4 Year Wellcome Trust PhD Programme: Investigating the consequences of population variation on the sites of post-translational modifications

Advances in DNA sequencing technology have led to an explosion in available sequence data across many organisms. As a consequence, in human, exome and genome sequencing is now being used routinely to characterise the variability in the human population at the single base resolution in order to aid understanding of disease susceptibility. Large projects in the UK and internationally are in progress to sequence the complete genomes of tens of thousands of individuals with rare diseases and cancer while sequencing of cancer cell lines is revealing the complexity of evolution at the level of individual tumours. Fast, low cost sequencing is also allowing the diversity and progress of infectious diseases to be tracked. Together, these initiatives have led to a large collection of data on genetic variation within species that can be analysed in concert with variation across species to reveal key functionally important sites in the genome.
This computational biology project will build on recent research in the group on the analysis of protein families and protein-protein interactions in context with available data on non-synonymous SNPs[1]. The project will initially focus on analysing the distribution of nsSNPs at a variety of sites of protein post-translational modification in context with available structural and functional data. Key predictions, e.g. the likely importance of a specific site of post-translational modification, may be followed up experimentally through existing collaborations the group has. The project will require the student to develop strong computer programming and data analysis skills, so as well as furthering understanding of basic biology and genetics, the student will obtain excellent transferable skills.

1. MacGowan, S.A., Madeira, F., Britto-Borges, T., Schmittner, M. S., Cole, C., Barton, G. J., Human Missense Variation is Constrained by Domain Structure and Highlights Functional and Pathogenic Residues bioRxiv preprint, 2017. https://doi.org/10.1101/127050