About the Project
Molecular function arises from interactions among groups of molecules. As a consequence genetic disease is not usually linked to single genes, rather the same – or phenotypically similar diseases – are related by the groups of molecules contributing to the disease phenotype. This multigenic nature of disease syndromes explains differences in the penetrance of a disorder and why the exact cause of a disease will be context dependent.
In this project we will exploit a systems and evolutionary understanding of biological knowledge to link genes and genome variation to specific human disease focusing on the functional context of variants. Using this computer-based approach, we will leverage published knowledge and understanding of the organization and evolution of our molecular system to predict for a given disease what is the probable set of molecules and interactions involved in the function underpinning the disease, and where disease-causing variation is likely to arise. Our overall aim is to link an individual’s genetic variation to disease potential by studying mutations and their propensity to be tolerated in the context of population variation.
www.manchester.ac.uk/research/david.robertson
www.manchester.ac.uk/research/m.tassabehji/
Funding Notes
This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form, full details on how to apply can be found on our website https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mrc-dtp/.
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
References
Beleza-Meireles A, Hart R, Clayton-Smith J, Oliveira R, Reis CF, Venâncio M, Ramos F, Sá J, Ramos L, Cunha E, Pires LM, Carreira IM, Scholey R, Wright R, Urquhart JE, Briggs TA, Kerr B, Kingston H, Metcalfe K, Donnai D, Newman WG, Saraiva JM, Tassabehji M. Oculo-auriculo-vertebral spectrum: Clinical and molecular analysis of 51 patients. Eur J Med Genet. 2015 Sep;58(9):455-65.
Jamieson DG, Moss A, Kennedy M, Jones S, Nenadic G, Robertson DL, Sidders B (2014) The pain interactome: Connecting pain-specific protein interactions. Pain. pii: S0304-3959(14)00309-1.
Keith B, Robertson DL and Hentges KE (2014) Investigating the role of locus heterogeneity in protein interaction networks. Frontiers in Systems Biology 5:434.
Jiang X, Feyertag F, Meehan CJ, McCormack GP, Travers SA, Craig C, Westby M, Lewis M, and Robertson DL (2015) Characterizing the diverse mutational pathways associated with R5-tropic maraviroc resistance: HIV-1 that uses the drug-bound CCR5 coreceptor. Journal of Virology 89(22):11457-72.
Stoney RA, Ames RM, Nenadic G, Robertson DL, and Schwartz JM (2015) Disentangling the multigenic and pleiotropic nature of molecular function. BMC Systems Biology 9:Suppl 6:S3.