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Using computational biology to understand how cancer-associated mutations disrupt protein complexes

  • Full or part time
  • Application Deadline
    Friday, April 03, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

About This PhD Project

Project Description

Applications are invited from outstanding candidates to join the MRC Human Genetics Unit (HGU), part of the Institute of Genetics and Molecular Medicine (IGMM) at the University of Edinburgh. Candidates should hold at least an upper second-class degree in a relevant subject and comply with English language requirements (see application page).

Protein complex assembly is often dysregulated in cancer due to mutations that directly affect protein sequence or cause stoichiometric imbalances. This project will combine genomic and proteomic datasets with a variety of computational approaches, including structural bioinformatics, molecular modelling and machine learning, to systematically study the ways in which cancer-associated mutations affect protein complexes, and compare them to the genetic variation observed in humans and across evolution. The ultimate goal is to identify features of proteins and complexes that explain the phenotypic effects of mutations, and can be used to computationally predict cancer driver mutations from high-throughput sequencing data.

This project will build on the considerable expertise of the Marsh lab at the MRC Human Genetics Unit in studying protein structure, interactions, and disease mutations. Specifically, the goal is to apply methods we have use for studying human genetic disease and protein evolution to cancer. This will be a purely computational project, so ideally, we are seeking candidates who already have bioinformatics experience and are proficient in at least one programming language (e.g. Python). However, candidates from other, non-biological backgrounds with strong computational experience are encouraged to apply.

Please contact Dr Joe Marsh () if you have any questions about the project, or would like to discuss it more detail. Furthermore, there is also considerable flexibility in the precise choice of research topic, as long as it aligns with the general research interests of the Marsh lab.

For details on how to apply, please visit:https://www.ed.ac.uk/mrc-human-genetics-unit/graduate-research-and-training/additional-phd-opportunities

References

Bergendahl LT, Gerasimavicius L, Miles J, Macdonald L, Wells JN, Welburn JPI & Marsh JA (2019) The role of protein complexes in human genetic disease. Protein Science 28:1400-1411

Abrusán G & Marsh JA (2019) Ligand binding site structure shapes allosteric signal transduction and the evolution of allostery in protein complexes. Molecular Biology & Evolution 36:1711-1727

Williamson KA, Hall HN, et al (2019) Recurrent heterozygous PAX6 missense variants cause severe bilateral microphthalmia via predictable effects on DNA-protein interaction. Genetics in Medicine https://doi.org/10.1038/s41436-019-0685-9

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