Team:St Andrews

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<html><h1>University of St Andrews 2010 iGEM Team</h1>
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Welcome to the the University of St Andrews <a href="https://2010.igem.org/Main_Page"> iGEM 2010</a> Team Website. We are the first University of St Andrews iGEM Team. Our work is mainly based on Quorum Sensing and trying to investigate possible applications in Synthetic Biology.
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<img border="0" src="https://static.igem.org/mediawiki/igem.org/e/e9/Standrewsheader.JPG" width="950" height="175" />
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<li class="ly"><a class="ry" href="https://2010.igem.org/Team:St_Andrews">Home</a></li>
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<li class="ly"><a class="ly" href="http://www.st-andrews.ac.uk/~igem2010/blog/">BLOG</a></li>
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<li class="ly"><a class="ly" href="#contact">Contact</a></li>
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<li class="ly"><a class="ly" href="#about">About</a></li>
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<p class="padding">Our multidisciplinary team is the first to hail from St Andrews University, consisting of biology students: Dave and Sarah, medical students: Rachael and Fatimeh, physicists: Alasdair and Patrick, computer scientist Jaunty, chemist Jim and biochemist Lukas. We are overseen by advisors Olivia, Anne, Wim, Chris and Michael.</p>
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<td width="260"> Comprised of 9 undergraduate <a href="https://2010.igem.org/Team:St Andrews/team/members">students</a> and guided by 5 <a href="https://2010.igem.org/Team:St Andrews/advisors">advisors</a>, our team stems from a variety of different scientific fields: Medicine, Biological Sciences, Chemistry, Computer Science and Physics.</td>
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<td>Cholera is a bacterial disease that infects approximately 5 million people worldwide each year, approximately 100,000 of which are fatal. Symptoms of an acute cholera infection including diarrhoea and severe dehydration that can kill within hours if left untreated. <br/>
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<h1>The Problem</h1>
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Provision of safe water is critical to preventing cholera outbreaks however in many cases this is not feasible, particularly in areas recently hit by natural disaster. Our project involves investigating the basic science behind a potential means of preventing the disease through the application of synthetic biology. Lately Cholera outbreaks occurred in Pakistan and Haiti. In Haiti around 3500 confirmed causes have been reported <a href="http://www.elpais.com/articulo/internacional/Haiti/lucha/reloj/frenar/epidemia/colera/elpepiint/20101025elpepiint_5/Tes">news in spanish</a> and <a href="http://www.bbc.co.uk/news/world-latin-america-11632738">news in english</a>. Read more about our <a href="https://2010.igem.org/Team:St Andrews/project/objectives"> project</a>. </td>
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<p class="padding">The St Andrews iGEM team plan is to do something useful with quorum sensing – the method by which bacteria make decisions in a cell density dependent manner. They do this by secreting autoinducer molecules, which diffuse back into the cells and regulate their own biosynthesis. Certain concentrations of autoinducer represent to a bacterium an amount of fellow-bacteria in the environment and the response is activation or deactivation of a set of genes.
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We are interested in the quorum sensing system of Vibrio cholerae, the bacterium understood to be responsible for the deadly diarrhoeal disease, <i>cholera</i>. <i>Cholera</i> is extremely rare in the developed world, but in areas with poor sanitation it affects people who drink unsafe water. Young children are the most at risk, and left untreated death can occur by dehydration. According to the WHO, cholera kills between 100,000 and 120,000 people every year. Efforts have been made towards an effective cholera vaccine suitable for young children, but they have not yet been successful. It is now suggested that synthetic probiotic bacteria could be a safe and economical way to confer resistance to cholera.</p>
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<h1>Quorum Sensing in V. Cholerae</h1>
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<p class="padding">Most <i>cholera</i> cells are killed off by stomach acid, but those that remain alive attach to the gut wall and multiply. At this low cell density, autoinducer concentration is low, and virulence factors are expressed. Once high cell density is reached, enough toxin is present to cause severe diarrhoea. At this point, the autoinducer concentration is high, and virulence factors are repressed. The now avirulent V. Cholerae detach from the gut wall and are flushed out of the body to infect a new host.
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Our idea is to synthesise <i>Escherichia coli</i> bacteria that will use this ingenious mechanism to communicate with <i>Vibrio cholerae</i>. Our engineered <i>Escherichia coli</i> will harmlessly colonise the gut, and in large numbers secrete the cholera autoinducer, CAI-1. This will cause an immediate high autoinducer concentration to be detected by incoming <i>Vibrio cholerae</i> cells which then become avirulent and harmlessly pass out of the body.</p>
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<h1>Our Plan</h1>
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<td width="260"> We would like to thank our <a href="https://2010.igem.org/Team:St Andrews/team/sponsors">sponsors </a>: multiple faculties of the University of St Andrews, biotech companies, etc., whose generosity has made this all possible.</td>
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<p class="padding">The wet work will focus on two challenges. The first being to add new functionality to the signalling parts present in the registry by re-engineering the existing <i>LuxR</i> quorum sensing system to create a bistable switch. This will allow us to infer a signalling molecule concentration required to deactivate the system much lower than the concentration required to activate it. We will characterise this system by using a fluorescent protein reporter and measuring fluorescence at different cell densities. The second challenge will be adding the cholera autoinducer synthase gene CqsA to <i>Escherichia coli</i> so that CAI-1 is secreted. The eventual aim is that the bistable switching system will be used to control CqsA expression, so that the ability to compete with other bacteria in the human gut is not compromised by this metabolic burden.  
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The computational side of the team are focusing on generating ordinary differential equations to model quorum sensing in <i>Vibrio cholerae</i> and on modelling more complex problems such as bistability and multiple quorum loops working in tandem of our parts.</p>
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Part of our project is also to help other iGEM teams (both current and future) by fine-tunning the control over protein expression by designing new ribosome binding sites.
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We collaborated in iGEM 2010 with multiple teams in multiple contexts (wiki development (<a href="https://2010.igem.org/Team:TU_Delft">Delft</a> team), human practices data collection, exhange of DNA (<a href="https://2010.igem.org/Team:Sheffield">Sheffield</a> team)...).
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In order to complete our project several biobricks must be constructed. Through use of standard protocols and procedures we plan to construct a bistable switch based on the Lux quorum sensing system and a CAI-1 sender using the cqsa gene from <i>Vibrio cholerae</i>. Follow our progress in the<a href="https://2010.igem.org/Team:St Andrews/project/laboratory"> laboratory. </a>
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<a href="https://2010.igem.org/Team:St Andrews/project/ethics">Human Practices</a> shapes the future and the very being of all science. Human Practices includes (but is not limited to) the purpose, effects and impact of science on society. A realm where ethics, economics and <i>E.coli</i> all intertwine.
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To better understand the inner workings of the <i>Vibrio cholera</i> quorum sensing system we produced a series of computational models to simulate the operation of <i>Vibrio cholerae</i>. Based upon differential equations and solved computationally via the Fourth Order Runge-Kutta method our models provide a comprehensive view of <i>Vibrio cholerae</i> quorum sensing and bi-stable switching behaviour. To find out how we designed our models from the blackboard to the CPU check out our <a href="https://2010.igem.org/Team:St Andrews/project/modelling">modelling </a>. This work is potentially a flexible framework for future quorum sensing modelling. Possible future extensions can be other diffusion models for quorum sensing, other quorum sensing systems, etc. Different models are proposed as an example.</td>
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We proposed a new solution for the fine-tuning the translation of proteins designing Ribosome Binding Site by the usage of an RBS calculator. Check out more about this <a href="https://2010.igem.org/Team:St_Andrews/project/RBS">RBS</a>.
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* [[Team:St_Andrews/FAQ | Frequently Asked Questions ]]
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* [https://igem.org/Main_Page iGEM 2010 ]

