, expert on Law and regulations from the TU Delft, Pieter van Boheemen, iGEM 2010 alumnus and part of the Dutch Do-it-Yourself Biotechnology group and Mark Ruitenbeek, chairman of the VWS CDJA (a Dutch youth political party).With different experts we discussed 3 different statements: <br />
<br/><br />
<br/><br />
• The NSABB made the right choice to give permission for publication of this research.<br />
<br/><br />
• Looking at the potential risks, this research should not have started in the first place.<br />
<br/><br />
• Scientific research may never be censored.<br />
<br/><br />
<br/><br />
During this debate the public was asked to vote before and after each statement if they agreed or disagreed with the statement. It was very interesting to see that a few people did change their minds after they heard the discussion between the experts and our team.<br />
<br>The second round the iGEM team of UCL was hosting another debate about a future scenario disaster caused by synthetic bacteria that has mutated, which was also a very interesting debate. Those two debates were also judged by an independent jury, and have chosen our team as the WINNER of the MEETING OF YOUNG MINDS 2012!!!</br><br />
<br>To get an impression of the debate, click http://www.facebook.com/media/set/?set=a.477004565665846.114388.141853865847586&type=1</br><br />
</p><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br/><br />
<h1>Ethical considerations during scientific investigation</h1> </td></tr><br />
<tr><td><p><br />
Our team had extra help from an embedded humanist, named Daan Schuurbiers, who followed the research as a midstream modulation project. Including Daan to the project, the team became also aware of the social sciences of the research. ‘’Midstream modulation asks how research is to be carried out, which is the main business of research, rather than whether a research project should be carried out, which is an upstream policy question. It is a means to evaluate and adjust research decisions in light of societal factors while the research process is taking place.’’ There are 3 different stages in the governance of science and technology, upstream, downstream and midstream modulation, see figure on the right. So by thinking about midstream modulation, this project is connected with the scientific research as well as to the social issues. In this documentary you will see how science will meet the human interest in many ways. <br />
<br/><br />
<h6>D. Schuurbiers, E. Fisher (2009), Lab-scale intervention. Science & Society Series on Convergence Research, EMBO reports VOL 10 NO 5</h6></p></td><br />
<td><a href="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" target="_blank"><img src="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" width="140" height="180" align="right" valign="bottom" /></a></td><br />
</tr><br />
</table><br />
<br/><br />
<table width="100%" ><br />
<tr><br />
<td colspan="2" align="left"><h3><br/>Who is Daan Schuurbiers? – Our embedded humanist</h3></td><br />
<br />
<tr><br />
<br />
<td><br />
<p><br />
Daan Schuurbiers is director of the Pilot Plant (De Proeffabriek), consultancy for responsible innovation. Daan studied chemistry and philosophy at the University of Amsterdam and has a PhD in ethics of technology from Delft University of Technology. His work centers on the social and ethical dimensions of newly emerging science and technologies. Daan's research efforts have focused on the design of new forms of dialogue between social and natural scientists, enhancing socio-ethical reflection in early stages of research. In addition to teaching and research, Daan has extensive experience in project management and consultancy, particularly in the area of dialogue and engagement with science and technology. <br />
He has published in academic journals as well as the popular press and has been involved in the organization of a range of teaching courses, master classes, competitions, workshops and other events throughout Europe. He now combines his writing, teaching, research and management skills in his work for the Pilot Plant, advising on ways to encourage reflection in research and to strengthen stakeholder engagement.<br />
</p></td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/1/17/Daan.png" width="140" height="180" align="right" valign="bottom"/></td><br />
</tr><br />
</table><br />
<br />
<br />
<br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' height=140 width=195 /></a></td><br />
</tr></table><br />
</center><br />
</div><br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/EthicsTeam:TU-Delft/Ethics2012-10-26T17:20:27Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Ethics</title><br />
<body> <br />
<div style="height:70px; width:100%;"></div><br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<div id="contentbox" style="text-align:justify;"><br />
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<img src="https://static.igem.org/mediawiki/igem.org/e/ea/Ethics.jpg" align="middle" width="100%"><br />
<center><br />
<br />
<table width="100%" align="justify"> <br />
<td colspan="2" align="left"><h1><br/>Snifferomyces Ethics</h1></td><br />
<tr><td colspan="2"><br />
Through our iGEM project we are called to create a Biobrick of a yeast detecting odors. This not only is part of Synthetic Biology and is therefore prone to ethical considerations, but also due to it's chimeric properties can be called an invention and therefore can be a potential patent target. The question generated is where the line should be placed between finding and investigation and thus the question is raised: Is a chimeric protein an invention?<br />
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To begin with and trying to define synthetic biology we come up with the deliberate design of biological systems and living organisms using engineering principles. Synthetic biology<br />
is the creation of ‘artificial life’.<br />
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<td><h2>Define Patent...</h2><br />
When this 'creation' being seen as a patent and when is considered what sort of methods and genes are patented at this moment and judging the legal verdict about genetic patent cases, the extent to which the genetic patenting will play a role in research, seems limited. Since scientists, most of the time, try to comprehend and research natural phenomena, patent infringement should never occur; and that because natural genes and products can’t be patented. When engineers are researching a modified gene, they have to be able to see to what extent genetic licensing is done in that area. Until now this does not happen and for that reason the patent infringements come as an unwelcome surprise. Licensing for engineering purposes only seems fair, while the use of inventions has to be evaluated. <br />
When applications come to the market, and become more and more exposed to the society, the conflict against Genetic Modifications becomes high potential. When such applications have to be evaluated by a board, where all parties with their personal interests are present, a general acknowledgement of a certain application can be made.<br />
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<td> A patent on a gene is, however, allowable when one can show the inventive step. A smart way of the assembling matter is what an invention is and when a gene is rearranged to such an extent, that it has a new function which can now be credited. When this invention occurs in order to ease scientific findings, the latter have to pay for it. <br />
It has an analogy to transportation: Some people can’t buy a Mercedes. Mercedes cars are faster and provide ease, but there is always the possibility to walk. However, it really should be a non-obvious inventive step for experts too. A characteristic which in some patents can be doubted. </td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/1/14/Genengin.jpg" width="200" height="180" align="right" valign="bottom"/></td><br />
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<h2> A spread of alternatives, a good idea?</h2><br />
The reaction of scientists to spread alternatives is, according to our opinion, great, and it speeds up the technological progression. Still people who do that, have to keep in mind, that their work is mostly funded by proven applications; thus they may be cutting in their own hands. <br/><br />
New inventions are a great matter, but that does not mean that they are also desired. Adjusting living species, a market-based estimation of value is not enough. The fact that people are willing to pay in order to gain something, does not meant that the desirable object is valuable. Commercial interests and interests of individuals involved, intended or unintended should be weighed. Individual target groups, prone to risks, should be informed and given a voice in the debate of implementing the application intended. This is the only way our desired world stays desired by everyone. <br />
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<h2>Putting interests on a balance... also not your own</h2><br />
And at this point the ethics factor takes place. Trying to co-live in this world with others, share the sources given to us with respect to ... the creator, the question whether creating new types of life prohibits any rights, is generated.<br />
For many years now religions all over the world implicate a belief in a spiritual world (often accompanied with a deity), influencing people's point of view and determining moral principles through a belief and/or cultural system. <br />
What religions often try to succeed is the explanatory world view, trying to grasp the world.<br />
<br/>Often religions consider living species being created for a reason (for instance, in the Catholic church the task of people is to make the world as if we live in heaven) and directing the insertion or deletion of functions, in these beings, tremendous effect. Most specificallt in our case, by the insertion of smelling genes in yeast, the whole sexual reproduction system of yeast is disturbed. The cause of reproduction therefore has been changed. Inserting designed genes in an organism, even taking the gradual discovery of essential functions into consideration, can be assumed ‘acting as God’ in the respect that there is a significant and directed influence in the target organism and its homologs.<br />
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<tr><td>Thus it is called to be considered: 'Where would it be permitted to implement such an invention?’ Additionally, the implementer has to wonder relatively to the possibility of dual use, being aware of consequences which can occur when the invention comes to open and much more considerations. The producer of the invention then has the ethical decision of distribution the invention. Given the ethical viewpoint of the inventor and regulator, he should be aware of the possible damages an invention may cause. It is the implementer that has to be blamed then, as such a product is sold to incapable people or people with malicious intentions.<br />
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<h2>A practical argument </h2><br><br />
According to knowledge relatively to evolutionary processes, it is known that many organisms modified in laboratories wouldn’t survive in nature. That simply lies to the fact that the ‘extra genes’ only cost extra energy and there is no gain in maintaining those genes. A yeast cell that has sacrificed its sexual reproduction mechanism to get the function of smelling, just would not survive. Changing species by knocking out functions or introducing extra survival skills however, can lead to more viable species. With these species the risk is greater and therefore the potential consequences, should be considered before their creation. What would it happen when such creator is realised in the nature? <br />
<br/>Natural virtue ethics is a part of virtue ethics theorem, that is discussed because it also considers the animalistic behavior of people. Being realistic, decision making doesn’t always go according to a theory, but mostly it occurs more pragmatic. When a decision is made it may contain someone’s moral point of view. This theory provides the proper characteristics of the righteous actor on which everyone should base their actions.<br />
Gene Modification seems a hard topic for a virtuous person or group. The topic provides a list of pros and cons, uncertainties and proven concepts, but when the act of gene transfer is righteous cannot be stated only by these facts. <br />
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<p>Together with the Rathenau Institute, our team organized one of the two debate rounds at the event Meeting of Young Minds. This debate took place on October 5h, the Friday of the Jamboree. The topic of this debate was about the release of research details on the creation of highly transmissible H5N1 (bird flu) in the lab. The expert who were invited to talk during this debate were Prof. Hans Westerhoff, an expert on synthetic biology from the VU Amsterdam, Dr. Koos van de Bruggen, from the workgroup biosecurity KNAW, Dr. Sander Herfst and Dr. Martin Linster, from the Erasmus MC who worked on the H5N1 research, Dr. Robin Pierce, expert on Law and regulations from the TU Delft, Pieter van Boheemen, iGEM 2010 alumnus and part of the Dutch Do-it-Yourself Biotechnology group and Mark Ruitenbeek, chairman of the VWS CDJA (a Dutch youth political party).With different experts we discussed 3 different statements: <br />
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• The NSABB made the right choice to give permission for publication of this research.<br />
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• Looking at the potential risks, this research should not have started in the first place.<br />
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• Scientific research may never be censored.<br />
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During this debate the public was asked to vote before and after each statement if they agreed or disagreed with the statement. It was very interesting to see that a few people did change their minds after they heard the discussion between the experts and our team.<br />
<br>The second round the iGEM team of UCL was hosting another debate about a future scenario disaster caused by synthetic bacteria that has mutated, which was also a very interesting debate. Those two debates were also judged by an independent jury, and have chosen our team as the WINNER of the MEETING OF YOUNG MINDS 2012!!!</br><br />
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<h1>Ethical considerations during scientific investigation</h1> </td></tr><br />
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Our team had extra help from an embedded humanist, named Daan Schuurbiers, who followed the research as a midstream modulation project. Including Daan to the project, the team became also aware of the social sciences of the research. ‘’Midstream modulation asks how research is to be carried out, which is the main business of research, rather than whether a research project should be carried out, which is an upstream policy question. It is a means to evaluate and adjust research decisions in light of societal factors while the research process is taking place.’’ There are 3 different stages in the governance of science and technology, upstream, downstream and midstream modulation, see figure on the right. So by thinking about midstream modulation, this project is connected with the scientific research as well as to the social issues. In this documentary you will see how science will meet the human interest in many ways. <br />
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<h6>D. Schuurbiers, E. Fisher (2009), Lab-scale intervention. Science & Society Series on Convergence Research, EMBO reports VOL 10 NO 5</h6></p></td><br />
<td><a href="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" target="_blank"><img src="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" width="140" height="180" align="right" valign="bottom" /></a></td><br />
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<td colspan="2" align="left"><h3><br/>Who is Daan Schuurbiers? – Our embedded humanist</h3></td><br />
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Daan Schuurbiers is director of the Pilot Plant (De Proeffabriek), consultancy for responsible innovation. Daan studied chemistry and philosophy at the University of Amsterdam and has a PhD in ethics of technology from Delft University of Technology. His work centers on the social and ethical dimensions of newly emerging science and technologies. Daan's research efforts have focused on the design of new forms of dialogue between social and natural scientists, enhancing socio-ethical reflection in early stages of research. In addition to teaching and research, Daan has extensive experience in project management and consultancy, particularly in the area of dialogue and engagement with science and technology. <br />
He has published in academic journals as well as the popular press and has been involved in the organization of a range of teaching courses, master classes, competitions, workshops and other events throughout Europe. He now combines his writing, teaching, research and management skills in his work for the Pilot Plant, advising on ways to encourage reflection in research and to strengthen stakeholder engagement.<br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-10-26T15:04:19Z<p>Stephanielubbers: </p>
