Team:Uppsala University

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<font family="Cambria" size="5" color="darkred"><b>This page is currently under construction.</b></font>
 
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<i>... and that's how resistance is futile!</i>
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<h2>Project description</h2>
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<h2>The Problem</h2>
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<p>Team Uppsala University 2012 is dedicated to combating the rising antibiotic resistance in bacteria by means of synthetic biology. Old and well-known antibiotics are quickly becoming ineffective as resistance genes are spreading. Scientist around the world struggle with varying success to develop new antibacterial substances. But do we really have to abandon classic antibiotics? Team Uppsala University begs to differ, we believe new methods will allow us to combat the resistance itself, and make the bacteria once again sensitive to old drugs.</p>
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<p>The first half of the 20th century saw a revolution in the treatment of one of the major curses of mankind: pathogenic microorganisms. After the invention of first sulfa and later penicillin, through the fourties, fifties and sixties a large number of antibiotic drugs were quickly found. The age when many bacterial infections meant life-threatening epidemics were soon forgotten, as illnesses could now be cured by a few days with antibiotics. During the sixties and seventies, bacterial infections was largely considered to be a solved problem in the western world, and drug researchers turned to other areas. </p><p>
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<p>Working with real-world resistance genes isolated from ESBL outbreaks at Swedish hospitals, we are developing anti-resistance systems active at three different levels: DNA level, transcriptional level and translational level. Our systems will be delivered to the target bacteria using an engineered phage and/or a conjugative plasmid.</p>
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<p>At DNA level, we will develop a method for permanent removal of plasmids from bacteria. Using TAL Effector Nucleases, we will be able to target and cut individual resistance genes.</p>
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However, evolution is a more powerful force than one can imagine, and soon the bacterias got the upper hand. In later years, it has become clear that bacterial resistance is spreading at a faster rate than anyone could imagine. Between the seventies and late nineties, no new classes of antibiotics were launched, while usage of antibiotics continued at an ever increasing rate. This created an ideal enviroment for antibiotic resistance to spread. </p><p>
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<p>At transcriptional level, we will use synthetic super-repressors to repress transcription of resistance genes and native defense mechanisms in bacteria.</p>
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<p>At translational level, we will construct a modular large-scale screening system for sRNA:s and use it to find strongly silencing RNA sequences against three common resistance genes.</p>
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Today, it is estimated that, in the EU alone, 25 000 patients die yearly of multidrug resistant infections, which also increase health care costs by over 1.5 billion euro per year. Antibiotic research has been given higher priority in academic institutions over the last decade, but it is clear that drug development is and has been stalled for a long time.</p><p>
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<p>With this team on the project, there is no question about it: <b>Resistance is futile!</b></p>
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But do we really have to give up classic antibiotic drugs? Team Uppsala University 2012 begs to differ. We believe that new knowledge about bacterial regulatory mechanisms can enable us to once again turn resistant bacteria sensitive to classic antibiotics. This summer, we decided to show it.  
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</p>
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<h2>Latest news</h2>
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<h2>Achivements</h2>
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<b>July 22, 2012</b><br>
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Added another button below the iGEM-logo in the top right corner for those interested in <a href="https://twitter.com/igemuppsala">following us on Twitter</a>.
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<b>Working small RNAs!</b><br>
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Constructed small RNAs that can downregulate antibiotic resistance.
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<a href="https://2012.igem.org/Team:Uppsala_University/Translational">Read more</a>
<hr>
<hr>
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<b>July 21, 2012</b><br>
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The dust has finally settled from the party last night, and somehow the lab seems remarkably empty today... Anyway, new additions to the page include the top left iGEM-logo linking back to the <a href="/Main_Page">Main page</a> and a submenu of links on the <a href="/Team:Uppsala_University/Team">Team</a> page. Now where are those Aspirins...
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<b>Improved existing parts</b><br>
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Improved standard plasmid backbones from the low copy pSB4X series.
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<a href="https://2012.igem.org/Team:Uppsala_University/Backbones">Read more</a>
<hr>
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<b>July 20, 2012</b><br>
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No on-site changes today (apart from this update). However, the team is about to meet up for a barbecue in the local park – it will be awesome!
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<b>Characterized promoters</b><br>
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Characterized several promoters and their respective promoter strengths.
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<a href="https://2012.igem.org/Team:Uppsala_University/Promoters">Read more</a>
<hr>
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<b>July 19, 2012</b><br>
