University of Dundee

Understanding regulation of ubiquitin signalling

University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit, Dundee, United Kingdom

Protein ubiquitylation modifies protein function and regulates almost every process in eukaryotic cells. An indispensable role for ubiquitylation is to serve as a signal for the degradation of misfolded and damaged proteins. In addition to degradation, ubiquitin modifications serve as distinct signals to facilitate intracellular communication. Given these important roles for ubiquitylation, it is important that these signals are regulated. Proteases called Deubiquitinases (DUBs) carry out this important function by erasing or editing ubiquitin signal to regulate the functional outcome of ubiquitylation. Indeed, deregulated DUBs are responsible for several diseases ranging from inflammation and cancer to neurodegeneration. Further DUBs are used by pathogenic bacteria and viruses to establish infection and disease. Hence, there is immense interest in exploiting DUBs as therapeutic targets for which a detailed understanding of the mechanisms underlying DUB activation and substrate targeting is essential.

We are looking for an enthusiastic student to join the group to define how a disease-related DUB regulates cell proliferation and differentiation. You will study how interplay between the different domains of the DUB controls enzyme activity and substrate recognition.  You will use the insights gained from this work to devise strategies to interfere with ubiquitylation of the target substrate and thereby modulate cell proliferation. Your PhD will build upon tools, reagents and models we have recently established in the lab. Working on an independent project, you will have the opportunity to learn and apply different approaches ranging from biochemistry, cell biology, structure biology and state-of-the-art proteomics methods to understand at the molecular level how DUBs regulate ubiquitin signalling.

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 mrcppu-phd-admin@dundee.ac.uk. The closing date for applications is 15th December 2020 with shortlisting and interviews in January 2021. Application from overseas students are welcome.

Eligibility