University of Glasgow – PhD in Chemistry – p53 Degradation as a potential approach to cancer therapy

Start Date: 1 October 2025

This scholarship is offered as part of the James McCune Smith Scholarship and Development programme which provides funding for Black UK Domiciled students. 

p53 is a tumour suppressor that is mutated in >50% of cancers. Restoration of p53 function has been shown to lead to tumour regression. Proteolysis targeting chimeras (PROTACs) are bi-functional small molecules that induce degradation of their protein targets. This project aims to synthesise a PROTAC designed to degrade mutant p53, but leave wild-type (WT) p53 (i.e. from a non-mutated allele) unaffected. By degrading the dominant mutant protein, we propose that the tumour suppressor function of the WT protein will resume. The Y220C p53 mutation is the most common mutation seen outside the DNA-binding surface of p53. The small molecule PhiKan9328 has been identified as binding to only the Y220C mutant, not WT p53, and will be the basis for this project.  

The project is based on organic synthesis, including characterisation of all intermediates using analytical techniques such as small molecule NMR. 

This studentship will be jointly supervised by GlaxoSmithKline, including a placement at GSK, Stevenage.

Leading References: 

1) Wiman, K. G. Oncogene 2010, 29, 4245–4252. 

2) Duffy, M. J.; Synnott, N. C.; McGowan, P. M.; Crown, J.; O’Connor, D.; Gallagher, W. M. Cancer Treatment Rev. 2014, 40, 1153–1160. 

3) Perez, R. E.; Shen, H.; Duan, L.; Kim, R. H.; Kim, T.; Park, N.-H.; Maki, C. G. J. Biol. Chem. 2016, 291, 10131–10147. 

4) Lai, A. C.; Crews, C. M. Nat. Rev. Drug Disc. 2017, 16, 101–114. 

5) Patent W O 2017/143291 A1. 

How to Apply: Please refer to the following website for details on how to apply: https://www.gla.ac.uk/scholarships/mccune-smith/how%20to%20apply/