PhD Studentship : Chemical Synthesis and Biological Evaluation of Improved PROTACs Based on a Novel

Dr. Matthias Baud and Professor Bruno Linclau                          

PhD Description: 

Background:

This is an interdisciplinary PhD project suitable for candidates who have a strong interest in both organic synthesis of medicinally relevant compounds and their biological evaluation. The project concerns a novel approach to optimise the activity and physical properties of a relatively new class of bioactive compounds, PROTACs, which are of huge current interest to achieve targeted protein degradation. The organic chemistry aspect consists of the chemical synthesis of a series of fluorinated precursors followed by incorporation into PROTACs, which will be carried out under the supervision of Prof Linclau and Dr Baud respectively. The medicinal chemistry aspect consists of the evaluation of the synthesised PROTACs against a panel of medically relevant proteins while on placement at our industrial collaborator, AstraZeneca. The project originates from the world-leading expertise in organofluorine medicinal chemistry (eg Angew. Chem. Int. Ed. 2012, 51, 6176 (Very Important Paper), Angew. Chem. Int. Ed. 2016, 55, 674 (Very Important Paper)). While synthetic organic chemistry is a key aspect of the project, it contains a strong medicinal chemistry element, and you will become familiar with the significant role of fluorination in current drug optimisation (review: J. Med. Chem. 2015, 58, 8315) and with the burgeoning field of PROTACs (review: Chem. Rev. 2017, 117, 11269). 

Training:

Your studentship will provide training in a range of modern organic synthetic techniques and analytical methods in a world leading interdisciplinary research environment. Apart from synthetic chemistry, you will be trained in carrying out bioactivity assays, and will also develop your knowledge and skills in other relevant disciplines. Those include for example biophysical techniques, biochemistry and cell biology. Finally, you will also have opportunities to develop your supervisory, written and oral communication skills, excellent preparation for a career in academia or industry. Group members are expected to present their work at a range of internal and external (e.g. national and international) meetings and conferences.

The project is funded for 3.5 years, includes a 6-month placement at AstraZeneca in Cambridge, and welcomes motivated applicants from the UK who have or expect to obtain at least an upper second class degree in  Chemistry or allied subjects/relevant disciplines. Funding will cover fees and a stipend at current research council rates (201718 and subject to increase in 201819) of £ 14,553 per annum. Prior experience in synthetic organic chemistry is desirable, as this will constitute a significant part of this project. 

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

General enquiries should be made to m.baud@soton.ac.uk and Bruno.linclau@soton.ac.uk.  Any queries on the application process should be made to pgafnes@soton.ac.uk

Applications will be considered in the order that they are received, and interviews will be organized from the end of February onwards. The positon will be considered filled when a suitable candidate has been identified.