Understanding and controlling Beta-strand mediated protein-protein interactions using bespoke chemical modifications

University of Leeds

Faculty of Biological Sciences

Project Description

Chemical probes are advantageous in studying the molecular mechanisms of health and disease; they uniquely allow temporary and titratable modulation of a target protein’s function, permitting evaluation of its functional role. Furthermore chemical probes represent starting points for drug-discovery.

This PhD studentship will exploit peptidomimetic design to develop chemical probes that can inhibit post-translation modification of proteins by small ubiquitin-related modifier (SUMO). SUMOylation regulates multiple cellular processes including transcription, replication, and DNA repair. SUMO interacting motifs (SIMs) play an important role in reading, writing and erasing SUMO. SIMs recognize SUMO through non-covalent interaction in a β-strand conformation and are typically found within intrinsically disordered regions of proteins. Here we will apply a state of the art combination of peptidomimetic design and advanced Nuclear Magnetic Resonance (NMR) experiments to identify and characterize chemical probes for a series of SIMS relevant to aggregation and DNA damage.

The student will join a vibrant, diverse and collaborative group of researchers to gain skills and knowledge in peptide and protein chemistry, advanced NMR methods and protein-protein interactions. Ultimately, development of SIM/SUMO chemical probes will contribute to a systematic understanding of intrinsic disorder in β-strand mediated PPIs, and, be crucial in unravelling the “SUMO code”.

Funding Information

This studentship is part of the BBSRC White Rose Doctoral Training Partnership in Mechanistic Biology. (https://www.whiterose-mechanisticbiology-dtp.ac.uk/). Appointed candidates will be fully-funded for 4 years. The funding includes:

Tax-free annual UKRI stipend (£15,609 for 2021/22 starts. Awards increase every year, typically with inflation).

UK tuition fees (Around £4,500 per year)

Research Training and Support Grant (RTSG)

Conference and Professional Internships for PhD Students (PIPS) allowances

We aim to support the most outstanding applicants from inside and outside the UK. We are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.

To apply for this PhD, please email T.Karamanos@leeds.ac.uk.

Before sending your email, please double check you have followed all guidelines in this listing and have included a reference number if asked to do so.