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<h2>Snifferomyces - A Tuberculosis Screening Automaton</h2><br><br />
<p> What is the use of technology, if it cannot contribute to improving human life? With this thought in mind, the TU Delft 2012 iGEM team, composed of students from the life sciences, bioinformatics, applied physics, aerospace, maritime, mechanical and chemical engineering disciplines decided to use the platform of synthetic biology, addressing a real challenge affecting millions of people .<br />
<br/><br />
Inspired by the sniffer rats trained to smell the presence of tuberculosis, the team decided to build an autonomous olfactory system to detect volatile compounds, by re-inventing man's oldest industrial microorganism, yeast, to provide for a non-invasive, rapid and cost-effective diagnosis system for tuberculosis. The reason why we have chosen for yeast, is that yeast is relative cheap to grow. Furthermore yeast has the ability to sense low amounts of concentration of specific compounds and can be storage for a long time.</p><br />
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<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
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<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
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<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
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<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
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<h3>Our ideal Solution</h3><br />
<p>A cheap test that quickly gives an reliable result, that can be taken by a 4x4 car to the people.</p><br />
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<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Remote areas can be easily reached. <br />
</br><h6>Evaluating of test result</h6>Now we did the tests with GFP but if would use a visible output, it would be very easy to see a result. Which also mean that there are not many facilities needed.<br />
</br><h6>Cheap</h6>The producing of a large amount of yeast cells is in general not this expensive.<br />
</br><h6>Reliability</h6> This is something that should still be evaluated.<br />
</br><h6>Waiting time</h6> The waiting time for the result will be approximately 3 hours.</p><br />
<h3>Conclusion</h3> <br />
<p>We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.</p><br />
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<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
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<br><h2> Possible applications of the Sniffer-O-Meter!</h2> </br><br />
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<h3> The Royal Dutch Military Police regarding a detector of explosives. </h3><br />
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<p>Every day, 1800 member of the Royal Dutch Military Police are present at Schiphol to detect possible threats to the National Security. One part of their job is to be on the lookout for explosives. <b>This is where smell plays an important part! </b> Explosives are usually detected by Explo-dogs, dogs which have been trained to detect the scent associated with explosives. <br />
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<img src="https://static.igem.org/mediawiki/igem.org/6/69/Explohond.jpg" width="600"/><br />
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An Explo-Dog is being trained to detect 14 different types of smells, which for security reasons will not be mentioned, in different combinations. The largest amount of explosives are covered by this intensive training after which they will work together with a canine trainer of the Military Police, such as Rick van Vulpen who spoke to us on this matter. <br/><br />
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<b>A Sniffer-O-Meter could be made to smell these same 14 volatiles and to give a signal dependent on what combination of volatiles is detected.</b> The Snifferomyces is designed to be a general platform for any possible smell, smelling explosives is only one of the possible applications. The Sniffer-O-Meter could be redesigned to be carried around or to stay at a central position, like a fire detector. <br/><br />
<br/><br />
<b>"Micro-organisms and GMOs would definitely be used if it would improve the National Security." </b><br/><br />
The most important feature should be a very low number of false positives. It is a waste when the team responds to a false alarm, this costs a lot of time and money. Genetic modification is a new, important technology which, when whithin certain safety standards should definitely be used. At the moment we are experimenting with a chemical 'Nose', but this technology also responds to coca-cola, which has caused a lot of false alarms. In the lab a small error rate might be seen as acceptable, but in the field this is less so. <br/><br />
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On the job, dog and trainer work together as coworkers. And even though canine is trained to smell, his secundary role is to give a secure feeling to the crowd at an airport and the trainer. Of course this role would never be replaced by micro-organisms, although they could prove to become a solid addition to the general equipment. </p><br/><br />
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We would like to thank Rick van Vulpen for a nice chat on this subject! <br/><br />
The picture is from "Safety and Security", October 2012, a supplement of the Telegraaf.<br/><br />
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<br/><h3>Talk with Dr. Lutter about the applicability of our research within the medical field </h3><br />
To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter ( is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. </br><br />
<br/>Has we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably eventually lead up to a new detection method in the medical field. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/><b>Intensive care </b><br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br><b>Resistant TB </b><br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/><b>HIV and TB</b> <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/><b>Fact:</b><i> From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB.</i><br />
<a href="http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx">www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx</a> <br/><br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. And we would like to thank Dr. Rene Lutter for his input in our project! <br/> </div><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-10-26T15:03:04Z<p>Stephanielubbers: </p>
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<h2>Snifferomyces - A Tuberculosis Screening Automaton</h2><br><br />
<p> What is the use of technology, if it cannot contribute to improving human life? With this thought in mind, the TU Delft 2012 iGEM team, composed of students from the life sciences, bioinformatics, applied physics, aerospace, maritime, mechanical and chemical engineering disciplines decided to use the platform of synthetic biology, addressing a real challenge affecting millions of people .<br />
<br/><br />
Inspired by the sniffer rats trained to smell the presence of tuberculosis, the team decided to build an autonomous olfactory system to detect volatile compounds, by re-inventing man's oldest industrial microorganism, yeast, to provide for a non-invasive, rapid and cost-effective diagnosis system for tuberculosis. The reason why we have chosen for yeast, is that yeast is relative cheap to grow. Furthermore yeast has the ability to sense low amounts of concentration of specific compounds and can be storage for a long time.</p><br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>A cheap test that quickly gives an reliable result, that can be taken by a 4x4 car to the people.</p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Remote areas can be easily reached. <br />
</br><h6>Evaluating of test result</h6>Now we did the tests with GFP but if would use a visible output, it would be very easy to see a result. Which also mean that there are not many facilities needed.<br />
</br><h6>Cheap</h6>The producing of a large amount of yeast cells is in general not this expensive.<br />
</br><h6>Reliability</h6> This is something that should still be evaluated.<br />
</br><h6>Waiting time</h6> The waiting time for the result will be approximately 3 hours.</p><br />
<h3>Conclusion</h3> <br />
<p>We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<br />
<br><h2> Possible applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<h3> The Royal Dutch Military Police regarding a detector of explosives. </h3><br />
<br />
<p>Every day, 1800 member of the Royal Dutch Military Police are present at Schiphol to detect possible threats to the National Security. One part of their job is to be on the lookout for explosives. <b>This is where smell plays an important part! </b> Explosives are usually detected by Explo-dogs, dogs which have been trained to detect the scent associated with explosives. <br />
<br/><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/6/69/Explohond.jpg" width="600"/><br />
<br/><br />
<br />
An Explo-Dog is being trained to detect 14 different types of smells, which for security reasons will not be mentioned, in different combinations. The largest amount of explosives are covered by this intensive training after which they will work together with a canine trainer of the Military Police, such as Rick van Vulpen who spoke to us on this matter. <br/><br />
<br/><br />
<br />
<b>A Sniffer-O-Meter could be made to smell these same 14 volatiles and to give a signal dependent on what combination of volatiles is detected.</b> The Snifferomyces is designed to be a general platform for any possible smell, smelling explosives is only one of the possible applications. The Sniffer-O-Meter could be redesigned to be carried around or to stay at a central position, like a fire detector. <br/><br />
<br/><br />
<b>"Micro-organisms and GMOs would definitely be used if it would improve the National Security." </b><br/><br />
The most important feature should be a very low number of false positives. It is a waste when the team responds to a false alarm, this costs a lot of time and money. Genetic modification is a new, important technology which, when whithin certain safety standards should definitely be used. At the moment we are experimenting with a chemical 'Nose', but this technology also responds to coca-cola, which has caused a lot of false alarms. In the lab a small error rate might be seen as acceptable, but in the field this is less so. <br/><br />
<br/><br />
On the job, dog and trainer work together as coworkers. And even though canine is trained to smell, his secundary role is to give a secure feeling to the crowd at an airport and the trainer. Of course this role would never be replaced by micro-organisms, although they could prove to become a solid addition to the general equipment. </p><br/><br />
<br/><br />
We would like to thank Rick van Vulpen for a nice chat on this subject! <br/><br />
The picture is from "Safety and Security", October 2012, a supplement of the Telegraaf.<br/><br />
<br />
<br/><h3>Talk with Dr. Lutter about the applicability of our research within the medical field </h3><br />
To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter ( is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. </br><br />
<br/>Has we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably eventually lead up to a new detection method in the medical field. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/><b>Intensive care </b><br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br><b>Resistant TB </b><br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/><b>HIV and TB</b> <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/><b>Fact:</b><i> From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB.</i> <a href="http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx">www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx</a> <br/><br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. And we would like to thank Dr. Rene Lutter for his input in our project! <br/> </div><br />
<br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-10-26T15:01:26Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<br />
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<br />
<br />
<br />
<h2>Snifferomyces - A Tuberculosis Screening Automaton</h2><br><br />
<p> What is the use of technology, if it cannot contribute to improving human life? With this thought in mind, the TU Delft 2012 iGEM team, composed of students from the life sciences, bioinformatics, applied physics, aerospace, maritime, mechanical and chemical engineering disciplines decided to use the platform of synthetic biology, addressing a real challenge affecting millions of people .<br />
<br/><br />
Inspired by the sniffer rats trained to smell the presence of tuberculosis, the team decided to build an autonomous olfactory system to detect volatile compounds, by re-inventing man's oldest industrial microorganism, yeast, to provide for a non-invasive, rapid and cost-effective diagnosis system for tuberculosis. The reason why we have chosen for yeast, is that yeast is relative cheap to grow. Furthermore yeast has the ability to sense low amounts of concentration of specific compounds and can be storage for a long time.</p><br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>A cheap test that quickly gives an reliable result, that can be taken by a 4x4 car to the people.</p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Remote areas can be easily reached. <br />
</br><h6>Evaluating of test result</h6>Now we did the tests with GFP but if would use a visible output, it would be very easy to see a result. Which also mean that there are not many facilities needed.<br />
</br><h6>Cheap</h6>The producing of a large amount of yeast cells is in general not this expensive.<br />
</br><h6>Reliability</h6> This is something that should still be evaluated.<br />
</br><h6>Waiting time</h6> The waiting time for the result will be approximately 3 hours.</p><br />
<h3>Conclusion</h3> <br />
<p>We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<br />
<br><h2> Possible applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<h3> The Royal Dutch Military Police regarding a detector of explosives. </h3><br />
<br />
<p>Every day, 1800 member of the Royal Dutch Military Police are present at Schiphol to detect possible threats to the National Security. One part of their job is to be on the lookout for explosives. <b>This is where smell plays an important part! </b> Explosives are usually detected by Explo-dogs, dogs which have been trained to detect the scent associated with explosives. <br />
<br/><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/6/69/Explohond.jpg" width="600"/><br />
<br/><br />
<br />
An Explo-Dog is being trained to detect 14 different types of smells, which for security reasons will not be mentioned, in different combinations. The largest amount of explosives are covered by this intensive training after which they will work together with a canine trainer of the Military Police, such as Rick van Vulpen who spoke to us on this matter. <br/><br />
<br/><br />
<br />
<b>A Sniffer-O-Meter could be made to smell these same 14 volatiles and to give a signal dependent on what combination of volatiles is detected.</b> The Snifferomyces is designed to be a general platform for any possible smell, smelling explosives is only one of the possible applications. The Sniffer-O-Meter could be redesigned to be carried around or to stay at a central position, like a fire detector. <br/><br />
<br/><br />
<b>"Micro-organisms and GMOs would definitely be used if it would improve the National Security." </b><br/><br />
The most important feature should be a very low number of false positives. It is a waste when the team responds to a false alarm, this costs a lot of time and money. Genetic modification is a new, important technology which, when whithin certain safety standards should definitely be used. At the moment we are experimenting with a chemical 'Nose', but this technology also responds to coca-cola, which has caused a lot of false alarms. In the lab a small error rate might be seen as acceptable, but in the field this is less so. <br/><br />
<br/><br />
On the job, dog and trainer work together as coworkers. And even though canine is trained to smell, his secundary role is to give a secure feeling to the crowd at an airport and the trainer. Of course this role would never be replaced by micro-organisms, although they could prove to become a solid addition to the general equipment. </p><br/><br />
<br/><br />
We would like to thank Rick van Vulpen for a nice chat on this subject! <br/><br />
The picture is from "Safety and Security", October 2012, a supplement of the Telegraaf.<br/><br />
<br />
<br/><h3>Talk with Dr. Lutter about the applicability of our research within the medical field </h3><br />
To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter ( is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. </br><br />
