E3 ligases are a startling class of enzyme that orchestrate the covalent attachment of the small protein ubiquitin to substrates. By doing so they regulate essentially all aspects of cell biology and their dysregulation can also lead to disease onset. E3s were originally thought to transfer ubiquitin solely to lysine residues but it is emerging that non-lysine ubiquitination is also an important cellular process. Our lab has discovered a novel class of threonine E3 ligase, which offers great promise as a therapeutic target for a range of neurodegenerative diseases. We have also identified a class of deubiquitinating enzyme with serine/threonine specificity that are involved in both neurodegeneration and cancer. We aim to further our understanding of the cellular roles of these highly unusual ubiquitin enzymes and the molecular basis of their substrate specificity. This should allow us to assess their biomedical relevance and our ability to develop highly specific drugs that act against them. The lab adopts chemical biology methods but also X-ray crystallography, proteomics and organic chemistry. Inquisitive and technically minded applicants should find the lab a stimulating environment to conduct research.
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Nature Chemical Biology 2020, doi: 10.1038/s41589-020-0598-6
bioRxiv 2020.05.11.087965; doi: https://doi.org/10.1101/2020.05.11.087965
At the MRC PPU, as well as the possibility of a PhD in one particular lab, we offer the possibility of two 4.5-month rotations in labs of their choice. A range of other projects from MRC PPU scientists are advertised on this website. Rotations provide valuable experience and help with deciding on the choice of PhD project and research group.
Please send a CV with contact details of three referees to and a cover letter explaining why you have chosen to apply to MRC PPU to firstname.lastname@example.org. The closing date for applications is 15th December 2020 with shortlisting and interviews in January 2021. Application from overseas students are welcome.