Ubiquitination is a central regulator of the cell and is linked to cancer, neurodegeneration, autoimmunity and infectious disease. Ubiquitination involves the attachment of the small protein ubiquitin to substrates and is carried out by a startling class of enzymes known as E3 ligases (E3s). E3 activity is subject to strict regulation and when awry, leads to diseases such as cancer, neurodegeneration and autoimmunity. The regulatory mechanisms for the ~700 E3s are only known for a handful of members yet exciting and unexpected mechanisms remain to be discovered. This project will use powerful activity-based probe technology to survey E3 activation landscapes in disease-relevant contexts. It will also gain a molecular-level understanding of how E3s associated with disease become activated. This will provide insights into the causes of diseases and how they might be treated. This is a multidisciplinary project and, depending on experience, will combine techniques ranging from cell biology to structural biology.

References:

bioRxiv 2021.05.10.443411; doi: https://doi.org/10.1101/2021.05.10.443411

Life Sci Alliance. 2022, 5:e202101248.

Nature Chemical Biology 2016, 12 (5), 324.

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.