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New top banner and further improvements on the <a href="/Team:Uppsala_University/Team">Team</a> page. A Notebook section is also planned, which will cover our weekly endeavors.
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<b>Helped other teams</b><br>
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Our BioBricks have been requested by many iGEM teams.
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<a href="https://2012.igem.org/Team:Uppsala_University/Collaborations">Read more</a>
<hr>
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<b>July 18, 2012</b><br>
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The finalized top banner mentioned a few days ago turned out to be nothing more than wishful thinking. An improved version is currently in the making! As for how the lab work is coming along: a discussion will be held tomorrow regarding the Notebook section of the wiki, which hopefully will describe our progress in detail. More info soon!
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<b>New BioBricks</b><br>
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Constructed several new BioBricks and characterized them.
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<b>July 17, 2012</b><br>
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<a href="https://2012.igem.org/Team:Uppsala_University/Parts">Read more</a>
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Started working on our <a href="/Team:Uppsala_University/Team">Team</a> page. Meanwhile the number of Facebook likes keep increasing - thanks a lot guys, we are eternally grateful!
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<hr>
<hr>
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<b>July 16, 2012</b><br>
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Widened the top banner and will hopefully start adding more pages later today. On another note, a huge thanks to all of those liking us on Facebook. Overnight the total number went from 75 to 84, which is amazing!
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<b>Gained experience</b><br>
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<hr>
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Had a great summer while working with our iGEM project.  
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<b>July 15, 2012</b><br>
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<a href="https://2012.igem.org/Team:Uppsala_University/Notebook">Read more</a>
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Project description has been added along with a comic strip describing the general idea behind our project. We also changed the top banner, which now likely is the final version.
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<b>July 14, 2012</b><br>
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Our wiki is slowly taking form. It is being worked upon daily and once the final layout is finished we will start adding more pages. So keep checking back!<br>PS. All teams – don't forget tomorrow is the deadline for uploading your abstracts.
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<h2>The project</h2>
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<h2>Silencing sRNA</h2>
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<p id="second">In this project, Team Uppsala University will attempt to counteract the molecular machinery making a bacterium resistant to antibiotics. Using three separate methods, our hope is to silence the genes responsible for resistance accurately and effectively.</p>
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<p id="second">We have developed a modular screening system and protocol for finding silencing sRNAs against arbitrary genes. Using this, we have found strongly silencing sRNAs against a clinical antibiotic gene and lowered the minimal inhibatory concentration tenfold in resistant bacteria.  
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<p id="more"><a href="/Team:Uppsala_University/Project">Learn more</a></p>
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</p>
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<p id="more"><a href="/Team:Uppsala_University/Project#sRNA">Read more...</a>
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<h2>The competition</h2>
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<h2>New backbones</h2>
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<p id="second">The International Genetically Engineered Machine (iGEM) competition is a worldwide event hosted by MIT surrounding the area of Synthetic Biology. Once a year teams from all over the world design and execute their own projects, hoping to win the prestigious first prize.</p>
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<p id="second">We have constructed a range of new standard low copy backbones, and variants with built-in lacIq repression for tight control of toxic genes, thermosensitivity and FRT sites for removing resistance cassettes. This work was done as it turned out that the common registry pSB4 backbones all have faulty copy number regulation, while we needed low copy backbones for out project.</p>
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<p id="more"><a href="/Team:Uppsala_University/iGEM">Learn more</a></p>
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<p id="more"><a href="/Team:Uppsala_University/Backbones">Read more...</a></p>
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<h2>The university</h2>
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<h2>Chromoproteins</h2>
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<p id="second">Founded in 1477, Uppsala University is the oldest and one of the most highly regarded universities in Sweden. Throughout the years, notable people such at Carl Linnaeus and Anders Celsius have been professors at the university.</p>
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<p id="second">Proteins with a visible intrinsic color are the simplest possible reporters in molecular biology. Most iGEMers are familiar with the Red Flourescent Protein (RFP), but there are many other colors available among the organisms of the world. We have characterized and submitted new chromoproteins, allowing multiplexed colorful reporters. </p>
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<p id="more"><a href="/Team:Uppsala_University/Uppsala_University">Learn more</a></p>
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<p id="more"><a href="/Team:Uppsala_University/Chromoproteins">Read more...</a></div>
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{{Uppsala_footer}}
{{Uppsala_footer}}

