PROTACs (proteolysis targeting chimeras) are gaining increasing importance in chemical biology and oncology. They employ hybrid molecules with dual functionalities, one targeting a protein of interest, the other capable of recruiting an E3 ligase that draws in the target protein for ubiquitination and destruction by the proteasome. This new modality effectively repurposes small molecule chemical tools to selectively degrade, rather than simply inhibit, target proteins of interest. A key feature is their catalytic mode of action; PROTACs can repeatedly engage and direct the ubiquitination of target molecules. They can therefore elicit a continued, strong response even at very low, sub-stoichiometric concentrations. Additionally, PROTACs can be used to degrade proteins that although bound, are not effectively inhibited, by small molecules.

The current multidisciplinary project will concentrate on a number of targets of particular current interest. We aim to develop a (drug-like, cell-penetrable, selective, stable) chemical probe to benefit the oncology community.

The student will have a strong background in organic synthesis, preferably with experience of medicinal chemistry, parallel synthesis, automated purification and microwave chemistry. The Spencer laboratory is well equipped with state-of-the-art equipment.

The project will be predominantly chemistry-focussed but the student is expected to spend time in the Morley/Chevassut laboratories gaining experience of cell culture, assays, cancer cell biology.

There will be a 3 months' placement at Tocris' state-of-the-art laboratories in Bristol around the end of year 2, where the student will work on scale up and manufacturing routes to the selected probes from this work. They will also gain experience of marketing in a commercial environment.

The student will be expected to contribute to 50 hours of teaching per year as part of the project and will benefit from substantial training opportunities in Life Sciences at Sussex including health and safety, research ethics, writing publications, reference/citation management software, public engagement, grant bid preparations as well as accessing a wide range of weekly seminars in Chemistry and Biochemistry from world-leading scientists.