<br/>Has we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably eventually lead up to a new detection method in the medical field. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/><b>Intensive care </b><br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br><b>Resistant TB </b><br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/><b>HIV and TB</b> <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/><b>Fact:</b><i> From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB.</i> <br/> <a href="http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx">www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx</a> <br/><br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. <br/><br />
<br/>We would like to thank Dr. Rene Lutter for his input in our project! <br/> </div><br />
<br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-10-26T14:52:52Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<br />
<br />
<br />
<h2>Snifferomyces - A Tuberculosis Screening Automaton</h2><br><br />
<p> What is the use of technology, if it cannot contribute to improving human life? With this thought in mind, the TU Delft 2012 iGEM team, composed of students from the life sciences, bioinformatics, applied physics, aerospace, maritime, mechanical and chemical engineering disciplines decided to use the platform of synthetic biology, addressing a real challenge affecting millions of people .<br />
<br/><br />
Inspired by the sniffer rats trained to smell the presence of tuberculosis, the team decided to build an autonomous olfactory system to detect volatile compounds, by re-inventing man's oldest industrial microorganism, yeast, to provide for a non-invasive, rapid and cost-effective diagnosis system for tuberculosis. The reason why we have chosen for yeast, is that yeast is relative cheap to grow. Furthermore yeast has the ability to sense low amounts of concentration of specific compounds and can be storage for a long time.</p><br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>A cheap test that quickly gives an reliable result, that can be taken by a 4x4 car to the people.</p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Remote areas can be easily reached. <br />
</br><h6>Evaluating of test result</h6>Now we did the tests with GFP but if would use a visible output, it would be very easy to see a result. Which also mean that there are not many facilities needed.<br />
</br><h6>Cheap</h6>The producing of a large amount of yeast cells is in general not this expensive.<br />
</br><h6>Reliability</h6> This is something that should still be evaluated.<br />
</br><h6>Waiting time</h6> The waiting time for the result will be approximately 3 hours.</p><br />
<h3>Conclusion</h3> <br />
<p>We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<br />
<br><h2> Possible applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<h3> The Royal Dutch Military Police regarding a detector of explosives. </h3><br />
<br />
<p>Every day, 1800 member of the Royal Dutch Military Police are present at Schiphol to detect possible threats to the National Security. One part of their job is to be on the lookout for explosives. <b>This is where smell plays an important part! </b> Explosives are usually detected by Explo-dogs, dogs which have been trained to detect the scent associated with explosives. <br />
<br/><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/6/69/Explohond.jpg" width="600"/><br />
<br/><br />
<br />
An Explo-Dog is being trained to detect 14 different types of smells, which for security reasons will not be mentioned, in different combinations. The largest amount of explosives are covered by this intensive training after which they will work together with a canine trainer of the Military Police, such as Rick van Vulpen who spoke to us on this matter. <br/><br />
<br/><br />
<br />
<b>A Sniffer-O-Meter could be made to smell these same 14 volatiles and to give a signal dependent on what combination of volatiles is detected.</b> The Snifferomyces is designed to be a general platform for any possible smell, smelling explosives is only one of the possible applications. The Sniffer-O-Meter could be redesigned to be carried around or to stay at a central position, like a fire detector. <br/><br />
<br/><br />
<b>"Micro-organisms and GMOs would definitely be used if it would improve the National Security." </b><br/><br />
The most important feature should be a very low number of false positives. It is a waste when the team responds to a false alarm, this costs a lot of time and money. Genetic modification is a new, important technology which, when whithin certain safety standards should definitely be used. At the moment we are experimenting with a chemical 'Nose', but this technology also responds to coca-cola, which has caused a lot of false alarms. In the lab a small error rate might be seen as acceptable, but in the field this is less so. <br/><br />
<br/><br />
On the job, dog and trainer work together as coworkers. And even though canine is trained to smell, his secundary role is to give a secure feeling to the crowd at an airport and the trainer. Of course this role would never be replaced by micro-organisms, although they could prove to become a solid addition to the general equipment. </p><br/><br />
<br/><br />
We would like to thank Rick van Vulpen for a nice chat on this subject! <br/><br />
The picture is from "Safety and Security", October 2012, a supplement of the Telegraaf.<br/><br />
<br />
<br/><h3>Talk with Dr. Lutter about the applicability of our research within the medical field </h3><br />
To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter ( is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. </br><br />
<br/>Has we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably eventually lead up to a new detection method in the medical field. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/><b>Intensive care </b><br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br><b>Resistant TB </b><br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/><b>HIV and TB</b> <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/><b>Fact:</b><i> From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB.</i> <br/> <br/> [http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx] <br/><br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. <br/><br />
<br/>We would like to thank Dr. Rene Lutter for his input in our project! <br/> </div><br />
<br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-10-26T14:49:44Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br />
<br />
<br />
<h2>Snifferomyces - A Tuberculosis Screening Automaton</h2><br><br />
<p> What is the use of technology, if it cannot contribute to improving human life? With this thought in mind, the TU Delft 2012 iGEM team, composed of students from the life sciences, bioinformatics, applied physics, aerospace, maritime, mechanical and chemical engineering disciplines decided to use the platform of synthetic biology, addressing a real challenge affecting millions of people .<br />
<br/><br />
Inspired by the sniffer rats trained to smell the presence of tuberculosis, the team decided to build an autonomous olfactory system to detect volatile compounds, by re-inventing man's oldest industrial microorganism, yeast, to provide for a non-invasive, rapid and cost-effective diagnosis system for tuberculosis. The reason why we have chosen for yeast, is that yeast is relative cheap to grow. Furthermore yeast has the ability to sense low amounts of concentration of specific compounds and can be storage for a long time.</p><br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>A cheap test that quickly gives an reliable result, that can be taken by a 4x4 car to the people.</p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Remote areas can be easily reached. <br />
</br><h6>Evaluating of test result</h6>Now we did the tests with GFP but if would use a visible output, it would be very easy to see a result. Which also mean that there are not many facilities needed.<br />
</br><h6>Cheap</h6>The producing of a large amount of yeast cells is in general not this expensive.<br />
</br><h6>Reliability</h6> This is something that should still be evaluated.<br />
</br><h6>Waiting time</h6> The waiting time for the result will be approximately 3 hours.</p><br />
<h3>Conclusion</h3> <br />
<p>We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<br />
<br><h2> Possible applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<h3> The Royal Dutch Military Police regarding a detector of explosives. </h3><br />
<br />
<p>Every day, 1800 member of the Royal Dutch Military Police are present at Schiphol to detect possible threats to the National Security. One part of their job is to be on the lookout for explosives. <b>This is where smell plays an important part! </b> Explosives are usually detected by Explo-dogs, dogs which have been trained to detect the scent associated with explosives. <br />
<br/><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/6/69/Explohond.jpg" width="600"/><br />
<br/><br />
<br />
An Explo-Dog is being trained to detect 14 different types of smells, which for security reasons will not be mentioned, in different combinations. The largest amount of explosives are covered by this intensive training after which they will work together with a canine trainer of the Military Police, such as Rick van Vulpen who spoke to us on this matter. <br/><br />
<br/><br />
<br />
<b>A Sniffer-O-Meter could be made to smell these same 14 volatiles and to give a signal dependent on what combination of volatiles is detected.</b> The Snifferomyces is designed to be a general platform for any possible smell, smelling explosives is only one of the possible applications. The Sniffer-O-Meter could be redesigned to be carried around or to stay at a central position, like a fire detector. <br/><br />
<br/><br />
<b>"Micro-organisms and GMOs would definitely be used if it would improve the National Security." </b><br/><br />
The most important feature should be a very low number of false positives. It is a waste when the team responds to a false alarm, this costs a lot of time and money. Genetic modification is a new, important technology which, when whithin certain safety standards should definitely be used. At the moment we are experimenting with a chemical 'Nose', but this technology also responds to coca-cola, which has caused a lot of false alarms. In the lab a small error rate might be seen as acceptable, but in the field this is less so. <br/><br />
<br/><br />
On the job, dog and trainer work together as coworkers. And even though canine is trained to smell, his secundary role is to give a secure feeling to the crowd at an airport and the trainer. Of course this role would never be replaced by micro-organisms, although they could prove to become a solid addition to the general equipment. </p><br/><br />
<br/><br />
We would like to thank Rick van Vulpen for a nice chat on this subject! <br/><br />
The picture is from "Safety and Security", October 2012, a supplement of the Telegraaf.<br/><br />
<br />
<br/><h3>Talk with Dr. Lutter about the applicability of our research within the medical field </h3><br />
To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter ( is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. <br />
<br/>Has we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably eventually lead up to a new detection method in the medical field. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/><b>Intensive care </b><br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br><b>Resistant TB </b><br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/><b>HIV and TB</b> <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/><b>Fact:</b><i> From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB.</i> <br/> <br/> [http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx] <br/><br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. <br/><br />
<br/>We would like to thank Dr. Rene Lutter for his input in our project! <br/> </div><br />
<br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-10-26T14:48:13Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br />
<br />
<br />
<h2>Snifferomyces - A Tuberculosis Screening Automaton</h2><br><br />
<p> What is the use of technology, if it cannot contribute to improving human life? With this thought in mind, the TU Delft 2012 iGEM team, composed of students from the life sciences, bioinformatics, applied physics, aerospace, maritime, mechanical and chemical engineering disciplines decided to use the platform of synthetic biology, addressing a real challenge affecting millions of people .<br />
<br/><br />
Inspired by the sniffer rats trained to smell the presence of tuberculosis, the team decided to build an autonomous olfactory system to detect volatile compounds, by re-inventing man's oldest industrial microorganism, yeast, to provide for a non-invasive, rapid and cost-effective diagnosis system for tuberculosis. The reason why we have chosen for yeast, is that yeast is relative cheap to grow. Furthermore yeast has the ability to sense low amounts of concentration of specific compounds and can be storage for a long time.</p><br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>A cheap test that quickly gives an reliable result, that can be taken by a 4x4 car to the people.</p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Remote areas can be easily reached. <br />
</br><h6>Evaluating of test result</h6>Now we did the tests with GFP but if would use a visible output, it would be very easy to see a result. Which also mean that there are not many facilities needed.<br />
</br><h6>Cheap</h6>The producing of a large amount of yeast cells is in general not this expensive.<br />
</br><h6>Reliability</h6> This is something that should still be evaluated.<br />
</br><h6>Waiting time</h6> The waiting time for the result will be approximately 3 hours.</p><br />
<h3>Conclusion</h3> <br />
<p>We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<br />
<br><h2> Possible applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<h3> The Royal Dutch Military Police regarding a detector of explosives. </h3><br />
<br />
<p>Every day, 1800 member of the Royal Dutch Military Police are present at Schiphol to detect possible threats to the National Security. One part of their job is to be on the lookout for explosives. <b>This is where smell plays an important part! </b> Explosives are usually detected by Explo-dogs, dogs which have been trained to detect the scent associated with explosives. <br />
<br/><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/6/69/Explohond.jpg" width="600"/><br />
<br/><br />
<br />
An Explo-Dog is being trained to detect 14 different types of smells, which for security reasons will not be mentioned, in different combinations. The largest amount of explosives are covered by this intensive training after which they will work together with a canine trainer of the Military Police, such as Rick van Vulpen who spoke to us on this matter. <br/><br />
<br/><br />
<br />
<b>A Sniffer-O-Meter could be made to smell these same 14 volatiles and to give a signal dependent on what combination of volatiles is detected.</b> The Snifferomyces is designed to be a general platform for any possible smell, smelling explosives is only one of the possible applications. The Sniffer-O-Meter could be redesigned to be carried around or to stay at a central position, like a fire detector. <br/><br />
<br/><br />
<b>"Micro-organisms and GMOs would definitely be used if it would improve the National Security." </b><br/><br />
The most important feature should be a very low number of false positives. It is a waste when the team responds to a false alarm, this costs a lot of time and money. Genetic modification is a new, important technology which, when whithin certain safety standards should definitely be used. At the moment we are experimenting with a chemical 'Nose', but this technology also responds to coca-cola, which has caused a lot of false alarms. In the lab a small error rate might be seen as acceptable, but in the field this is less so. <br/><br />
<br/><br />
On the job, dog and trainer work together as coworkers. And even though canine is trained to smell, his secundary role is to give a secure feeling to the crowd at an airport and the trainer. Of course this role would never be replaced by micro-organisms, although they could prove to become a solid addition to the general equipment. </p><br/><br />
<br/><br />
We would like to thank Rick van Vulpen for a nice chat on this subject! <br/><br />
The picture is from "Safety and Security", October 2012, a supplement of the Telegraaf.<br />
<br />
<br/><h3>Talk with Dr. Lutter about the applicability of our research within the medical field </h3><br/><br />
<br/>To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter ( is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. <br/><br />
<br/>Has we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably eventually lead up to a new detection method in the medical field. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/><b>Intensive care </b><br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br><b>Resistant TB </b><br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/><b>HIV and TB</b> <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/><b>Fact:</b><i> From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB.</i> <br/> <br/> [http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx] <br/><br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. <br/><br />
<br/>We would like to thank Dr. Rene Lutter for his input in our project! <br/> </div><br />
<br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-10-26T14:45:56Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br />
<br />
<br />
