Team:Dundee
From 2012.igem.org
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<center><h2>Clostridium Difficile</h2></center> | <center><h2>Clostridium Difficile</h2></center> | ||
<em>Clostridium difficile (C. diff)</em> is a gram- positive bacterium that lives naturally in the gut. In healthy individuals, the levels of <em>C. diff</em> are kept constant as it is outcompeted by other species in the gut flora. However, when patients receive large doses of antibiotics, competing gut flora can be wiped out. This can allow numbers of <em>C. diff</em> to increase to a level where infection can be caused, resulting in severe colitis. <em>C. diff</em> has therefore become a major cause of hospital acquired infections, with, for example, some 2645 patients in hospitals in England and Wales found suffering from <em>C. diff</em> induced colitis in March- May 2010. Infection rates have also been high at Dundee's Ninewells Hospital, which is affiliated with the University of Dundee, and so for us, this is also a very local health problem. Up until now, there have been two ways of treating this problem: prescribe more antibiotics, with the added difficulty of possibly causing more resistance to build-up, or by means of faecal transplant. A faecal transplant involved the faeces of another person being transplanted directly into the patient's colon or through a drip into the stomach. This has been proven to be effective in test cases, but is obviously an unsavoury form of treatment for many patients and so the idea of creating an alternative gave rise to this project. | <em>Clostridium difficile (C. diff)</em> is a gram- positive bacterium that lives naturally in the gut. In healthy individuals, the levels of <em>C. diff</em> are kept constant as it is outcompeted by other species in the gut flora. However, when patients receive large doses of antibiotics, competing gut flora can be wiped out. This can allow numbers of <em>C. diff</em> to increase to a level where infection can be caused, resulting in severe colitis. <em>C. diff</em> has therefore become a major cause of hospital acquired infections, with, for example, some 2645 patients in hospitals in England and Wales found suffering from <em>C. diff</em> induced colitis in March- May 2010. Infection rates have also been high at Dundee's Ninewells Hospital, which is affiliated with the University of Dundee, and so for us, this is also a very local health problem. Up until now, there have been two ways of treating this problem: prescribe more antibiotics, with the added difficulty of possibly causing more resistance to build-up, or by means of faecal transplant. A faecal transplant involved the faeces of another person being transplanted directly into the patient's colon or through a drip into the stomach. This has been proven to be effective in test cases, but is obviously an unsavoury form of treatment for many patients and so the idea of creating an alternative gave rise to this project. | ||
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<center><h2>Project Summary</h2></center> | <center><h2>Project Summary</h2></center> | ||
The aim of our project is to create a new type of synthetic <em>E. coli</em>, expressing a simplified type VI secretion system that will secrete a <em>C. diff</em> specific effector, endolysin. It is hoped that the needle will either be able to puncture the <em>C. diff</em> cells and secrete the endolysin directly into the organism or that the endolysin will come into contact with the <em>C. diff</em> cell surface after secretion. We hope to prove that the new strain of <em>E. coli</em> will be able to produce enough needles on the cell surface which can then come into contact with <em>C. diff</em> cells and that enough endolysin is secreted to kill them, so in vitro experiments will be carried out to test this hypothesis. Experiments will also be set up that show that our strain of <em>E. coli</em> is able to out-compete <em>C. diff</em>, resulting in reduced numbers of the bacterium and so less chance of infection. | The aim of our project is to create a new type of synthetic <em>E. coli</em>, expressing a simplified type VI secretion system that will secrete a <em>C. diff</em> specific effector, endolysin. It is hoped that the needle will either be able to puncture the <em>C. diff</em> cells and secrete the endolysin directly into the organism or that the endolysin will come into contact with the <em>C. diff</em> cell surface after secretion. We hope to prove that the new strain of <em>E. coli</em> will be able to produce enough needles on the cell surface which can then come into contact with <em>C. diff</em> cells and that enough endolysin is secreted to kill them, so in vitro experiments will be carried out to test this hypothesis. Experiments will also be set up that show that our strain of <em>E. coli</em> is able to out-compete <em>C. diff</em>, resulting in reduced numbers of the bacterium and so less chance of infection. | ||
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<center><h2>Mathematical Modelling</h2></center> | <center><h2>Mathematical Modelling</h2></center> | ||
The depth and range of the mathematical modelling will evolve throughout this project, from models of growth for <em>Salmonella</em> and the strain of <em>E.Coli</em> that we will engineer, to systems ordinary and partial differential equations that will show us not only how two populations interact, but how the shape and natural processes of the colon affect this interaction. Other aspects that we will look at modelling are the number of "needles" that we can engineer the <em>E.Coli</em> to create and the amount of endolysin that must be secreted to lyse all of the <em>C.diff</em> bacteria. Using software such as MATLAB® and COMSOL® we are able to create visual representations of population interactions such as graphs and animations of the colon as we introduce the <em>E.Coli</em> to lyse the excessive levels of <em>C.Diff</em>. | The depth and range of the mathematical modelling will evolve throughout this project, from models of growth for <em>Salmonella</em> and the strain of <em>E.Coli</em> that we will engineer, to systems ordinary and partial differential equations that will show us not only how two populations interact, but how the shape and natural processes of the colon affect this interaction. Other aspects that we will look at modelling are the number of "needles" that we can engineer the <em>E.Coli</em> to create and the amount of endolysin that must be secreted to lyse all of the <em>C.diff</em> bacteria. Using software such as MATLAB® and COMSOL® we are able to create visual representations of population interactions such as graphs and animations of the colon as we introduce the <em>E.Coli</em> to lyse the excessive levels of <em>C.Diff</em>. | ||
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<center><h2>Software Development</h2></center> | <center><h2>Software Development</h2></center> | ||
Revision as of 08:01, 12 July 2012