During the 2008/09 academic year I studied for a Systems Biology MSc at University of Warwick. Terms 1 and 2 provided taught courses giving me the knowledge to continue onto a largely biological PhD as well as the tools and ability to apply mathematics learnt at undergraduate level to complex biological problems.

Term 3 and the summer were spent on two miniprojects, one dry and one wet, giving a taste of life in research and providing motivation for PhD work.

Miniproject 1

My first, dry, miniproject was titled "Statistical analysis of Salmonella adaptation" and supervised by Dr Xavier Didelot in the Department of Statistics. The following is the abstract taken from the writeup:

Salmonella are bacteria that causes grave diseases in humans, occasionally resulting in death. It cost the USA an estimated US$3bn in 2008 according to the World Health Organisation. The bacteria may infect both humans and animals. While there is some indication that some samples of Salmonella are more likely to infect humans than non-humans, the extent of this adaptation has never been quantified.

Using Multi-Locus Sequence Typing (MLST), over 2000 isolates have been typed over the last 5 years. This study uses some of this existing data from a variety of serovars to investigate the existence and extent of adaptation in general in Salmonella, ignoring the adaptation between individual serovars already known to exist and looking to show a genetic-level cause for the adaptation events.

A phylogenetic tree, a graphical representation of the evolutionary distance between many sequences, is used to visualise the data allowing inspection for any obvious evidence of adaptation. From here, a trivial model is built with no historical points at which adaptation occurred, allowing comparison with further models allowing the possibility of there having been one or an unknown number of such points, the latter using MCMC methods due to its complexity.

Using MatLab, I created and investigated a phylogenetic tree for Salmonella serovars based on 110 samples from various labs, equally split between those from humans and non-humans. The goal was to see whether adaptation of serovars to different hosts was linked in some way to the evolutionary distances between them.

Differentation of bacteria by serovars is based on proteins in their surfaces, which will play roles in host acceptance since they are the first point of contact between bacterium and host. It therefore makes sense to differentiate in this way, but genetic differences could also be plausible to use. We found no evidence to suggest that this genetic-level differentiation is valid but further analysis on a larger, more relevent dataset may prove otherwise.

Miniproject 2

My second (wet) miniproject was supervised by Dr Miriam Gifford at HRI, titled "How did nodulation evolve in plants: What was the blueprint?". My PhD is a continuation of the work begun in this project. The abstract is as follows:

Fixed nitrogen availability is a key limiting factor on plant growth so nitrogen-poor environments have a big effect on agriculture. Fertilisers are used to provide the necessary nutrients when lacking. Natural, cheaper alternatives are needed in the long run. Legumes obtain their fixed nitrogen using nitrogen fixing bacteria in root nodules, so we ask why can non-legumes not do the same? We analysed existing data and expression data from the lab to identify genes with potential roles in the process in the model legume Medicago truncatula and studied potential orthologs in the non-legumeArabidopsis thaliana to investigate genes implicated to have been co-opted during evolution for the nodulation process from roles in lateral root formation. Gene At5g49960 was identied as being a potential suppressor in Arabidopsis of lateral root formation in high nitrogen conditions.

Using a combination of network & genetic analysis and experiments on nitrogen time courses & knockout lines, we investigated genes implied as having been co-opted for nodulation (CON genes) in the legume Medicago and their orthologs in the non-legume Arabidopsis, examining the levels of nitrogen regulation and identifying a subset of these genes that have clear effects on levels of lateral root formation in Arabidopsis, a process with clear links with the phenomenon of nodulation.