Project description

This project is recruiting to a 1st February 2026 start date.Ageing is associated with increased rates of disease, including neurodegenerative conditions. Prion-like proteins (PrLPs) play major roles in age-associated neurodegeneration, but their physiological functions are often poorly understood. Defining these functions would increase our understanding of the behaviour and importance of PrLPs, and how and why they become dysregulated with age. This is critical to understanding the key roles they play in age-related neurodegeneration.

We recently characterized an unstudied PrLP in C. elegans that scores highly for prion-like amino acid composition. This protein is essential for resistance to stress and pathogens, and localises to lysosomes. As lysosomes play key roles in stress responses and ageing, we want to understand this protein’s functions at the lysosome, to define a novel role for PrLPs in determining stress resistance through effects on lysosome function. This project will comprehensively examine the roles of this novel PrLP by:
1) Defining its roles in lysosome activity, localisation and dynamics
2) Establishing the contribution of its domains to these roles
3) Determining its involvement in pathways that promote healthy ageing

In addition, we will collaborate with the lab of Prof. Tom Wileman to determine the conservation of these mechanisms in mammalian cells. Through these approaches, we will expand our knowledge of the roles and regulation of PrLPs in vivo, providing critical insight into how these proteins become dysregulated with age. We will also increase our understanding of the roles and importance of lysosome regulation in stress resistance and ageing, identifying novel roles played by PrLPs and lysosomes in the ageing process and in anti-ageing interventions. These insights may ultimately lead to the identification of new targets for the development of therapies for ageing and age-related disease.

For more information please contact: rebecca.c.taylor@uea.ac.uk

The Norwich Research Park Biosciences Doctoral Training Programme (NRPDTP) is offering fully funded studentships for October 2026 entry. The programme offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three-month professional internship placement (PIPS) during their study. The placement offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team.

This project has been shortlisted for funding by the NRPDTP.

Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/.

Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background.

To maximise accessibility and attract students from underrepresented groups to our programme we have introduced bespoke templates for applicant Personal and Research statements which will enable every applicant to fully represent themselves through providing suitable examples and evidence. These forms are on the NRPDTP website and must be used for these sections of the application form.

Entry requirements

At least UK equivalence Bachelors (Honours) 2:1. English Language requirement (Faculty of Science equivalent: IELTS 6.5 overall, 6 in each category).

Funding

This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership PhD DTP studentship. The studentship includes payment of tuition fees (directly to the University), a stipend to cover living expenses (2025/6 stipend rate: £20,780), and a Research Training Support Grant of £5,000pa for each year of the studentship.

References

De-Souza, E.A., Thompson, M.A., Taylor, R.C. (2023). Olfactory chemosensation extends lifespan through TGF-β signaling and UPR activation. Nature Aging 3, 938–947

ii)

Özbey, N.P., Imanikia, S., Krueger, C., Hardege, I., Morud Lekholm, J., Sheng, M., Schafer, W.R., Casanueva, M.O., Taylor, R.C. (2020). Tyramine Acts Downstream of Neuronal XBP-1s to Coordinate Inter-Tissue UPR Activation and Behavior in C. elegans. Developmental Cell 55(6): 754-770

iii)

Imanikia, S., Özbey, N.P., Krueger, C., Casanueva, M.O., Taylor, R.C. (2019) Neuronal XBP-1 Activates Intestinal Lysosomes to Improve Proteostasis in C. elegans. Current Biology 29(14): 2322-38

iv)

Heckmann, B.L., Teubner, B.J.W., Boada-Romero, E., Tummers, B., Guy, C., Fitzgerald, P., Mayer, U., Carding, S., Zakharenko, S.S., Wileman, T., Green, D.R. (2020) Noncanonical function of an autophagy protein prevents spontaneous Alzheimer's disease. Science Advances 14;6(33):eabb9036.

Franzmann, T.M., Alberti, S. (2019) Prion-like low-complexity sequences: Key regulators of protein solubility and phase behavior. J Biol Chem 294(18):7128-7136

Exploring the roles of a novel prion-like protein in stress resistance and ageing (TAYLOR_U25DTPR)

Welcome to Norwich

Project description

Entry requirements

Funding

References