<h2>Snifferomyces - A Tuberculosis Screening Automaton</h2><br><br />
<p> What is the use of technology, if it cannot contribute to improving human life? With this thought in mind, the TU Delft 2012 iGEM team, composed of students from the life sciences, bioinformatics, applied physics, aerospace, maritime, mechanical and chemical engineering disciplines decided to use the platform of synthetic biology, addressing a real challenge affecting millions of people .<br />
<br/><br />
Inspired by the sniffer rats trained to smell the presence of tuberculosis, the team decided to build an autonomous olfactory system to detect volatile compounds, by re-inventing man's oldest industrial microorganism, yeast, to provide for a non-invasive, rapid and cost-effective diagnosis system for tuberculosis. The reason why we have chosen for yeast, is that yeast is relative cheap to grow. Furthermore yeast has the ability to sense low amounts of concentration of specific compounds and can be storage for a long time.</p><br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>A cheap test that quickly gives an reliable result, that can be taken by a 4x4 car to the people.</p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Remote areas can be easily reached. <br />
</br><h6>Evaluating of test result</h6>Now we did the tests with GFP but if would use a visible output, it would be very easy to see a result. Which also mean that there are not many facilities needed.<br />
</br><h6>Cheap</h6>The producing of a large amount of yeast cells is in general not this expensive.<br />
</br><h6>Reliability</h6> This is something that should still be evaluated.<br />
</br><h6>Waiting time</h6> The waiting time for the result will be approximately 3 hours.</p><br />
<h3>Conclusion</h3> <br />
<p>We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<br />
<br><h2> Possible applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<h3> The Royal Dutch Military Police regarding a detector of explosives. </h3><br />
<br />
<p>Every day, 1800 member of the Royal Dutch Military Police are present at Schiphol to detect possible threats to the National Security. One part of their job is to be on the lookout for explosives. <b>This is where smell plays an important part! </b> Explosives are usually detected by Explo-dogs, dogs which have been trained to detect the scent associated with explosives. <br />
<br/><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/6/69/Explohond.jpg" width="600"/><br />
<br/><br />
<br />
An Explo-Dog is being trained to detect 14 different types of smells, which for security reasons will not be mentioned, in different combinations. The largest amount of explosives are covered by this intensive training after which they will work together with a canine trainer of the Military Police, such as Rick van Vulpen who spoke to us on this matter. <br/><br />
<br/><br />
<br />
<b>A Sniffer-O-Meter could be made to smell these same 14 volatiles and to give a signal dependent on what combination of volatiles is detected.</b> The Snifferomyces is designed to be a general platform for any possible smell, smelling explosives is only one of the possible applications. The Sniffer-O-Meter could be redesigned to be carried around or to stay at a central position, like a fire detector. <br/><br />
<br/><br />
<b>"Micro-organisms and GMOs would definitely be used if it would improve the National Security." </b><br/><br />
The most important feature should be a very low number of false positives. It is a waste when the team responds to a false alarm, this costs a lot of time and money. Genetic modification is a new, important technology which, when whithin certain safety standards should definitely be used. At the moment we are experimenting with a chemical 'Nose', but this technology also responds to coca-cola, which has caused a lot of false alarms. In the lab a small error rate might be seen as acceptable, but in the field this is less so. <br/><br />
<br/><br />
On the job, dog and trainer work together as coworkers. And even though canine is trained to smell, his secundary role is to give a secure feeling to the crowd at an airport and the trainer. Of course this role would never be replaced by micro-organisms, although they could prove to become a solid addition to the general equipment. </p><br/><br />
<br/><br />
We would like to thank Rick van Vulpen for a nice chat on this subject! <br/><br />
The picture is from "Safety and Security", October 2012, a supplement of the Telegraaf.<br />
<br />
<br/><h2>Talk with Dr. Lutter - applicability within the medical field </h2><br/><br />
<br/>To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter ( is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. <br/><br />
<br/>Has we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably eventually lead up to a new detection method in the medical field. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/><b>Intensive care </b><br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br><b>Resistant TB </b><br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/><b>HIV and TB</b> <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/><b>Fact:</b><i> From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB.</i> <br/> <br/> [http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx] <br/><br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. <br/><br />
<br/>We would like to thank Dr. Rene Lutter for his input in our project! <br/> </div><br />
<br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-10-26T14:37:41Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br />
<br />
<br />
<h2>Snifferomyces - A Tuberculosis Screening Automaton</h2><br><br />
<p> What is the use of technology, if it cannot contribute to improving human life? With this thought in mind, the TU Delft 2012 iGEM team, composed of students from the life sciences, bioinformatics, applied physics, aerospace, maritime, mechanical and chemical engineering disciplines decided to use the platform of synthetic biology, addressing a real challenge affecting millions of people .<br />
<br/><br />
Inspired by the sniffer rats trained to smell the presence of tuberculosis, the team decided to build an autonomous olfactory system to detect volatile compounds, by re-inventing man's oldest industrial microorganism, yeast, to provide for a non-invasive, rapid and cost-effective diagnosis system for tuberculosis. The reason why we have chosen for yeast, is that yeast is relative cheap to grow. Furthermore yeast has the ability to sense low amounts of concentration of specific compounds and can be storage for a long time.</p><br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>A cheap test that quickly gives an reliable result, that can be taken by a 4x4 car to the people.</p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Remote areas can be easily reached. <br />
</br><h6>Evaluating of test result</h6>Now we did the tests with GFP but if would use a visible output, it would be very easy to see a result. Which also mean that there are not many facilities needed.<br />
</br><h6>Cheap</h6>The producing of a large amount of yeast cells is in general not this expensive.<br />
</br><h6>Reliability</h6> This is something that should still be evaluated.<br />
</br><h6>Waiting time</h6> The waiting time for the result will be approximately 3 hours.</p><br />
<h3>Conclusion</h3> <br />
<p>We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<br />
<br><h2> Possible applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<h3> The Royal Dutch Military Police regarding a detector of explosives. </h3><br />
<br />
<p>Every day, 1800 member of the Royal Dutch Military Police are present at Schiphol to detect possible threats to the National Security. One part of their job is to be on the lookout for explosives. <b>This is where smell plays an important part! </b> Explosives are usually detected by Explo-dogs, dogs which have been trained to detect the scent associated with explosives. <br />
<br/><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/6/69/Explohond.jpg" width="600"/><br />
<br/><br />
<br />
An Explo-Dog is being trained to detect 14 different types of smells, which for security reasons will not be mentioned, in different combinations. The largest amount of explosives are covered by this intensive training after which they will work together with a canine trainer of the Military Police, such as Rick van Vulpen who spoke to us on this matter. <br/><br />
<br/><br />
<br />
<b>A Sniffer-O-Meter could be made to smell these same 14 volatiles and to give a signal dependent on what combination of volatiles is detected.</b> The Snifferomyces is designed to be a general platform for any possible smell, smelling explosives is only one of the possible applications. The Sniffer-O-Meter could be redesigned to be carried around or to stay at a central position, like a fire detector. <br/><br />
<br/><br />
<b>"Micro-organisms and GMOs would definitely be used if it would improve the National Security." </b><br/><br />
The most important feature should be a very low number of false positives. It is a waste when the team responds to a false alarm, this costs a lot of time and money. Genetic modification is a new, important technology which, when whithin certain safety standards should definitely be used. At the moment we are experimenting with a chemical 'Nose', but this technology also responds to coca-cola, which has caused a lot of false alarms. In the lab a small error rate might be seen as acceptable, but in the field this is less so. <br/><br />
<br/><br />
On the job, dog and trainer work together as coworkers. And even though canine is trained to smell, his secundary role is to give a secure feeling to the crowd at an airport and the trainer. Of course this role would never be replaced by micro-organisms, although they could prove to become a solid addition to the general equipment. </p><br/><br />
<br/><br />
We would like to thank Rick van Vulpen for a nice chat on this subject! <br/><br />
The picture is from "Safety and Security", October 2012, a supplement of the Telegraaf.<br />
<br />
<br/><h2>Talk with Dr. Lutter about the applicability of our research within the medical field </h2><br/><br />
<br/>To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter ( is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. <br/><br />
<br/>Has we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably eventually lead up to a new detection method in the medical field. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/>Intensive care <br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br/>Resistant TB <br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/>HIV and TB <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/>Fact: From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB. <br/> <br/> [http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx] <br/><br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. <br/><br />
<br/>We would like to thank Dr. Rene Lutter for his input in our project! <br/> </div><br />
<br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-10-26T14:36:20Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
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<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br />
<br />
<br />
<h2>Snifferomyces - A Tuberculosis Screening Automaton</h2><br><br />
<p> What is the use of technology, if it cannot contribute to improving human life? With this thought in mind, the TU Delft 2012 iGEM team, composed of students from the life sciences, bioinformatics, applied physics, aerospace, maritime, mechanical and chemical engineering disciplines decided to use the platform of synthetic biology, addressing a real challenge affecting millions of people .<br />
<br/><br />
Inspired by the sniffer rats trained to smell the presence of tuberculosis, the team decided to build an autonomous olfactory system to detect volatile compounds, by re-inventing man's oldest industrial microorganism, yeast, to provide for a non-invasive, rapid and cost-effective diagnosis system for tuberculosis. The reason why we have chosen for yeast, is that yeast is relative cheap to grow. Furthermore yeast has the ability to sense low amounts of concentration of specific compounds and can be storage for a long time.</p><br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>A cheap test that quickly gives an reliable result, that can be taken by a 4x4 car to the people.</p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Remote areas can be easily reached. <br />
</br><h6>Evaluating of test result</h6>Now we did the tests with GFP but if would use a visible output, it would be very easy to see a result. Which also mean that there are not many facilities needed.<br />
</br><h6>Cheap</h6>The producing of a large amount of yeast cells is in general not this expensive.<br />
</br><h6>Reliability</h6> This is something that should still be evaluated.<br />
</br><h6>Waiting time</h6> The waiting time for the result will be approximately 3 hours.</p><br />
<h3>Conclusion</h3> <br />
<p>We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<br />
<br><h2> Possible applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<h3> The Royal Dutch Military Police regarding a detector of explosives. </h3><br />
<br />
<p>Every day, 1800 member of the Royal Dutch Military Police are present at Schiphol to detect possible threats to the National Security. One part of their job is to be on the lookout for explosives. <b>This is where smell plays an important part! </b> Explosives are usually detected by Explo-dogs, dogs which have been trained to detect the scent associated with explosives. <br />
<br/><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/6/69/Explohond.jpg" width="600"/><br />
<br/><br />
<br />
An Explo-Dog is being trained to detect 14 different types of smells, which for security reasons will not be mentioned, in different combinations. The largest amount of explosives are covered by this intensive training after which they will work together with a canine trainer of the Military Police, such as Rick van Vulpen who spoke to us on this matter. <br/><br />
<br/><br />
<br />
<b>A Sniffer-O-Meter could be made to smell these same 14 volatiles and to give a signal dependent on what combination of volatiles is detected.</b> The Snifferomyces is designed to be a general platform for any possible smell, smelling explosives is only one of the possible applications. The Sniffer-O-Meter could be redesigned to be carried around or to stay at a central position, like a fire detector. <br/><br />
<br/><br />
<b>"Micro-organisms and GMOs would definitely be used if it would improve the National Security." </b><br/><br />
The most important feature should be a very low number of false positives. It is a waste when the team responds to a false alarm, this costs a lot of time and money. Genetic modification is a new, important technology which, when whithin certain safety standards should definitely be used. At the moment we are experimenting with a chemical 'Nose', but this technology also responds to coca-cola, which has caused a lot of false alarms. In the lab a small error rate might be seen as acceptable, but in the field this is less so. <br/><br />
<br/><br />
On the job, dog and trainer work together as coworkers. And even though canine is trained to smell, his secundary role is to give a secure feeling to the crowd at an airport and the trainer. Of course this role would never be replaced by micro-organisms, although they could prove to become a solid addition to the general equipment. </p><br/><br />
<br/><br />
We would like to thank Rick van Vulpen for a nice chat on this subject! <br/><br />
The picture is from "Safety and Security", October 2012, a supplement of the Telegraaf.</div><br />
<br />
<br/><h2>Talk with Dr. Lutter about the applicability of our research within the medical field </h2><br/><br />
<br/>To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter ( is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. <br/><br />
<br/>Has we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably eventually lead up to a new detection method in the medical field. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/>Intensive care <br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br/>Resistant TB <br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/>HIV and TB <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/>Fact: From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB. <br/> <br/> [http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx] <br/><br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. <br/><br />
<br/>We would like to thank Dr. Rene Lutter for his input in our project! <br/><br />
<br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-10-26T14:35:11Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/e/ed/Nieuwe_header_human_practices.jpg" align="middle" width="100%"><br />
<br />
<br />
<br />
<h2>Snifferomyces - A Tuberculosis Screening Automaton</h2><br><br />
<p> What is the use of technology, if it cannot contribute to improving human life? With this thought in mind, the TU Delft 2012 iGEM team, composed of students from the life sciences, bioinformatics, applied physics, aerospace, maritime, mechanical and chemical engineering disciplines decided to use the platform of synthetic biology, addressing a real challenge affecting millions of people .<br />
<br/><br />
