Julien Licchesi

This PhD project, offered through the South West Biosciences Doctoral Training Partnership (SWBio DTP) and hosted at the University of Bath, focuses on the rational design of novel degraders for targeted protein degradation. The SWBio DTP is a BBSRC-funded collaboration among leading universities, research institutes, and industry partners across the South West and Wales, providing a rich environment for bioscience research and training. The project is supervised by Dr Julien Licchesi (lead, University of Bath), with co-supervision from Professor Matthew Crump and Professor Christiane Berger-Schaffitzel (University of Bristol), and Dr Scott Lovell (University of Bath). Targeted Protein Degradation (TPD) is a cutting-edge approach in drug discovery, enabling the selective removal of disease-causing proteins. The project will focus on expanding the use of E3 ubiquitin ligases in PROteolysis TArgeting Chimeras (PROTACs), which have shown clinical success in cancer therapy. The main aim is to discover and optimize novel ligands for underexplored E3 ligases using high-throughput aptamer-SELEX technology, as well as complementary screens for affimers, macrocyclic peptides, and covalent ligands. The project will employ advanced biophysical and structural biology techniques, including NMR spectroscopy, to characterize ligand binding and guide rational design. Promising ligands will be incorporated into next-generation BioPROTAC and PROTAC molecules, which will be evaluated in cellular assays using flow cytometry, western blotting, high-content microscopy, HiBiT-NanoLuc, and in vitro biochemical assays. The successful candidate will receive interdisciplinary training in molecular and structural biology, ligand discovery, biophysical characterization, and functional evaluation using cell-based assays. This project is ideal for candidates with a strong interest in chemical biology, protein biochemistry, and drug discovery. Funding is available through the SWBio DTP studentship, covering tuition, a stipend (£20,780 p/a in 2025/6), research and training costs, fieldwork, conference attendance, and a 3-month placement. The studentship is open to both Home and International students, though international funding does not cover visa or healthcare costs, and awards to international students are limited. Applicants should have a strong academic background in a relevant science or technology field, with a minimum of a First or Upper Second Class UK Honours degree (or equivalent), and a solid foundation in mathematics. Prior laboratory experience in protein biochemistry, nucleic acid technologies, or biophysical methods is advantageous. The application deadline is 3 December 2025. For informal enquiries, contact Dr Julien Licchesi at [email protected]. Formal applications must be submitted via the SWBio DTP online application form. The SWBio DTP is committed to supporting students from diverse backgrounds and offers flexibility for those with additional needs.