relationship with disease and application to personalised medicine.
Supervisor: Dr Mark Wass
School of Biosciences, University of Kent
Genome sequencing projects such as the 1000 genomes project have generated extension
genetic data from which much knowledge about the genetic variation in individuals has been
obtained. However to date the identified genetic variation has only be able to explain a small
proportion of the relationship between genotype and phenotype. So it is now important that we
identify which variants have functional roles, particularly those that have a role in disease.
This PhD project will combine structural bioinformatics and systems biology approaches to analyse
genetic variation and to also develop methods to predict the functional effect of genetic variants.
Particular focus will be on the analysis and use of protein complexes to identify the functional
effects of genetic variants. This will build upon recent analysis demonstrating that diseaseassociated
variants are enriched at protein-protein interfaces (David et al. 2012). The novel
methods developed will be applied to extend our understanding of genetic variation that is related
to disease and will investigate the potential for application to personalised medicine.
Ideally candidates will have some experience of computer programming and an interest in
biochemistry/structural biology and would be particularly suited to individuals with an MSc in
bioinformatics/systems biology.
All candidates are expected to have a minimum of an upper 2nd class degree in an appropriate
field. To qualify for full funding students must be UK or EU citizens. Fuding includes a Stipend paid
at RCUK (Research Council UK) standard rate.
Informal enquiries can be made to Mark Wass mnwass@cnio.es. Full details of the position and
how to apply can be found at: http://www.findaphd.com/search/ProjectDetails.aspx?PJID=39274
Listed below are recent publications by the supervisor Mark Wass that are relevant to the
proposed project:
• David, A., Razali, R., Wass, M.N., Sternberg, M.J. (2012) Protein-protein interaction sites are
hot spots for disease-associated non-synonymous SNPs. Human mutation, 33, 359–363.
• Wass, M.N., Kelley, L.A. and Sternberg, M.J. (2010). 3DLigandSite: Predicting ligand binding
sites using similar structures. Nucleic Acids Res. 38:W469–73.
• Chambers, J.C., Zhang, W., Sehmi, J., Li, X., Wass M.N. et al., (2011) Genome-wide
association study identifies loci influencing concentrations of liver enzymes in plasma. Nat
Genet 43:1131–1138.
• Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass
M.N., et al., (2010) Genetic loci influencing kidney function and chronic kidney disease. Nat
Genet, 42, 373-5.
• Chambers, J.C., Zhang, W., Li, Y., Sehmi, J., Wass, M.N. et al., (2009) Genome-wide
association study identifies variants in TMPRSS6 associated with hemoglobin levels. Nat
Genet, 41, 1170-2.