Inspired by the sniffer rats trained to smell the presence of tuberculosis, the team decided to build an autonomous olfactory system to detect volatile compounds, by re-inventing man's oldest industrial microorganism, yeast, to provide for a non-invasive, rapid and cost-effective diagnosis system for tuberculosis. The reason why we have chosen for yeast, is that yeast is relative cheap to grow. Furthermore yeast has the ability to sense low amounts of concentration of specific compounds and can be storage for a long time.</p><br />
<br />
<p>For our Human Practice we did a study in to what extent our proof of principle, if it would be translated into a product, could make a difference. To answer this we evaluate the most important parts of this question below. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/> TB becomes even a larger problem because of HIV, 60.1% of TB patients tested for HIV were HIV-positive. HIV-patients with TB have to be cured even faster because of their immune system is weakened.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
<div style="position:relative; align:center; top:0; left:0; width:580px; height:240px; border:0; margin:0 0 20px 0; padding:0; "><br />
<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
<img src="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" name="kugroup" width="570" border="0" id="kugroup" /></a></div> <br />
<br/><br/><br/><br/><br/><br/><br/> <br />
<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or are not very reliable, all these reasons are posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and also suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
<body><br />
<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
</body><br />
<br />
<h3>Our ideal Solution</h3><br />
<p>A cheap test that quickly gives an reliable result, that can be taken by a 4x4 car to the people.</p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Remote areas can be easily reached. <br />
</br><h6>Evaluating of test result</h6>Now we did the tests with GFP but if would use a visible output, it would be very easy to see a result. Which also mean that there are not many facilities needed.<br />
</br><h6>Cheap</h6>The producing of a large amount of yeast cells is in general not this expensive.<br />
</br><h6>Reliability</h6> This is something that should still be evaluated.<br />
</br><h6>Waiting time</h6> The waiting time for the result will be approximately 3 hours.</p><br />
<h3>Conclusion</h3> <br />
<p>We strongly believe that our project is well worth to be further developed. We believe it can make a change in how diagnostics in remote areas take place. But also for areas with facilities, it can be a cheap alternative for the diagnosing of other diseases that can be detected by specific compounds.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011 according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO.</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in july 2011. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. This picture of the Hospital is taken in july 2011. In contrary to what Wikipedia states, part of this building is still being used as a hospital.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
<br/><br />
<br />
<br />
<br><h2> Possible applications of the Sniffer-O-Meter!</h2> </br><br />
<br />
<h3> The Royal Dutch Military Police regarding a detector of explosives. </h3><br />
<br />
<p>Every day, 1800 member of the Royal Dutch Military Police are present at Schiphol to detect possible threats to the National Security. One part of their job is to be on the lookout for explosives. <b>This is where smell plays an important part! </b> Explosives are usually detected by Explo-dogs, dogs which have been trained to detect the scent associated with explosives. <br />
<br/><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/6/69/Explohond.jpg" width="600"/><br />
<br/><br />
<br />
An Explo-Dog is being trained to detect 14 different types of smells, which for security reasons will not be mentioned, in different combinations. The largest amount of explosives are covered by this intensive training after which they will work together with a canine trainer of the Military Police, such as Rick van Vulpen who spoke to us on this matter. <br/><br />
<br/><br />
<br />
<b>A Sniffer-O-Meter could be made to smell these same 14 volatiles and to give a signal dependent on what combination of volatiles is detected.</b> The Snifferomyces is designed to be a general platform for any possible smell, smelling explosives is only one of the possible applications. The Sniffer-O-Meter could be redesigned to be carried around or to stay at a central position, like a fire detector. <br/><br />
<br/><br />
<b>"Micro-organisms and GMOs would definitely be used if it would improve the National Security." </b><br/><br />
The most important feature should be a very low number of false positives. It is a waste when the team responds to a false alarm, this costs a lot of time and money. Genetic modification is a new, important technology which, when whithin certain safety standards should definitely be used. At the moment we are experimenting with a chemical 'Nose', but this technology also responds to coca-cola, which has caused a lot of false alarms. In the lab a small error rate might be seen as acceptable, but in the field this is less so. <br/><br />
<br/><br />
On the job, dog and trainer work together as coworkers. And even though canine is trained to smell, his secundary role is to give a secure feeling to the crowd at an airport and the trainer. Of course this role would never be replaced by micro-organisms, although they could prove to become a solid addition to the general equipment. </p><br/><br />
<br/><br />
We would like to thank Rick van Vulpen for a nice chat on this subject! <br/><br />
The picture is from "Safety and Security", October 2012, a supplement of the Telegraaf.</div><br />
<br />
<br/><h2>Talk with Dr. Lutter about the applicability of our research within the medical field <h2><br/><br />
<br/>To get a better overview of what the medical field would think of our research, we talk to Dr. Rene Lutter ( is doing research at the functioning of granuloma in tuberculosis and if you can read the functioning of granuloma from the parameters in breath-condensate, at the Academic Medical Center (AMC), University of Amsterdam, the Netherlands. <br/><br />
<br/>Has we explained our project to this doctor he became very enthusiastic about the many possibilities one can do with it. Of course plenty more research is needed before one can actually use this in the medical field, but the beginning of our project will probably eventually lead up to a new detection method in the medical field. He gave a couple of examples that would be improved with this new detection method, those are listed below. <br/><br />
<br/>Intensive care <br/><br />
<br/>There are people coming to the intensive care with an unknown infection which can be deadly if not treated on time. Now a days doctors first need a sample of the infection, let the bacteria grow and identify it, and treat the patient with the right medicine. This whole process cost a lot of time, which some patients do not have unfortunately. If we would have a broad platform of detection many different gaseous compounds, the diagnosing of the unknown infections would be a lot faster and more people would cured. <br/><br />
<br/>Resistant TB <br/><br />
<br/>There are several types of resistant TB, which means that the medicine will not cure the TB from the patient. A patient gets resistant TB either from taking their medication wrong or directly from another resistant TB patient. Diagnosing if a patient has resistant TB takes approximately 2 to 3 months. With the upcoming technology one would be able to detect different compounds of a resistant TB, and one would find out quickly if someone is suffering from a resistant TB and would get the appropriate treatment faster. <br/><br />
<br/>HIV and TB <br/><br />
<br/>People who are infected with HIV have a disoriented immune system. This will give the opportunity for other infections to easily enter the human body. TB bacteria become active if the immune system cannot stop this from growing. So the combination of those two diseases is in many cases deadly if not diagnosed and treated. <br/><br />
<br/>Fact: From the 8.8 million people who got TB in 2010, there were 1.1 million also HIV-positive.82% of those people live in the Sub-Saharan Africa. From all the aids patients who die, half of them die from TB. <br/> <br/> [http://www.artsenzondergrenzen.nl/over-ons/dossiers/medische-dossiers/dossier-tuberculose/tuberculose-en-hiv-aids.aspx] <br/><br />
<br/>Diagnosing TB by patients with saliva-test or even by x-ray photos who are seropositive is not always giving the correct diagnosis. So in order to treat these patients a better and faster diagnose of TB is necessary. So by able to detect compounds of TB, no matter the patient’s own condition, a proper diagnose can be made and more people would be treated in much earlier state. <br/><br />
<br/>To conclude, our research has many possibilities within the medical field. So hopefully in the near future this wills safe many people. <br/><br />
<br/>We would like to thank Dr. Rene Lutter for his input in our project! <br/><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/EthicsTeam:TU-Delft/Ethics2012-09-27T00:45:39Z<p>Stephanielubbers: </p>
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<p>Together with the Rathenau Institute, our team will organize one of the two debate rounds at the event Meeting of Young Minds. This debate will take place the Friday of the Jamboree, October 5th. The topic of this debate will be about the release of research details on the creation of highly transmissible H5N1 (bird flu) in the lab. With different experts we will discuss different statements like:<br />
<br/><br />
<br/><br />
• The NSABB made the right choice to give permission for publication of this research<br />
<br/><br />
• Looking at the potential risks, this research should not have started in the first place (accidents in the past, e.g. 1977 pandemic of H1N1, which probably escaped from the lab)<br />
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• The scientific community has to remain ‘open access’ – restricting access to scientific literature hampers the progress in science. <br />
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During this debate the public will get also a chance to express their opinion. So please come and be part of this interesting debate!<br />
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<h3>Ethical considerations during scientific investigation</h3> </td></tr><br />
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Our team had extra help from an embedded humanist, named Daan Schuurbiers, who followed the research as a midstream modulation project. Including Daan to the project, the team became also aware of the social sciences of the research. ‘’Midstream modulation asks how research is to be carried out, which is the main business of research, rather than whether a research project should be carried out, which is an upstream policy question. It is a means to evaluate and adjust research decisions in light of societal factors while the research process is taking place.’’ There are 3 different stages in the governance of science and technology, upstream, downstream and midstream modulation, see figure on the right. So by thinking about midstream modulation, this project is connected with the scientific research as well as to the social issues. In this documentary you will see how science will meet the human interest in many ways. <br />
<br/><br />
<h6>D. Schuurbiers, E. Fisher (2009), Lab-scale intervention. Science & Society Series on Convergence Research, EMBO reports VOL 10 NO 5</h6></p></td><br />
<td><a href="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" target="_blank"><img src="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" width="140" height="180" align="right" valign="bottom" /></a></td><br />
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<p><br />
Daan Schuurbiers is director of the Pilot Plant (De Proeffabriek), consultancy for responsible innovation. Daan studied chemistry and philosophy at the University of Amsterdam and has a PhD in ethics of technology from Delft University of Technology. His work centers on the social and ethical dimensions of newly emerging science and technologies. Daan's research efforts have focused on the design of new forms of dialogue between social and natural scientists, enhancing socio-ethical reflection in early stages of research. In addition to teaching and research, Daan has extensive experience in project management and consultancy, particularly in the area of dialogue and engagement with science and technology. <br />
He has published in academic journals as well as the popular press and has been involved in the organization of a range of teaching courses, master classes, competitions, workshops and other events throughout Europe. He now combines his writing, teaching, research and management skills in his work for the Pilot Plant, advising on ways to encourage reflection in research and to strengthen stakeholder engagement.<br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-09-27T00:43:48Z<p>Stephanielubbers: </p>
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<h2>Snifferomyces - A Tuberculosis Screening Automaton</h2><br><br />
<p> What is the use of technology, if it cannot contribute to improving human life? With this thought in mind, the TU Delft 2012 iGEM team, composed of students from the life sciences, bioinformatics, applied physics, aerospace, maritime, mechanical and chemical engineering disciplines decided to use the platform of synthetic biology, addressing a real challenge affecting millions of people .<br />
<br/><br />
Inspired by the sniffer rats trained to smell the presence of tuberculosis, the team decided to build an autonomous olfactory system to detect volatile compounds, by re-inventing man's oldest industrial microorganism, yeast, to provide for a non-invasive, rapid and cost-effective diagnosis system for tuberculosis. The reason why we have chosen for yeast, is that yeast is relative cheap to grow. Furthermore yeast has the ability to sense low amounts of concentration of specific compounds and can be storage for a long time.</p><br />
<br />
<p>For our Human Practice we did a study to in what extent our proof of principle, if it would be translated into a product, could make a difference. Below we evaluate the most important questions. </p><br />
<h3>What is Tuberculosis?</h3><br />
<p>Tuberculosis is a bacterial infection. TB usually attacks the lungs, but can also attack other parts of the body, such as the brain, spine, or kidneys. TB bacteria can live in the body without making a person sick. This is called latent TB infection. People with latent TB infection do not feel sick, do not have TB symptoms, and cannot spread TB bacteria to others. Some people with latent TB infection go on to develop TB disease.<br />
<br/>In 2010, 8.8 million people were infected with TB and 1.4 million died from it. Over 95% of TB deaths occur in low -and middle- income countries.</p><br />
<p>At the map below you can see the countries suffering from Tuberculosis. According to <a href="http://www.vaccinatiesopreis.nl">www.vaccinatiesopreis.nl</a> the dark green refers to many cases of TB, the light green to less and the white to a few cases.</p><br />
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<a href="https://static.igem.org/mediawiki/igem.org/4/4a/TBmap.gif" rel="lightbox" title="Tuberculosismap"><br />
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<br />
<h3>The problem</h3><br />
<p>The problem of tuberculosis lies mainly in the less developed countries. The frontline are the remote areas where the people have no or limited access to hospitals with sufficient facilities. Standard TB diagnostic tools are either expensive and need to be used in a lab setting or not very reliable, posing major barriers for diagnosing.<br />
</p><br />
<br />
<h3>Six Ways to Diagnose Tuberculosis</h3><br />
<p>These are six main diagnosis tools for TB. The problem is that there is not one of them that is very reliable and suitable for the frontline. Not suitable for the frontline because it needs facilities, doesn't give a quick result and/or is expensive.</p><br />
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<ul><br />
<li>Tuberculin Skin Test (TST)<br />
<li>Sputum Smear Microscopy (SSM)<br />
<li>Polymerase Chain Reaction (PCR)<br />
<li>Blood Test for TB detection<br />
<li>Chest X-ray<br />
<li>Culture<br />
</ul><br />
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<h3>Our ideal Solution</h3><br />
<p>A cheap test that quickly gives an reliable result, that can be taken by a 4x4 car to the people.</p><br />
<br />
<h3>What would a test based on our principle contribute?</h3><br />
<p><h6>Reach</h6>Yeast cells can be kept in dried form, which makes them very well transportable and easy to store. Remote areas can be easily reached. <br />
</br><h6>Evaluating of test result</h6>Now we did the tests with GFP but if would use a visible output, it would be very easy to see a result. Which also mean that there are not many facilities needed.<br />
</br><h6>Cheap</h6>The producing of a large amount of yeast cells is in general not this expensive.<br />
</br><h6>Reliability</h6> This is something that should still be evaluated.<br />
</br><h6>Waiting time</h6> The waiting time for the result will be approximately 3 hours.</p><br />
