PhD: Peptides to Boost Brain Cell Recycling in Neurodegeneration

A fully funded four-year GW4 BioMed3 PhD at the University of Bath, designing peptides that switch on TFEB, the master controller of the cell’s recycling machinery, to help neurons clear harmful proteins such as α-synuclein. Open to UK and international applicants. See more funded PhDs.

Neurodegenerative diseases, including Parkinson’s, are linked to a build-up of damaged proteins and faulty cell components. Neurons rely on autophagy to collect unwanted material and on lysosomes to break it down, and a protein called TFEB switches on the genes behind both. Boosting TFEB could help restore waste clearance, but most existing approaches act indirectly, through pathways that control many other cell functions.

This project asks whether short peptides can bind TFEB directly and stabilise the complexes that increase its activity. It is led by Prof Jody Mason at Bath, with Dr Bernadette Carroll and Prof Matt Crump at the University of Bristol.

What you’ll do

The PhD has three linked objectives:

• Find and optimise TFEB-binding peptides. Building on pilot work in the Mason lab, you’ll use computational design (including InsiliCoil) and intracellular peptide library screening, produce recombinant TFEB, and compare linear, cell-penetrating and structurally constrained peptides to see how sequence, shape, stability and cell entry affect activity.
• Work out how the peptides act. Using circular dichroism, fluorescence polarisation and DNA-binding assays, plus NMR and, where appropriate, X-ray crystallography with Prof Crump, you’ll establish how lead peptides bind TFEB and change its assembly and DNA recognition, separating genuine activation from non-specific effects.
• Test recycling and protein clearance in cells. With Dr Carroll, you’ll measure TFEB activity, target gene expression, lysosomal function and autophagic flux in neuronal cell models, and test whether the peptides improve clearance of disease-associated proteins such as α-synuclein.

The first three months are a preparation period for reviewing the literature and pilot data, identifying your training needs and helping shape the plan. After that you can steer the project towards peptide optimisation, structural mechanisms or cellular responses, depending on your interests and the findings.

Who should apply

The project suits applicants from biochemistry, biomedical sciences, neuroscience, molecular biology, pharmacology, chemistry and related subjects. You don’t need previous experience in peptide chemistry or structural biology, as training is provided. You’ll need a first or upper second-class honours degree (or international equivalent) in a relevant area; a lower second will be considered with a Merit or above at master’s level, and significant relevant non-academic experience is taken into account. Non-UK applicants must meet the University of Bath’s English language requirements.

About the programme

The studentship is one of several projects competing for funding from the MRC GW4 BioMed3 Doctoral Landscape Programme, a partnership of the Universities of Bath, Bristol, Cardiff and Exeter. You apply for the project, and the strongest applicants across the partnership are funded. Studentships start in autumn 2027 and run for four years.

Funding

The studentship covers tuition fees and a stipend of £21,805 a year for 2026/27, updated annually, plus up to £5,000 a year for research training and support depending on the project. It is open to UK and international students, though international awards are capped at 30% of the total, and the funding does not cover visa, healthcare surcharge or relocation costs.

How to apply

Apply through the GW4 BioMed3 online application form, which you’ll find with the full project list on the GW4 BioMed website. You can apply for up to two projects in a single application. You don’t need to apply to the University of Bath at this stage; only those offered funding will then apply for a place to study. Applications close at 5pm on Wednesday 21 October 2026, but GW4 may close early for home or international applicants if it receives an unprecedented number, so don’t leave it to the last day. Informal enquiries are welcome, and should go to Prof Mason.