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About the Project
This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP).
The SWBio DTP is funded by BBSRC and involves a partnership of world-renowned universities, research institutes and industry, based mainly across the South West and Wales. This partnership has established international, national and regional scientific networks, and widely recognised research excellence and facilities.
Studentships are available for entry in September 2026.
First stage interviews will be held during the week commencing August 10th.
All SWBio DTP projects will follow a structured training programme to ensure you are well equipped as a bioscience researcher, supporting careers into academia, industry and beyond.
Supervisory Team:
Lead supervisor: Dr Julien Licchesi (University of Bath)
Co-supervisors: Professor Matthew Crump (University of Bristol), Professor Christiane Berger-Schaffitzel (University of Bristol), Dr Scott Lovell (University of Bath)
The Project:
Targeted Protein Degradation (TPD) is transforming modern drug discovery by enabling the selective removal of disease-causing proteins rather than merely inhibiting them. Among TPD strategies, PROteolysis TArgeting Chimeras (PROTACs) have shown remarkable clinical success, particularly in prostate and breast cancers. These bifunctional molecules recruit an E3 ubiquitin ligase to a target protein, triggering ubiquitin-dependent proteasomal degradation. Despite this progress, only a small fraction of the ~600 human E3 ligases are currently used in PROTAC design. Expanding the repertoire of E3 ligases could greatly increase the range of druggable targets and the biological contexts in which PROTACs can be applied. A major challenge, however, is the limited availability of suitable ligands to recruit these underexplored E3 ligases.
Project Aims
This PhD project aims to discover and optimise novel ligands for an underexplored E3 ubiquitin ligase using high-throughput aptamer-SELEX technology. To further broaden the ligand discovery pipeline, complementary screens for affimers, macrocyclic peptides, and covalent ligands will also be undertaken. Ligand binding modes and affinities will be characterised using biophysical and structural biology techniques, including NMR spectroscopy, to guide rational design and optimisation. Promising candidates will be incorporated into next-generation BioPROTAC and PROTAC molecules, which will then be evaluated for target engagement and protein degradation potential in cellular assays using flow cytometry, western blotting, high-content microscopy, HiBiT-NanoLuc, and in vitro biochemical assays.
Training and Methods
This interdisciplinary project provides extensive training in molecular and structural biology, biophysical characterisation, ligand discovery and optimisation, and functional evaluation using cell-based assays. The successful candidate will gain hands-on experience with cutting-edge technologies and benefit from close collaboration with experts in chemical and structural biology, providing a strong foundation for a career in targeted protein degradation research and drug discovery.
Project Keywords: Targeted protein degradation, ubiquitin, chemical biology, PROTAC, Aptamer
Applicant requirements:
We are looking for a self-motivated candidate with genuine passion for scientific discovery. Prior laboratory experience with protein biochemistry, nucleic acid technologies, or biophysical methods would be advantageous.
Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology. Applicants with a Lower Second Class degree will be considered if they also have Master’s degree awarded with Merit.
In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in our projects, a minimum of a grade B in A-level Maths or an equivalent qualification/experience* is required.
* Physics A-level (grade B and above) or units in your degree with a significant mathematical component, e.g. maths, statistics, bioinformatics.
Applicants must ensure they highlight their Maths background within their application and to upload any supporting evidence.
If English is not your first language, you will need to have achieved Academic IELTS 6.5 overall (with no less than 6.5 in any of the four skills). Find details of other acceptable tests and further information on our website.
Enquiries and Applications:
Informal enquiries are welcomed and should be directed to Dr Julien Licchesi: j.licchesi@bath.ac.uk.
Formal applications for this project must be submitted directly to the University of Bath here.
For more information, please see here.
Applications will close on Sunday August 2nd.