<br/><br />
<br />
<h3>Example Mozambique; lack of facilities</h3><br />
Mozambique ranks the 19th among the 22 Tuberculosis High Burden Countries 2011.<br />
First some facts and figures about Mozambique according to the <a href="http://www.afro.who.int/en/mozambique/country-programmes/aids-tuberculosis-and-malaria/tuberculosis.html" target="_blank">WHO</a><br />
<p>One of our team members, Isabelle, traveled to Mozambique in 2011, accompanied by a lung physician. The lack of the diagnostic capacity is very clear at the hospital of Ilha de Mocambique. Ilha de Mocambique inhabits 14.000 people and they are relying on the hospital there. The picture of the Hospital is taken in july 2011.</p><img src="https://static.igem.org/mediawiki/igem.org/b/b2/HospitalILHAM.JPG" height="330" width="600"/><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/brainstormingTeam:TU-Delft/brainstorming2012-09-25T21:04:45Z<p>Stephanielubbers: </p>
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<p>The first weeks of our project (Week 12 - Week 19) we spent a lot of time in brainstorming sessions. Before ending to our final project theme, we came up with many meetings where all the team and the instructors were present. Each meeting had each special purpose; each of us had to study previous iGEM projects, articles and any other available source of information in order to come up with ideas about potential iGEM topics.</p><br />
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<p>For these choices also helped the crash course we had in collaboration with the <a href=” https://2012.igem.org/Team:Amsterdam“ target=”_blank”>Amsterdam 2012 iGEM team</a> Those topics had to be enhanced with structured arguments, always keeping in mind whether they could stand as iGEM project. Additionally, they were criticised by all members trying to focus on some directions and excluding others. Those meetings helped us a lot in understanding what iGEM stands for, what we want to succeed and how we could satisfy our wills as a team with students with different knowledge background. We not only learned how to argue about our choices, but also how to collaborate with each other and become an enduringly more tight team. By the 15th Week we came up with final 9 topics; those were: </p><br />
<dl><br />
<dd>9. Frasme shifting</dd><br />
<dd> 8. Smelling bacteria </dd><br />
<dd> 7. Bioprinting </dd><br />
<dd> 6. Bee colony</dd><br />
<dd> 5. Bactocamera</dd><br />
<dd> 4. Biosphere</dd><br />
<dd> 3. Bio-solar panel</dd><br />
<dd> 2. Min E. coli</dd><br />
<dd> 1. Immune E.coli</dd><br />
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<p>And later, the 17th Week there was a presentation debate of the final 2 topics: Smelling Yeast and Antibeast. <br />
Their advice to this gave: Han de Winde, Juan Keymer, Bertus Beaumont, Chirlmin Joo, Daniel Solis Escalante, Niels Kuijpers, Fabai Wu, Yaron Caspi and others. </p><br />
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<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/></body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-09-25T21:02:24Z<p>Stephanielubbers: </p>
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<h2>Human practice</h2><br />
<p>Our team focused on several part of the category called human practise. We were in a very good<br />
collaboration with a MSc student in Educational studies named Amalia Ephrat. During the brainstorm<br />
sessions the team helped her to observe collaborative learning activities.<br />
<br/><br />
<br/><br />
We are also part of a documentary called Lab-Life, which is filmed by Frank Theys. In this<br />
documentary he follows the daily life of the scientific research project of our team. For this<br />
documentary an embedded humanist, Daan Schuurbiers was partly involved with our p roject. His<br />
professional view on social sciences helped our team a lot.<br />
<br/><br />
<br/><br />
Furthermore, during the European jamboree TUDelft 2012 iGEM team will organize together with the Rathenau<br />
Institute a debate called Meeting of Young Minds. The subject of this debate will be the H5N1 virus<br />
and weather the research manuscript should have been published. This will be a very interesting<br />
debate with different experts, the team and of course the audience!<br />
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<p>During the brainstorm sessions a MSc student in Educational studies, Amalia Ephrat had recorded the way this team came to their final topic Snifferomyces! The team helped her to study the collaborative learning activities between students with different international backgrounds within the learning context of the University</p><br />
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<td colspan="2" align="left"><br/><h3>Who is Amalia Ephrat? – Our MSc students in Educational studies</h3><br />
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<p>Amalia Ephrat is a MSc student in Educational studies at Leiden, she<br />
did a short internship focused on collaborative learning<br />
activities between students with an international background within<br />
the learning context of the university.<br />
<br/><br />
<br/><br />
When students of diverse backgrounds participate in a project where<br />
collaborative learning is important, the individual differences can<br />
pose a series of challenges to the group processes. This is a well-<br />
known challenge for many Dutch universities, which makes it a relevant<br />
topic for educational research to investigate the means for<br />
intervention and the effects of those interventions on collaborative<br />
learning processes and outcomes.<br />
<br/><br />
<br/><br />
Her plan is to improve collaborative learning amongst students of<br />
different backgrounds, by designing research and conduct measurement<br />
during the brainstorming phase of the project. Research shall consist<br />
of qualitative exploratory methods using observational methods and<br />
interviews and quantitative research using several questionnaires,<br />
including collaborative skills, empathy and intercultural conflict<br />
management.<br />
<br/><br />
<br/><br />
The main focus of her research is the collaborative process in the<br />
iGEM group and the efficacy of the interventions of the supervisors to<br />
support the collaborative process in a culturally diverse group of<br />
students.<br />
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<p>The TU Delft 2012 team will be on seen on Belgian, Dutch and German television next year! During this project a Flemish documentary film director, Frank Theys was filming the team for his documentary Lab-Life. This full-length documentary is focused on how modern scientific research is being carried out, from the idea-conception through research, to results and publication. This documentary will become a real international scope on research, including multicultural aspects.<br />
<br/><br />
<br/><br />
Frank Theys started to record our team from the very beginning. The film director recorded many brainstorm sessions, and followed us till the final topic, Snifferomyces! Knowing what this project will be about, he started to film the amazing lab team while preforming experiments, but also the modellers who explain the importance of their contribution in the scientific world. And will film the final presentation at the Jamboree. Furthermore another interesting part of this documentary will be the focus on societal implications. The problems what comes with scientific research and the solutions and breakthroughs will be shown to a very brought audience on the television senders NOS, VRT and ZDF next year. <br />
<br/><br />
<br/><br />
By participating in this documentary our team will let a broad audience know about the daily life in the laboratory in the fields of the new technologies (NBIC). The team will inform people about what scientific research is about today. This means more than just doing lab work. Also other daily aspects that are connected to the research were filmed by Frank, like funding, public relations, social events, the team’s expectations of the research and possible applications, basically the whole biotope around a modern research team.<br />
<br/><br/><br />
We are the first iGEM team that a documentary has been done for it. Thus, the film may constitute a useful material for the following iGEM teams!!!!<br />
</p><br />
</td><br />
</tr><br />
<tr><br />
</td><br />
</tr><br />
<tr><br />
<td><br />
<p><br />
Our team had extra help from an embedded humanist, named Daan Schuurbiers, who followed the research as a midstream modulation project. Including Daan to the project, the team became also aware of the social sciences of the research. ‘’Midstream modulation asks how research is to be carried out, which is the main business of research, rather than whether a research project should be carried out, which is an upstream policy question. It is a means to evaluate and adjust research decisions in light of societal factors while the research process is taking place.’’ There are 3 different stages in the governance of science and technology, upstream, downstream and midstream modulation, see figure on the right. So by thinking about midstream modulation, this project is connected with the scientific research as well as to the social issues. In this documentary you will see how science will meet the human interest in many ways. <br />
<br/><br />
<h6>D. Schuurbiers, E. Fisher (2009), Lab-scale intervention. Science & Society Series on Convergence Research, EMBO reports VOL 10 NO 5</h6><br />
<br />
<td><img src="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" width="140" height="180" align="right" valign="bottom" /></td><br />
</tr><br />
<td colspan="2" align="left"><h3><br/>Who is Frank Theys? – Our film director</h3><br />
</td><br />
</tr><br />
<tr><br />
<td><br />
<p><br />
Frank Theys is a film and theatre director and visual artist. His work has been shown worldwide and belongs to the collections of a.o. the Museum of Modern Art (New York) and the Centre National de la Cinématographie (Paris). He received several international awards and the honourable title of Cultural Ambassador of Flanders. Currently he works on a documentary film called 'Lab-Life' in which he follows the daily life around a few scientific research projects. One of these projects is the iGEM team of TUDelft that he considers as an ideal project to introduce the world of science to a broad audience. <br />
Frank Theys has an MD in Philosophy and is currently doing a PhD in the Arts at the KULeuven. He teaches media art at the St-Lucas Art Academy in Ghent and art philosophy at the ArtScience Interfaculty at the Royal Art Academy in Den Hague. <br />
</p><br />
</td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/2/2b/Frank.png" width="140" height="180" align="right" valign="bottom" /></td><br />
</tr><br />
<center><br />
</table><br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/c/c0/Frank01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/c/c0/Frank01.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/b/b2/Frank02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/b/b2/Frank02.jpg' height=85 width=100 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/e/eb/Frank03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/e/eb/Frank03.jpg' height=85 width=100 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/3/38/Frank04.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/3/38/Frank04.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/9/91/Frank05.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/9/91/Frank05.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/3/3b/Frank06.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/3/3b/Frank06.jpg' height=90 width=98 /></a></td><br />
</tr><br />
</table><br />
</center><br />
<br/><br />
<table width="100%" ><br />
<tr><br />
<td colspan="2" align="left"><h3><br/>Who is Daan Schuurbiers? – Our embedded humanist</h3><br />
<br />
<tr><br />
<br />
<td><br />
<p><br />
Daan Schuurbiers is director of the Pilot Plant (De Proeffabriek), consultancy for responsible innovation. Daan studied chemistry and philosophy at the University of Amsterdam and has a PhD in ethics of technology from Delft University of Technology. His work centers on the social and ethical dimensions of newly emerging science and technologies. Daan's research efforts have focused on the design of new forms of dialogue between social and natural scientists, enhancing socio-ethical reflection in early stages of research. In addition to teaching and research, Daan has extensive experience in project management and consultancy, particularly in the area of dialogue and engagement with science and technology. <br />
He has published in academic journals as well as the popular press and has been involved in the organization of a range of teaching courses, master classes, competitions, workshops and other events throughout Europe. He now combines his writing, teaching, research and management skills in his work for the Pilot Plant, advising on ways to encourage reflection in research and to strengthen stakeholder engagement.<br />
</p></td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/1/17/Daan.png" width="140" height="180" align="right" valign="bottom"/></td><br />
</tr><br />
</table><br />
<center><br />
<br />
<br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' height=140 width=195 /></a></td><br />
</tr><table width="100%" > <br />
<tr><br />
<td colspan="2" align="left"><h3><br/>Meeting of Young Minds</h3><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<p>Together with the Rathenau Institute, our team will organize one of the two debate rounds at the event Meeting of Young Minds. This debate will take place the Friday of the Jamboree, October 5th. The topic of this debate will be about the release of research details on the creation of highly transmissible H5N1 (bird flu) in the lab. With different experts we will discuss different statements like:<br />
<br/><br />
<br/><br />
• The NSABB made the right choice to give permission for publication of this research<br />
<br/><br />
• Looking at the potential risks, this research should not have started in the first place (accidents in the past, e.g. 1977 pandemic of H1N1, which probably escaped from the lab)<br />
<br/><br />
• The scientific community has to remain ‘open access’ – restricting access to scientific literature hampers the progress in science. <br />
<br/><br />
<br/><br />
During this debate the public will get also a chance to express their opinion. So please come and be part of this interesting debate!<br />
</p><br />
</td><br />
</tr><br />
<tr><br />
<br />
</table><br />
</center><br />
</div><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-09-25T21:01:50Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/8/88/Logoigemklein.png" border="0" width="100" height="100"></a></div><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/2/26/HumanPractice.jpg" align="middle" width="100%"><br />
<br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<br />
<br/><br/><br />
<h2>Human practice</h2><br />
<p>Our team focused on several part of the category called human practise. We were in a very good<br />
collaboration with a MSc student in Educational studies named Amalia Ephrat. During the brainstorm<br />
sessions the team helped her to observe collaborative learning activities.<br />
<br/><br />
<br/><br />
We are also part of a documentary called Lab-Life, which is filmed by Frank Theys. In this<br />
documentary he follows the daily life of the scientific research project of our team. For this<br />
documentary an embedded humanist, Daan Schuurbiers was partly involved with our p roject. His<br />
professional view on social sciences helped our team a lot.<br />
<br/><br />
<br/><br />
Furthermore, during the European jamboree TUDelft 2012 iGEM team will organize together with the Rathenau<br />
Institute a debate called Meeting of Young Minds. The subject of this debate will be the H5N1 virus<br />
and weather the research manuscript should have been published. This will be a very interesting<br />
debate with different experts, the team and of course the audience!<br />
</p><br />
<table width="100%" > <br />
<tr><br />
<td colspan="2" align="left"><h3>Collaborative learning</h3><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<p>During the brainstorm sessions a MSc student in Educational studies, Amalia Ephrat had recorded the way this team came to their final topic Snifferomyces! The team helped her to study the collaborative learning activities between students with different international backgrounds within the learning context of the University</p><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2" align="left"><br/><h3>Who is Amalia Ephrat? – Our MSc students in Educational studies</h3><br />
</td><br />
</tr><br />
<tr><br />
<td><br />
<p>Amalia Ephrat is a MSc student in Educational studies at Leiden, she<br />
did a short internship focused on collaborative learning<br />
activities between students with an international background within<br />
the learning context of the university.<br />
<br/><br />
<br/><br />
When students of diverse backgrounds participate in a project where<br />
collaborative learning is important, the individual differences can<br />
pose a series of challenges to the group processes. This is a well-<br />
known challenge for many Dutch universities, which makes it a relevant<br />
