PhD Studentship: Determining the Role of Proteostasis Decline in Age-Associated Extracellular Matrix Dysfunction

University of East Anglia - School of Biological Sciences

Primary supervisor - Dr Rebecca Taylor

Identifying ways to promote healthy ageing has become a major public health priority as global populations age, increasing burdens of age-related disease. Extracellular matrix (ECM) dysfunction is emerging as a critically important aspect of ageing that underlies a range of age-associated diseases, including cancer and cardiovascular conditions. Recent evidence in invertebrate model organisms has also suggested that improved ECM function is a key means by which molecular pathways that extend longevity improve age-related health. These studies have suggested that targeting ECM structure and function is a promising avenue for treating age-associated diseases.

Another key feature of ageing is the functional collapse of cellular stress responses, pathways that ensure the maintenance of proteostasis under stress. In particular, the unfolded protein response (UPR) that acts to maintain proteostasis in the secretory pathway has been found to play a key role in ensuring longevity, and its dysregulation is associated with a wide range of age-associated diseases.

This proposal will, for the first time, make the link between collapse in secretory pathway proteostasis caused by age-associated UPR decline, and age-related failure to effectively maintain a functional ECM. It will use state-of-the-art approaches in two different model systems, the nematode model organism Caenorhabditis elegans and human cell culture, to advance our knowledge in three ways, by:

• Defining the role of UPR activation in ECM collagen expression and secretion in C. elegans, using transcriptomic, proteomic, and high resolution imaging approaches.
• Determining the role of the UPR-ECM interaction in age-related health in C. elegans, using confocal microscopy, electron microscopy, and physiological and survival analysis.
• Establishing whether ECM ageing can be rescued by UPR activation in human cells, using pharmacological UPR manipulation coupled with mass spectrometry, transcriptomics, and cutting edge biophysical approaches.

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

Entry requirements

The standard minimum entry requirement is 2:1 in a degree related to Biological Sciences.

Mode of study

Full-time

Start date

1 October 2026

Funding

This PhD project is in a competition for a Faculty of Science funded studentship. Funding is available to UK applicants and comprises ‘home’ tuition fees and an annual stipend for 3 years.

Closing Date

10/12/2025

To apply for this role, please click on the 'Apply' button above.