Team:Dundee/Project

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Project

Topic Selection

The team initially held a preliminary meeting to explore ideas that would lead to the decision of a project topic. We broke off into smaller teams to enable discussions to be carried out on areas that may benefit from a synthetic biology solution. From this initial meeting, the team recorded all of the discussed ideas in preparation for a final decision.

The final project goal was decided from the team's second meeting. During our various meetings, the topic of healthcare arose frequently, and was clearly an area of interest to many members of the team. Various healthcare related issues were explored, and the team finally narrowed down the options to tackling C. diff infections in the human gut. The team felt it was feasible to construct a synthetic biological solution that could combat and possibly eradicate C. diff infections.

Project Planning Mindmap

Decision Rationale

The team, originating mainly from Dundee, live within the catchment area of Ninewells Hospital. Ninewells, as well as many hospitals within the country, have faced their own problems with C. diff outbreaks, and the challenges involved in tackling such a problem. Investigation into the area revealed little work by way of a synthetic biology solution, so the team were attracted to the opportunity of developing a synthetic biology foundation to attack the problem.

Furthermore, the number of factors and variables involved within tackling C. diff infection are considerable, ranging from complex cellular interactions to flow factors. This problem lent itself to a wide range of possibilities in terms of mathematical analysis and modelling of the problem area.

Why we chose type VI

At the initial stages of the project it was decided that C. diff would be targeted for eradication from the gut utilising an endolysin specific towards it. The relatively new type VI secretion system was chosen primarily due to its capacity of direct inter-bacterial killing (Cascales & Cambillau. 2012). The remaining types of secretion systems were disregarded for various reasons such as being unable to secrete virulence factors into another organism and instead just releasing them into the environment, as in the case of type II (Sandkvist. 2001) and V (Desvaux et al. 2003). Type III on the other hand, only targets eukaryotic cells (Hueck. 1998), type IV is involved generally in genetic exchange (conjugation) (Desvaux et al. 2003) and type I secretion systems are comprised of 3 proteins (Hueck. 1998) and thus provide a poor cloning challenge. The tip subunits (VgrG and Hcp) of type VI are renowned for their fragility and their ability to be detected in the supernatant, this is also beneficial as it provides an encouraging source of characterisation and may further increase the possibility of endolysin coming into contact with C. diff.