Team:St Andrews/FAQ

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> The Problem >
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> 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. > We are interested in the quorum sensing system of Vibrio cholerae, the bacterium understood to be responsible for the deadly diarrhoeal disease, cholera. Cholera 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. >
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> Quorum Sensing in Vibrio cholerae >
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> Most cholera 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. > Our idea is to synthesise Escherichia coli bacteria that will use this ingenious mechanism to communicate with Vibrio cholerae. Our engineered Escherichia coli 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 Vibrio cholerae cells which then become avirulent and harmlessly pass out of the body. >
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> Our Plan >
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> 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 LuxR 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 Escherichia coli 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. > The computational side of the team are focusing on generating ordinary differential equations to model quorum sensing in Vibrio cholerae and on modelling more complex problems such as bistability and multiple quorum loops working in tandem of our parts. >
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Who we are

We are the first University of St Andrews team to enter the iGEM Competition.

We stem from a range of scientific disciplines and our team consists of:

9 undergraduates
2 postgraduates
3 members of staff

The University of St Andrews – Scotland’s First University<b>
St Andrews, founded in 1413 is the oldest university in Scotland and the third oldest in the English-speaking world.

The <a href="http//www.st-andrews.ac.uk/">University of St Andrews</a> is named as one of the top 3 universities in the UK in the <a href="http://www.guardian.co.uk/education/table/2009/may/12/university-league-table>Guardian 2010 league table</a> and is listed in the top 5 of the <a href="http://extras.thetimes.co.uk/gooduniversityguide/institutions/">Times 2010 league table</a> - achieving the highest ever rank of a Scottish university.
<a href="http://www.st-andrews.ac.uk/">http://www.st-andrews.ac.uk/</a>
<a href="http://www.guardian.co.uk/">http://www.guardian.co.uk/</a>
<a href="http://www.timesonline.co.uk">www.timesonline.co.uk</a> </div>

What is the iGEM Competition about?

iGEM (International Genetically Engineered Machine) is the premiere Synthetic Biology competition organized by Massachusetts Institute of Technology (MIT), it is aimed at undergraduates from leading institutions across the globe.

The competition began in 2003 with just 5 teams, by 2009 there were 112 teams and for 2010, 180 teams are predicted to take part.


How does it work?

“Student teams are given a kit of biological parts at the beginning of the summer from the Registry of Standard Biological Parts. Working at their own schools over the summer, they use these parts and new parts of their own design to build biological systems and operate them in living cells.”

“Participants will all specify, design, build, and test simple biological systems made from standard, interchangeable biological parts.”

iGEM Official Website

What is Synthetic Biology?

“An emerging scientific community that is defining a new cross-disciplinary field called Synthetic Biology. Synthetic Biology is fundamentally about the union of Biology and Engineering. iGEM will introduce you to the fundamental ideas of Synthetic Biology and will give you the opportunity to perform cutting edge research in a field that is continually evolving.” - iGEM Official Website



iGEM Official Website </div>

What are BioBricks?

“BioBrick standard biological parts are DNA sequences of defined structure and function; they share a common interface and are designed to be composed and incorporated into living cells such as E. coli to construct new biological systems.

BioBrick parts represent an effort to introduce the engineering principles of abstraction and standardization into synthetic biology. The trademarked words BioBrick and BioBricks are correctly used as adjectives (not nouns) and refer to a specific "brand" of open source genetic parts as defined via an open technical standards setting process that is led by the BioBricks Foundation.”

Wikipedia

<a href="http://en.wikipedia.org/wiki/BioBrick">http://en.wikipedia.org/wiki/BioBrick</a>


What is the Registry of Standard Biological Parts?

“The Registry is a continuously growing collection of genetic parts that can be mixed and matched to build synthetic biology devices and systems. Founded in 2003 at MIT, the Registry is part of the Synthetic Biology community's efforts to make biology easier to engineer. It provides a resource of available genetic parts to iGEM teams and academic labs”

iGEM Official Website

> http://partsregistry.org/Main_Page


<a href="http://partsregistry.org/Main_Page">http://partsregistry.org/Main_Page</a>

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