About the Project
A current limitation in the development of novel PROTACs is the ability to directly measure the formation of three-component complexes in a fast and efficient manner. Native mass spectrometry (nMS) is an efficient method for analysing the species present in complex mixtures involving E3 ligases, PROTACs, and substrate proteins. This is due to its ability to report on multiple binding stoichiometries present in dynamic protein mixtures, including species populated to a low extent. When coupled with ion mobility, which is a complementary gas-phase technique, different conformations of proteins or protein complexes can also be separated.
The aim of this PhD project is to further develop native ion mobility mass spectrometry methods for the analysis of PROTACs and other protein degraders, which have strong potential as therapies for cancer and other diseases.
We are looking for a motivated candidate, preferably with experience in protein chemistry and/ or mass spectrometry, to join Dr Rebecca Beveridge and Prof. Glenn Burley in the department of Pure and Applied Chemistry at the University of Strathclyde. To apply please send your C.V., a cover letter and details of two referees to [Email Address Removed]. The cover letter should outline why you’re interested in this project and describe your relevant experience.
Tinworth, Christopher P., et al. "PROTAC-mediated degradation of Bruton’s tyrosine kinase is inhibited by covalent binding." ACS chemical biology 14.3 (2019): 342-347.
Hanzl, Alexander, and Georg E. Winter. "Targeted protein degradation: current and future challenges." Current Opinion in Chemical Biology 56 (2020): 35-41.
Sharon, M. and C.V. Robinson, The Role of Mass Spectrometry in Structure Elucidation of Dynamic Protein Complexes. Annual Review of Biochemistry, 2007. 76(1): p. 167-193.
Roy, M.J., S. Winkler, S.J. Hughes, C. Whitworth, M. Galant, W. Farnaby, K. Rumpel and A. Ciulli, SPR-Measured Dissociation Kinetics of PROTAC Ternary Complexes Influence Target Degradation Rate. ACS Chemical Biology, 2019. 14(3): p. 361-368.
Beveridge, Rebecca, et al. "Mass spectrometry locates local and allosteric conformational changes that occur on cofactor binding." Nature communications 7.1 (2016): 1-9.
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