4 Year GTA - Pin-ing it down: Novel Inhibitors for the Enigmatic Pin1 Enzyme to treat Cancer

About the Project

Open to UK applicants only

The School of Chemistry has fully-funded Graduate Teaching Assistant (GTA) studentships available for UK applicants, starting in September 2026.

The opportunities allow successful candidates to pursue their passion for research in the chemical sciences, alongside developing their skills as chemistry lecturers and educators of the future. This includes working toward gaining recognition as an Associate Fellow of the Higher Education Academy.

The GTA involves laboratory demonstrating and other teaching responsibilities in term time, with approximately 80% of your time dedicated to research across the calendar year. These are 4-year positions that include an annual stipend and salary package, full UK tuition fees, and a research and training grant.

Project Highlights

1. Develop drug molecules with a novel mode-of-action
2. Exciting protein target (Pin1) for treating cancer
3. Interdisciplinary training at the chemistry-life science interface

Description

Background: Pin1 is a prolyl isomerase enzyme that catalyses the cis/trans isomerization of proline residues in over 200 protein substrates. Dysregulation of Pin1 levels is strongly associated with regulation of pathways associated with DNA repair and ageing, and is overexpressed in many cancer types. Consequently, the development of strategies to impede and probe Pin1 function has gained significant interest. Despite efforts to design traditional small-molecule inhibitors that target Pin1’s catalytic domain, none have emerged as effective drugs or probes. Thus, there is a need to develop alternative approaches to achieve Pin1 inhibition.

Our team has discovered a new strategy for Pin1 inhibition which involves combinatorial covalent modification of cysteine residues in Pin1 (Figure 1). This leads to the targeted degradation of Pin1 in cancer cells, and impedes cancer cell proliferation. The approach could be a powerful way to induce the degradation of other aberrant proteins across a broad spectrum of disease.

Aim: The aims of this project are to:

(1) understand the molecular mechanisms by which combinatorial covalent modification leads to Pin1 degradation.

(2) exploit this mechanism in the design, synthesis and evaluation of potent and selective Pin1 degraders and inhibitors that are effective against cancer cell lines.

Approach: The project will take an interdisciplinary chemical biology approach drawing on the expertise of the supervisory team. We will use synthetic organic chemistry methods to make new covalent Pin1 ligands alongside a combination of biochemical assays, structural biology, and cellular biology to evaluate their activity and deduce the molecular mechanisms by which they work. In the longer term, we are interested to demonstrate the broad applicability of this approach to other cancer relevant protein targets.

Training: This project will provide excellent training for those with a keen interest in drug design and development, and the chemical events that drive disease progression. You will receive excellent training across the following techniques, providing you with the ideal skillset for future research in the pharmaceutical and chemical biology sectors:

• Organic synthesis and molecular characterisation
• Protein expression and purification
• Protein X-ray crystallography and NMR
• Protein mass spectrometry
• Biophysical assays (e.g.) fluorescence polarisation, isothermal titration calorimetry, and thermal stability assays.

References: 10.1002/pro.5138; 10.1038/s41598-025-89342-0

Enquiries are welcome. To discuss the project in more detail please email r.g.doveston@le.ac.uk.

To apply please refer to the application advice and use the application link at https://le.ac.uk/study/research-degrees/funded-opportunities/chemistry-gta

Start date 21 September 2026

Funding Notes

GTA Studentships provide funding for 4 years to include:

• Tuition fees at UK rates
• A combined teaching and stipend payment (for 2026/7 this will be £21,805 per year, paid in monthly instalments)
• Research training support grant (RTSG)