Latest revision as of 03:02, 28 October 2010


St Andrews from East Sands

University of St Andrews iGEM 2010

Welcome!

The Saints

University of St Andrews iGEM 2010

Our first year at iGEM!


University of St Andrews 2010 iGEM Team

Welcome to the the University of St Andrews iGEM 2010 Team Website. We are the first University of St Andrews iGEM Team. Our work is mainly based on Quorum Sensing and trying to investigate possible applications in Synthetic Biology.

Comprised of 9 undergraduate students and guided by 5 advisors, our team stems from a variety of different scientific fields: Medicine, Biological Sciences, Chemistry, Computer Science and Physics. Cholera is a bacterial disease that infects approximately 5 million people worldwide each year, approximately 100,000 of which are fatal. Symptoms of an acute cholera infection including diarrhoea and severe dehydration that can kill within hours if left untreated.
Provision of safe water is critical to preventing cholera outbreaks however in many cases this is not feasible, particularly in areas recently hit by natural disaster. Our project involves investigating the basic science behind a potential means of preventing the disease through the application of synthetic biology. Lately Cholera outbreaks occurred in Pakistan and Haiti. In Haiti around 3500 confirmed causes have been reported news in spanish and news in english. Read more about our project. 		We would like to thank our sponsors : multiple faculties of the University of St Andrews, biotech companies, etc., whose generosity has made this all possible.
Part of our project is also to help other iGEM teams (both current and future) by fine-tunning the control over protein expression by designing new ribosome binding sites. We collaborated in iGEM 2010 with multiple teams in multiple contexts (wiki development (Delft team), human practices data collection, exhange of DNA (Sheffield team)...).
In order to complete our project several biobricks must be constructed. Through use of standard protocols and procedures we plan to construct a bistable switch based on the Lux quorum sensing system and a CAI-1 sender using the cqsa gene from Vibrio cholerae. Follow our progress in the laboratory.
Human Practices shapes the future and the very being of all science. Human Practices includes (but is not limited to) the purpose, effects and impact of science on society. A realm where ethics, economics and E.coli all intertwine. To better understand the inner workings of the Vibrio cholera quorum sensing system we produced a series of computational models to simulate the operation of Vibrio cholerae. Based upon differential equations and solved computationally via the Fourth Order Runge-Kutta method our models provide a comprehensive view of Vibrio cholerae quorum sensing and bi-stable switching behaviour. To find out how we designed our models from the blackboard to the CPU check out our modelling . This work is potentially a flexible framework for future quorum sensing modelling. Possible future extensions can be other diffusion models for quorum sensing, other quorum sensing systems, etc. Different models are proposed as an example. We proposed a new solution for the fine-tuning the translation of proteins designing Ribosome Binding Site by the usage of an RBS calculator. Check out more about this RBS.

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