topic for educational research to investigate the means for<br />
intervention and the effects of those interventions on collaborative<br />
learning processes and outcomes.<br />
<br/><br />
<br/><br />
Her plan is to improve collaborative learning amongst students of<br />
different backgrounds, by designing research and conduct measurement<br />
during the brainstorming phase of the project. Research shall consist<br />
of qualitative exploratory methods using observational methods and<br />
interviews and quantitative research using several questionnaires,<br />
including collaborative skills, empathy and intercultural conflict<br />
management.<br />
<br/><br />
<br/><br />
The main focus of her research is the collaborative process in the<br />
iGEM group and the efficacy of the interventions of the supervisors to<br />
support the collaborative process in a culturally diverse group of<br />
students.<br />
</p><br />
</td><br />
<br />
<td><img src="https://static.igem.org/mediawiki/igem.org/d/d2/Amalia3.jpg" align="right" valign="bottom" /></td><br />
</tr><br />
</table><br />
<br />
<center><br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/4/4b/Amalia01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/4/4b/Amalia01.jpg' height=120 width=140 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/8/81/Amalia02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/8/81/Amalia02.jpg' height=120 width=160 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/6/67/Amalia03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/6/67/Amalia03.jpg' height=120 width=140 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/d/d6/Amalia04.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/d/d6/Amalia04.jpg' height=120 width=140 /></a></td><br />
</tr><br />
</table><br />
</center><br />
<br />
<br/><br />
<br />
<table width="100%" > <br />
<tr><br />
<td colspan="2" align="left"><h3>Documentary Lab-Life</h3><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<p>The TU Delft 2012 team will be on seen on Belgian, Dutch and German television next year! During this project a Flemish documentary film director, Frank Theys was filming the team for his documentary Lab-Life. This full-length documentary is focused on how modern scientific research is being carried out, from the idea-conception through research, to results and publication. This documentary will become a real international scope on research, including multicultural aspects.<br />
<br/><br />
<br/><br />
Frank Theys started to record our team from the very beginning. The film director recorded many brainstorm sessions, and followed us till the final topic, Snifferomyces! Knowing what this project will be about, he started to film the amazing lab team while preforming experiments, but also the modellers who explain the importance of their contribution in the scientific world. And will film the final presentation at the Jamboree. Furthermore another interesting part of this documentary will be the focus on societal implications. The problems what comes with scientific research and the solutions and breakthroughs will be shown to a very brought audience on the television senders NOS, VRT and ZDF next year. <br />
<br/><br />
<br/><br />
By participating in this documentary our team will let a broad audience know about the daily life in the laboratory in the fields of the new technologies (NBIC). The team will inform people about what scientific research is about today. This means more than just doing lab work. Also other daily aspects that are connected to the research were filmed by Frank, like funding, public relations, social events, the team’s expectations of the research and possible applications, basically the whole biotope around a modern research team.<br />
<br/><br/><br />
We are the first iGEM team that a documentary has been done for it. Thus, the film may constitute a useful material for the following iGEM teams!!!!<br />
</p><br />
</td><br />
</tr><br />
<tr><br />
</td><br />
</tr><br />
<tr><br />
<td><br />
<p><br />
Our team had extra help from an embedded humanist, named Daan Schuurbiers, who followed the research as a midstream modulation project. Including Daan to the project, the team became also aware of the social sciences of the research. ‘’Midstream modulation asks how research is to be carried out, which is the main business of research, rather than whether a research project should be carried out, which is an upstream policy question. It is a means to evaluate and adjust research decisions in light of societal factors while the research process is taking place.’’ There are 3 different stages in the governance of science and technology, upstream, downstream and midstream modulation, see figure on the right. So by thinking about midstream modulation, this project is connected with the scientific research as well as to the social issues. In this documentary you will see how science will meet the human interest in many ways. <br />
<br/><br />
<h6>D. Schuurbiers, E. Fisher (2009), Lab-scale intervention. Science & Society Series on Convergence Research, EMBO reports VOL 10 NO 5</h6><br />
<br />
<td><img src="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" width="140" height="180" align="right" valign="bottom" /></td><br />
</tr><br />
<td colspan="2" align="left"><h3><br/>Who is Frank Theys? – Our film director</h3><br />
</td><br />
</tr><br />
<tr><br />
<td><br />
<p><br />
Frank Theys is a film and theatre director and visual artist. His work has been shown worldwide and belongs to the collections of a.o. the Museum of Modern Art (New York) and the Centre National de la Cinématographie (Paris). He received several international awards and the honourable title of Cultural Ambassador of Flanders. Currently he works on a documentary film called 'Lab-Life' in which he follows the daily life around a few scientific research projects. One of these projects is the iGEM team of TUDelft that he considers as an ideal project to introduce the world of science to a broad audience. <br />
Frank Theys has an MD in Philosophy and is currently doing a PhD in the Arts at the KULeuven. He teaches media art at the St-Lucas Art Academy in Ghent and art philosophy at the ArtScience Interfaculty at the Royal Art Academy in Den Hague. <br />
</p><br />
</td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/2/2b/Frank.png" width="140" height="180" align="right" valign="bottom" /></td><br />
</tr><br />
<center><br />
</table><br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/c/c0/Frank01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/c/c0/Frank01.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/b/b2/Frank02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/b/b2/Frank02.jpg' height=85 width=100 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/e/eb/Frank03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/e/eb/Frank03.jpg' height=85 width=100 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/3/38/Frank04.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/3/38/Frank04.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/9/91/Frank05.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/9/91/Frank05.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/3/3b/Frank06.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/3/3b/Frank06.jpg' height=90 width=98 /></a></td><br />
</tr><br />
</table><br />
</center><br />
<br/><br />
<table width="100%" ><br />
<tr><br />
<td colspan="2" align="left"><h3><br/>Who is Daan Schuurbiers? – Our embedded humanist</h3><br />
<br />
<tr><br />
<br />
<td><br />
<p><br />
Daan Schuurbiers is director of the Pilot Plant (De Proeffabriek), consultancy for responsible innovation. Daan studied chemistry and philosophy at the University of Amsterdam and has a PhD in ethics of technology from Delft University of Technology. His work centers on the social and ethical dimensions of newly emerging science and technologies. Daan's research efforts have focused on the design of new forms of dialogue between social and natural scientists, enhancing socio-ethical reflection in early stages of research. In addition to teaching and research, Daan has extensive experience in project management and consultancy, particularly in the area of dialogue and engagement with science and technology. <br />
He has published in academic journals as well as the popular press and has been involved in the organization of a range of teaching courses, master classes, competitions, workshops and other events throughout Europe. He now combines his writing, teaching, research and management skills in his work for the Pilot Plant, advising on ways to encourage reflection in research and to strengthen stakeholder engagement.<br />
</p></td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/1/17/Daan.png" width="140" height="180" align="right" valign="bottom"/></td><br />
</tr><br />
</table><br />
<center><br />
<br />
<br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' height=140 width=195 /></a></td><br />
</tr><table width="100%" > <br />
<tr><br />
<td colspan="2" align="left"><h3><br/>Meeting of Young Minds</h3><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<p>Together with the Rathenau Institute, our team will organize one of the two debate rounds at the event Meeting of Young Minds. This debate will take place the Friday of the Jamboree, October 5th. The topic of this debate will be about the release of research details on the creation of highly transmissible H5N1 (bird flu) in the lab. With different experts we will discuss different statements like:<br />
<br/><br />
<br/><br />
• The NSABB made the right choice to give permission for publication of this research<br />
• Looking at the potential risks, this research should not have started in the first place (accidents in the past, e.g. 1977 pandemic of H1N1, which probably escaped from the lab)<br />
• The scientific community has to remain ‘open access’ – restricting access to scientific literature hampers the progress in science. <br />
<br/><br />
<br/><br />
During this debate the public will get also a chance to express their opinion. So please come and be part of this interesting debate!<br />
</p><br />
</td><br />
</tr><br />
<tr><br />
<br />
</table><br />
</center><br />
</div><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-09-24T20:33:57Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/e/e2/Igemlogo.png" border="0" width="100" height="100"></a></div><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/2/26/HumanPractice.jpg" align="middle" width="100%"><br />
<br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<br />
<br/><br/><br />
<h2>Human practice</h2><br />
<p>Our team focused on several part of the category called human practise. We were in a very good<br />
collaboration with a MSc student in Educational studies named Amalia Ephrat. During the brainstorm<br />
sessions the team helped her to observe collaborative learning activities.<br />
<br/><br />
<br/><br />
We are also part of a documentary called Lab-Life, which is filmed by Frank Theys. In this<br />
documentary he follows the daily life of the scientific research project of our team. For this<br />
documentary an embedded humanist, Daan Schuurbiers was partly involved with our p roject. His<br />
professional view on social sciences helped this team a lot.<br />
<br/><br />
<br/><br />
Furthermore, during the European jamboree this team will organize together with the Rathenau<br />
Institute a debate called Meeting of Young Minds. The subject of this debate will be the H5N1 virus<br />
and weather the research manuscript should have been published. This will be a very interesting<br />
debate with different experts, the team and of course the audience!<br />
</p><br />
<table width="100%" > <br />
<tr><br />
<td colspan="2" align="left"><h3>Collaborative learning</h3><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<p>During the brainstorm sessions a MSc student in Educational studies, Amalia Ephrat had recorded the way this team came to their final topic Snifferomyces! The team helped her to study the collaborative learning activities between students with different international backgrounds within the learning context of the University</p><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2" align="left"><h3>Who is Amalia Ephrat? – Our MSc students in Educational studies</h3><br />
</td><br />
</tr><br />
<tr><br />
<td><br />
<p>Amalia Ephrat is a MSc student in Educational studies at Leiden, she<br />
did a short internship focused on collaborative learning<br />
activities between students with an international background within<br />
the learning context of the university.<br />
<br/><br />
<br/><br />
When students of diverse backgrounds participate in a project where<br />
collaborative learning is important, the individual differences can<br />
pose a series of challenges to the group processes. This is a well-<br />
known challenge for many Dutch universities, which makes it a relevant<br />
topic for educational research to investigate the means for<br />
intervention and the effects of those interventions on collaborative<br />
learning processes and outcomes.<br />
<br/><br />
<br/><br />
Her plan is to improve collaborative learning amongst students of<br />
different backgrounds, by designing research and conduct measurement<br />
during the brainstorming phase of the project. Research shall consist<br />
of qualitative exploratory methods using observational methods and<br />
interviews and quantitative research using several questionnaires,<br />
including collaborative skills, empathy and intercultural conflict<br />
management.<br />
<br/><br />
<br/><br />
The main focus of her research is the collaborative process in the<br />
iGEM group and the efficacy of the interventions of the supervisors to<br />
support the collaborative process in a culturally diverse group of<br />
students.<br />
</p><br />
</td><br />
<br />
<td><img src="https://static.igem.org/mediawiki/igem.org/d/d2/Amalia3.jpg" align="right" valign="bottom" /></td><br />
</tr><br />
</table><br />
<br />
<center><br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/4/4b/Amalia01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/4/4b/Amalia01.jpg' height=120 width=140 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/8/81/Amalia02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/8/81/Amalia02.jpg' height=120 width=160 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/6/67/Amalia03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/6/67/Amalia03.jpg' height=120 width=140 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/d/d6/Amalia04.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/d/d6/Amalia04.jpg' height=120 width=140 /></a></td><br />
</tr><br />
</table><br />
</center><br />
<br />
<br/><br />
<br />
<table width="100%" > <br />
<tr><br />
<td colspan="2" align="left"><h3>Documentary Lab-Life</h3><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<p>The TU Delft 2012 team will be on seen on Belgian, Dutch and German television next year! During this project a Flemish documentary film director, Frank Theys was filming the team for his documentary Lab-Life. This full-length documentary is focused on how modern scientific research is being carried out, from the idea-conception through research, to results and publication. This documentary will become a real international scope on research, including multicultural aspects.<br />
<br/><br />
<br/><br />
Frank Theys started to record the team from the very beginning. The film director recorded many brainstorm sessions, and followed us till the final topic, Snifferomyces! Knowing what this project will be about, he started to film the amazing lab team while preforming experiments, but also the modellers who explain the importance of their contribution in the scientific world. And will film the final presentation at the Jamboree. Furthermore another interesting part of this documentary will be the focus on societal implications. The problems what comes with scientific research and the solutions and breakthroughs will be shown to a very brought audience on the television senders NOS, VRT and ZDF next year. <br />
<br/><br />
<br/><br />
By participating in this documentary this team will let a broad audience know about the daily life in the laboratory in the fields of the new technologies (NBIC). The team will inform people about what scientific research is about today. This means more than just doing lab work. Also other daily aspects that are connected to the research were filmed by Frank, like funding, public relations, social events, the team’s expectations of the research and possible applications, basically the whole biotope around a modern research team.<br />
</p><br />
</td><br />
</tr><br />
<tr><br />
</td><br />
</tr><br />
<tr><br />
<td><br />
<p><br />
This team had extra help from an embedded humanist, named Daan Schuurbiers, who followed the research as a midstream modulation project. Including Daan to the project, the team became also aware of the social sciences of the research. ‘’Midstream modulation asks how research is to be carried out, which is the main business of research, rather than whether a research project should be carried out, which is an upstream policy question. It is a means to evaluate and adjust research decisions in light of societal factors while the research process is taking place.’’ There are 3 different stages in the governance of science and technology, upstream, downstream and midstream modulation, see figure on the right. So by thinking about midstream modulation, this project is connected with the scientific research as well as to the social issues. In this documentary you will see how science will meet the human interest in many ways. <br />
