Development of Reactive Chemistries for Chemical Biology


   School of Chemistry

   Applications accepted all year round  Funded PhD Project (UK Students Only)

About the Project

A key problem in life-sciences research is to understand biomacromolecular function in molecular and temporal resolution – this would provide unprecedented understanding of the molecular mechanisms of health and disease. Moreover using chemical tools to delineate molecular mechanisms has the added advantage of providing tools to manipulate function and starting points for drug-discovery.

Covalent modulators offer several advantages - they can be more potent and selective than reversible modulators,(1) and chemical proteomic methods enable the study of their targets in cells.(2) Photoinduced cross-linking can be used to study target engagement in cells. Both approaches can be used to map the site of interaction between two proteins or a ligand and a protein, to furnish structural information. However, both covalent modulators and photo-crosslinking tools typically inactive a target protein – if these approaches could instead transfer a group to their target, many more possibilities for mechanistic studies of protein function become possible. In this interdisciplinary project, the student will develop state-of-the-art molecular and chemical biology methods for use in chemical and structural proteomics workflows, specifically to identify interacting partners of target proteins.

You will join a vibrant, diverse and group of researchers to gain skills and knowledge in chemical biology in its broadest sense, and, participate in our wider collaborative research. Training will be provided in molecular biology, functional assays, protein labelling,(1, 3, 4) and mass spectrometry-based chemical proteomics.

Applications will be considered on an ongoing basis until suitable candidate(s) have accepted an offer. Applicants should contact Prof Andy Wilson () for informal inquiries, and before applying (with a CV and cover letter summarising your research interests and previous experience). For more information, please see: https://ajwilsonresearch.com/

Funding notes:

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.

References:

1. T. Ueda, T. Tamura, M. Kawano, K. Shiono, F. Hobor, A. J. Wilson and I. Hamachi, J. Am. Chem. Soc., 2021, 143, 4766-4774.

2. F. Meissner, J. Geddes-McAlister, M. Mann and M. Bantscheff, Nature Reviews Drug Discovery, 2022, 21, 637-654.

3. H. A. Beard, J. R. Hauser, M. Walko, R. M. George, A. J. Wilson and R. S. Bon, Commun. Chem., 2019, 2, 133.

4. J. E. Horne, M. Walko, A. N. Calabrese, M. A. Levenstein, D. J. Brockwell, N. Kapur, A. J. Wilson and S. E. Radford, Angew. Chem. Int. Ed., 2018, 57, 16688-16692.

Biological Sciences (4) Chemistry (6)

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