Latest revision as of 02:25, 27 October 2012

Team Uppsala University – iGEM 2012


Team Uppsala University
-->


... and that's how resistance is futile!

The Problem

The first half of the 20th century saw a revolution in the treatment of one of the major curses of mankind: pathogenic microorganisms. After the invention of first sulfa and later penicillin, through the fourties, fifties and sixties a large number of antibiotic drugs were quickly found. The age when many bacterial infections meant life-threatening epidemics were soon forgotten, as illnesses could now be cured by a few days with antibiotics. During the sixties and seventies, bacterial infections was largely considered to be a solved problem in the western world, and drug researchers turned to other areas.

However, evolution is a more powerful force than one can imagine, and soon the bacterias got the upper hand. In later years, it has become clear that bacterial resistance is spreading at a faster rate than anyone could imagine. Between the seventies and late nineties, no new classes of antibiotics were launched, while usage of antibiotics continued at an ever increasing rate. This created an ideal enviroment for antibiotic resistance to spread.

Today, it is estimated that, in the EU alone, 25 000 patients die yearly of multidrug resistant infections, which also increase health care costs by over 1.5 billion euro per year. Antibiotic research has been given higher priority in academic institutions over the last decade, but it is clear that drug development is and has been stalled for a long time.

But do we really have to give up classic antibiotic drugs? Team Uppsala University 2012 begs to differ. We believe that new knowledge about bacterial regulatory mechanisms can enable us to once again turn resistant bacteria sensitive to classic antibiotics. This summer, we decided to show it.

Achivements

Working small RNAs!
Constructed small RNAs that can downregulate antibiotic resistance. Read more
Improved existing parts
Improved standard plasmid backbones from the low copy pSB4X series. Read more
Characterized promoters
Characterized several promoters and their respective promoter strengths. Read more
Helped other teams
Our BioBricks have been requested by many iGEM teams. Read more
New BioBricks
Constructed several new BioBricks and characterized them. Read more
Gained experience
Had a great summer while working with our iGEM project. Read more
 

Silencing sRNA

We have developed a modular screening system and protocol for finding silencing sRNAs against arbitrary genes. Using this, we have found strongly silencing sRNAs against a clinical antibiotic gene and lowered the minimal inhibatory concentration tenfold in resistant bacteria.

Read more...

New backbones

We have constructed a range of new standard low copy backbones, and variants with built-in lacIq repression for tight control of toxic genes, thermosensitivity and FRT sites for removing resistance cassettes. This work was done as it turned out that the common registry pSB4 backbones all have faulty copy number regulation, while we needed low copy backbones for out project.

Read more...

Chromoproteins

Proteins with a visible intrinsic color are the simplest possible reporters in molecular biology. Most iGEMers are familiar with the Red Flourescent Protein (RFP), but there are many other colors available among the organisms of the world. We have characterized and submitted new chromoproteins, allowing multiplexed colorful reporters.

Read more...


Sponsors






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