<br/><br />
[D. Schuurbiers, E. Fisher (2009), Lab-scale intervention. Science & Society Series on Convergence Research, EMBO reports VOL 10 NO 5]<br />
<br />
<td><img src="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" width="140" height="180" align="right" valign="bottom" /></td><br />
</tr><br />
<td colspan="2" align="left"><h3>Who is Frank Theys? – Our film director</h3><br />
</td><br />
</tr><br />
<tr><br />
<td><br />
<p><br />
Frank Theys is a film and theatre director and visual artist. His work has been shown worldwide and belongs to the collections of a.o. the Museum of Modern Art (New York) and the Centre National de la Cinématographie (Paris). He received several international awards and the honourable title of Cultural Ambassador of Flanders. Currently he works on a documentary film called 'Lab-Life' in which he follows the daily life around a few scientific research projects. One of these projects is the iGEM team of TUDelft that he considers as an ideal project to introduce the world of science to a broad audience. <br />
Frank Theys has an MD in Philosophy and is currently doing a PhD in the Arts at the KULeuven. He teaches media art at the St-Lucas Art Academy in Ghent and art philosophy at the ArtScience Interfaculty at the Royal Art Academy in Den Hague. <br />
</p><br />
</td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/2/2b/Frank.png" width="140" height="180" align="right" valign="bottom" /></td><br />
</tr><br />
<center><br />
</table><br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/c/c0/Frank01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/c/c0/Frank01.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/b/b2/Frank02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/b/b2/Frank02.jpg' height=85 width=100 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/e/eb/Frank03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/e/eb/Frank03.jpg' height=85 width=100 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/3/38/Frank04.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/3/38/Frank04.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/9/91/Frank05.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/9/91/Frank05.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/3/3b/Frank06.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/3/3b/Frank06.jpg' height=90 width=98 /></a></td><br />
</tr><br />
</table><br />
</center><br />
<br/><br />
<table width="100%" ><br />
<tr><br />
<td colspan="2" align="left"><h3>Who is Daan Schuurbiers? – Our embedded humanist</h3><br />
<br />
<tr><br />
<br />
<td><br />
<p><br />
Daan Schuurbiers is director of the Pilot Plant (De Proeffabriek), consultancy for responsible innovation. Daan studied chemistry and philosophy at the University of Amsterdam and has a PhD in ethics of technology from Delft University of Technology. His work centers on the social and ethical dimensions of newly emerging science and technologies. Daan's research efforts have focused on the design of new forms of dialogue between social and natural scientists, enhancing socio-ethical reflection in early stages of research. In addition to teaching and research, Daan has extensive experience in project management and consultancy, particularly in the area of dialogue and engagement with science and technology. <br />
He has published in academic journals as well as the popular press and has been involved in the organization of a range of teaching courses, master classes, competitions, workshops and other events throughout Europe. He now combines his writing, teaching, research and management skills in his work for the Pilot Plant, advising on ways to encourage reflection in research and to strengthen stakeholder engagement.<br />
</p></td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/1/17/Daan.png" width="140" height="180" align="right" valign="bottom"/></td><br />
</tr><br />
</table><br />
<center><br />
<br />
<br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' height=140 width=195 /></a></td><br />
</tr><table width="100%" > <br />
<tr><br />
<td colspan="2" align="left"><h3>Meeting of Young Minds</h3><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<p>[Under construction]</p><br />
</td><br />
</tr><br />
<tr><br />
<br />
</table><br />
</center><br />
</div><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/3/37/Footer_2.jpg" align="middle" width="690"><br />
<a href='https://2012.igem.org/Main_Page' target="_blank"><div id='logo_igem2'></div><a/> </body></html></div>Stephanielubbershttp://2012.igem.org/Team:TU-Delft/HPTeam:TU-Delft/HP2012-09-24T20:32:53Z<p>Stephanielubbers: </p>
<hr />
<div>{{:Team:TUDelft/Scripts}}{{:Team:TUDelft/CSS}}{{:Team:TUDelft/menu}}<br />
<html><br />
<head><title>Human Practice</title><br />
<body><br />
<div style="height:70px; width:100%;"></div> <br />
<img src="https://static.igem.org/mediawiki/igem.org/7/74/Background_greenlamp.jpg" class="bg_team"><br />
<div id="logo_ed"><a href="https://2012.igem.org/Team:TU-Delft" 'onfocus=this.blur()'><img src="https://static.igem.org/mediawiki/igem.org/e/e2/Igemlogo.png" border="0" width="100" height="100"></a></div><br />
<br />
<img src="https://static.igem.org/mediawiki/igem.org/2/26/HumanPractice.jpg" align="middle" width="100%"><br />
<br />
<div id="contentbox" style="text-align:justify;"><br />
<br />
<br />
<br/><br/><br />
<h2>Human practice</h2><br />
<p>Our team focused on several part of the category called human practise. We were in a very good<br />
collaboration with a MSc student in Educational studies named Amalia Ephrat. During the brainstorm<br />
sessions the team helped her to observe collaborative learning activities.<br />
<br/><br />
<br/><br />
We are also part of a documentary called Lab-Life, which is filmed by Frank Theys. In this<br />
documentary he follows the daily life of the scientific research project of our team. For this<br />
documentary an embedded humanist, Daan Schuurbiers was partly involved with our p roject. His<br />
professional view on social sciences helped this team a lot.<br />
<br/><br />
<br/><br />
Furthermore, during the European jamboree this team will organize together with the Rathenau<br />
Institute a debate called Meeting of Young Minds. The subject of this debate will be the H5N1 virus<br />
and weather the research manuscript should have been published. This will be a very interesting<br />
debate with different experts, the team and of course the audience!<br />
</p><br />
<table width="100%" > <br />
<tr><br />
<td colspan="2" align="left"><h3>Collaborative learning</h3><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<p>During the brainstorm sessions a MSc student in Educational studies, Amalia Ephrat had recorded the way this team came to their final topic Snifferomyces! The team helped her to study the collaborative learning activities between students with different international backgrounds within the learning context of the University</p><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2" align="left"><h3>Who is Amalia Ephrat? – Our MSc students in Educational studies</h3><br />
</td><br />
</tr><br />
<tr><br />
<td><br />
<p>Amalia Ephrat is a MSc student in Educational studies at Leiden, she<br />
did a short internship focused on collaborative learning<br />
activities between students with an international background within<br />
the learning context of the university.<br />
<br/><br />
<br/><br />
When students of diverse backgrounds participate in a project where<br />
collaborative learning is important, the individual differences can<br />
pose a series of challenges to the group processes. This is a well-<br />
known challenge for many Dutch universities, which makes it a relevant<br />
topic for educational research to investigate the means for<br />
intervention and the effects of those interventions on collaborative<br />
learning processes and outcomes.<br />
<br/><br />
<br/><br />
Her plan is to improve collaborative learning amongst students of<br />
different backgrounds, by designing research and conduct measurement<br />
during the brainstorming phase of the project. Research shall consist<br />
of qualitative exploratory methods using observational methods and<br />
interviews and quantitative research using several questionnaires,<br />
including collaborative skills, empathy and intercultural conflict<br />
management.<br />
<br/><br />
<br/><br />
The main focus of her research is the collaborative process in the<br />
iGEM group and the efficacy of the interventions of the supervisors to<br />
support the collaborative process in a culturally diverse group of<br />
students.<br />
</p><br />
</td><br />
<br />
<td><img src="https://static.igem.org/mediawiki/igem.org/d/d2/Amalia3.jpg" align="right" valign="bottom" /></td><br />
</tr><br />
</table><br />
<br />
<center><br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/4/4b/Amalia01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/4/4b/Amalia01.jpg' height=120 width=140 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/8/81/Amalia02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/8/81/Amalia02.jpg' height=120 width=160 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/6/67/Amalia03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/6/67/Amalia03.jpg' height=120 width=140 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/d/d6/Amalia04.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/d/d6/Amalia04.jpg' height=120 width=140 /></a></td><br />
</tr><br />
</table><br />
</center><br />
<br />
<br/><br />
<br />
<table width="100%" > <br />
<tr><br />
<td colspan="2" align="left"><h3>Documentary Lab-Life</h3><br />
</td><br />
</tr><br />
<tr><br />
<td colspan="2"><br />
<p>The TU Delft 2012 team will be on seen on Belgian, Dutch and German television next year! During this project a Flemish documentary film director, Frank Theys was filming the team for his documentary Lab-Life. This full-length documentary is focused on how modern scientific research is being carried out, from the idea-conception through research, to results and publication. This documentary will become a real international scope on research, including multicultural aspects.<br />
<br/><br />
<br/><br />
Frank Theys started to record the team from the very beginning. The film director recorded many brainstorm sessions, and followed us till the final topic, Snifferomyces! Knowing what this project will be about, he started to film the amazing lab team while preforming experiments, but also the modellers who explain the importance of their contribution in the scientific world. And will film the final presentation at the Jamboree. Furthermore another interesting part of this documentary will be the focus on societal implications. The problems what comes with scientific research and the solutions and breakthroughs will be shown to a very brought audience on the television senders NOS, VRT and ZDF next year. <br />
<br/><br />
<br/><br />
By participating in this documentary this team will let a broad audience know about the daily life in the laboratory in the fields of the new technologies (NBIC). The team will inform people about what scientific research is about today. This means more than just doing lab work. Also other daily aspects that are connected to the research were filmed by Frank, like funding, public relations, social events, the team’s expectations of the research and possible applications, basically the whole biotope around a modern research team.<br />
</p><br />
</td><br />
</tr><br />
<tr><br />
</td><br />
</tr><br />
<tr><br />
<td><br />
<p><br />
This team had extra help from an embedded humanist, named Daan Schuurbiers, who followed the research as a midstream modulation project. Including Daan to the project, the team became also aware of the social sciences of the research. ‘’Midstream modulation asks how research is to be carried out, which is the main business of research, rather than whether a research project should be carried out, which is an upstream policy question. It is a means to evaluate and adjust research decisions in light of societal factors while the research process is taking place.’’ There are 3 different stages in the governance of science and technology, upstream, downstream and midstream modulation, see figure on the right. So by thinking about midstream modulation, this project is connected with the scientific research as well as to the social issues. In this documentary you will see how science will meet the human interest in many ways. <br />
<br/><br />
[D. Schuurbiers, E. Fisher (2009), Lab-scale intervention. Science & Society Series on Convergence Research, EMBO reports VOL 10 NO 5]<br />
<br />
<td><img src="https://static.igem.org/mediawiki/igem.org/3/3d/Upstream.png" width="140" height="180" align="right" valign="bottom" /></td><br />
</tr><br />
<td colspan="2" align="left"><h3>Who is Frank Theys? – Our film director</h3><br />
</td><br />
</tr><br />
<tr><br />
<td><br />
<p><br />
Frank Theys is a film and theatre director and visual artist. His work has been shown worldwide and belongs to the collections of a.o. the Museum of Modern Art (New York) and the Centre National de la Cinématographie (Paris). He received several international awards and the honourable title of Cultural Ambassador of Flanders. Currently he works on a documentary film called 'Lab-Life' in which he follows the daily life around a few scientific research projects. One of these projects is the iGEM team of TUDelft that he considers as an ideal project to introduce the world of science to a broad audience. <br />
Frank Theys has an MD in Philosophy and is currently doing a PhD in the Arts at the KULeuven. He teaches media art at the St-Lucas Art Academy in Ghent and art philosophy at the ArtScience Interfaculty at the Royal Art Academy in Den Hague. <br />
</p><br />
</td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/2/2b/Frank.png" width="140" height="180" align="right" valign="bottom" /></td><br />
</tr><br />
<center><br />
</table><br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/c/c0/Frank01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/c/c0/Frank01.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/b/b2/Frank02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/b/b2/Frank02.jpg' height=85 width=100 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/e/eb/Frank03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/e/eb/Frank03.jpg' height=85 width=100 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/3/38/Frank04.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/3/38/Frank04.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/9/91/Frank05.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/9/91/Frank05.jpg' height=90 width=98 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/3/3b/Frank06.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/3/3b/Frank06.jpg' height=90 width=98 /></a></td><br />
</tr><br />
</table><br />
</center><br />
<br/><br />
<table width="100%" ><br />
<tr><br />
<td colspan="2" align="left"><h3>Who is Daan Schuurbiers? – Our embedded humanist</h3><br />
<br />
<tr><br />
<br />
<td><br />
<p><br />
Daan Schuurbiers is director of the Pilot Plant (De Proeffabriek), consultancy for responsible innovation. Daan studied chemistry and philosophy at the University of Amsterdam and has a PhD in ethics of technology from Delft University of Technology. His work centers on the social and ethical dimensions of newly emerging science and technologies. Daan's research efforts have focused on the design of new forms of dialogue between social and natural scientists, enhancing socio-ethical reflection in early stages of research. In addition to teaching and research, Daan has extensive experience in project management and consultancy, particularly in the area of dialogue and engagement with science and technology. <br />
He has published in academic journals as well as the popular press and has been involved in the organization of a range of teaching courses, master classes, competitions, workshops and other events throughout Europe. He now combines his writing, teaching, research and management skills in his work for the Pilot Plant, advising on ways to encourage reflection in research and to strengthen stakeholder engagement.<br />
</p></td><br />
<td><img src="https://static.igem.org/mediawiki/igem.org/1/17/Daan.png" width="140" height="180" align="right" valign="bottom"/></td><br />
</tr><br />
</table><br />
<center><br />
<br />
<br />
<table width="100%" > <br />
<tr><td><a href='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/9/9c/Daan01.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/a/a7/Daan02.jpg' height=140 width=195 /></a></td><br />
<td><a href='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' rel="lightbox" target="_blank"><img src='https://static.igem.org/mediawiki/igem.org/2/29/Daan03.jpg' height=140 width=195 /></a></td><br />
</tr><br />
</table><br />
</center><br />
</div><br />
<br />
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<table width="100%" > <br />
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<td colspan="2" align="left"><h3>Meeting of Young Minds</h3><br />
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<p>[Under construction]</p><br />
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