PhD Studentship: Peptidomimetic Inhibitors of Protein-Protein Interactions – A Sustainable Approach

Transient protein-protein interactions (PPIs) control all cellular processes (e.g. mitosis) (1) relevant to health and disease. Thus, a major problem in life-sciences research is to understand and manipulate PPIs with molecular and temporal resolution. Addressing this challenge will illuminate our understanding of disease development e.g. cell signalling in cancer and provide starting points for drug-discovery. Many PPIs employ peptides for recognition which represent viable and potentially powerful starting templates for designing PPI inhibitors. However, peptides have drawbacks, including conformational flexibility, poor proteolytic stability, and suboptimal cell uptake.(2) Similarly current approaches to peptide synthesis are wasteful and use undesirable solvents and reagents.

Our group has developed a number of enabling methods that include constrained peptides,(3) foldamers,(4) protein or peptide-fragment hybrids,(5) coiled-coils(6) and covalent backbone modification(7). A key next step is to develop sustainable and higher throughput methods to prepare and screen peptidomimetics that exploit these capabilities. In this PhD project the student can explore novel synthetic methods alongside state-of the art design strategies for preparation and screening of peptidomimetics (e.g. solvent free amino acid coupling, N- to C- couplings) applied to focussed PPI modulator projects. Relevant targets include: SUMO, BCL-2 family, and interactions of Aurora A kinase (all oncology). A range of techniques will be employed including: peptide chemistry, biophysics and structural-molecular biology.

You will join a vibrant, diverse and group of researchers to gain skills and knowledge in chemical and structural biology in its broadest sense, and, participate in our wider collaborative research.

How to apply for this project

Applications will be considered on an ongoing basis until suitable candidate(s) have accepted an offer. Applicants should contact Prof Andy Wilson (a.j.wilson.1@bham.ac.uk) for informal inquiries, and before applying (with a CV and cover letter summarising your research interests and previous experience). Formal applications should be made through the University of Birmingham’s online application system.

Entry requirements

The candidate should normally have, or expect to receive, a first or upper second (2.1) class Masters degree (or equivalent). The interdisciplinary nature of this research means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, who are interested in using their skills in addressing biological questions. Please contact Prof Andy Wilson (a.j.wilson.1@bham.ac.uk) for further details about this project. For more information on our groups current research activity see: https://ajwilsonresearch.com/

English language requirements

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent (e.g. TOEFL, PTE etc.). The test must be dated within two years of the start date of the course in order to be valid.

References:

1. J. Holder et al, The EMBO Journal, 2024, 43, 5381-5420.
2. H. Wang et al, Chem. Sci., 2021, 12, 5977-5993.
3. D. Gimenez et al, Chem. Sci., 2024, DOI: 10.1039/D4SC06100D.
4. Z. Hegedus et al, Chem. Sci., 2019, 10, 3956-3962.
5. Z. Hegedüs et al, Chem. Sci., 2021, 12, 2286-2293.
6. J. Fletcher et al, Chem. Sci., 2018, 9, 7656-7665.
7. E. Cawood et al, Chem. Sci., 2024, DOI: 10.1039/D4SC02240H.

Funding Details

Additional Funding Information

We offer a fully-funded programme of integrated research and skills training with cross-disciplinary supervision. This studentship includes stipend and tuition fees paid at the UKRI level. Support for conference attendance and research materials will be available.

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