PhD Studentship – Synthesis and Evaluation of Targeted Covalent Enzyme Inhibitors in Cancer

Application Deadline: 10th of June 2019. Interviews will be held from 11th of June onwards. Applications will be considered in the order that they are received, and the position closed when a suitable candidate has been identified.

A fully-funded PhD position is available to start in October 2019 for an outstanding candidate to work under the supervision of Dr Matthias Baud in the School of Chemistry at the University of Southampton. This project will be at the interface of the chemical and biological sciences, and will focus on the development of new types of mild covalent agents as inhibitors or a range of high-profile disease driving proteins. Targeted covalent Inhibitors (TCIs) are protein ligands containing a reactive chemical “warhead” able to create a covalent bond with the protein target. Targeted covalent inhibition of key disease associated proteins is a rapidly growing area of drug discovery. It is a powerful way to increase the potency and/or selectivity of small molecule inhibitors by allowing the covalent, irreversible association of a reactive warhead to specific sites of proteins. Relevant illustrative literature on TCI can be found below:

Chem. Soc. Rev. 2018, 47, 3816
J. Chem. Inf. Mod. 2017, 57, 3124;

The successful candidate will focus on the design and synthesis of TCIs functionalised with new types of mild reactive warheads currently under investigation in our laboratory, along with the evaluation of their bioactivity using in-house in vitro assays. We are particularly interested in the application of these methodologies for 1) improving the selectivity profile of inhibitors across structurally related proteins, 2) along with addressing the challenging issues of drug resistance originating from mutations in cancer. The successful candidate will join the Baud group in the modern synthetic chemistry laboratories in the School of Chemistry at the University of Southampton, which benefits from excellent MS, NMR and X-ray facilities, each supported by dedicated specialist staff. Excellent knowledge and experimental skills in synthetic organic chemistry will be essential, as this will constitute a key part of the project. The multidisciplinary nature of this project will also give the opportunity to the student to acquire knowledge and skills in other relevant disciplines, notably biochemistry and cell biology with our collaborators from Southampton Medicine. Those include a focused range of biochemical and biophysical techniques to evaluate the bioactivity of the new compounds, along with structural characterisation (e.g. computational modelling, X-ray crystallography). The candidate will also have opportunities to develop supervisory, written and oral communication skills, excellent preparation for a career in academia or industry.

The project is funded for 3 years and welcomes applicants from the UK and EU who have or expect to obtain at least an upper second class degree in organic chemistry or allied subjects/relevant disciplines. Funding will cover fees and a stipend at current research council rates of £ 14,296 per annum.

Due to funding restrictions this position is only open to UK/EU applicants

Applications for an MPhil/PhD in Chemistry should be submitted online at https://studentrecords.soton.ac.uk/BNNRPROD/bzsksrch.P_Login?pos=4990&majr=4990&term=201617#_ga=1.23945465.2120898106.1412059827

General enquiries should be made to [Email Address Removed]. Any queries on the application process should be made to [Email Address Removed]

Applications will be considered in the order that they are received, and the position will be considered filled when a suitable candidate has been identified