Unlocking healthy ageing: harnessing proteostasis pathways to promote extracellular matrix function (TAYLOR_U27DTP)
Background:
Ageing causes increased frailty and higher rates of disease. As societies age, this presents an enormous public health challenge, making understanding the ageing process critically important to develop ways to promote age-related health.
One prominent characteristic of ageing is altered extracellular matrix (ECM) structure and function. Changes in ECM properties have been implicated in age-related conditions including cancer, hypertension and stroke, suggesting that therapies targeting the ECM hold high potential to treat age-associated disease.
Another cause of age-related frailty and disease is a collapse in cellular stress responses, molecular pathways that safeguard cellular health. In fact, recent studies show that driving stress response activation increases longevity and resilience, emphasising their core role in healthy ageing. However, how stress responses may affect ECM ageing remains unexplored.
Our preliminary evidence suggests that driving activation of a key stress response in the model organism Caenorhabditis elegans influences expression of ECM components and promotes healthy ageing. This project will test the effects of stress response activation on composition, structure and function of the ECM during ageing, and determine whether these changes drive prolonged health span.
Methodology:
You will utilise transcriptomics and proteomics to determine ECM composition, and advanced imaging techniques including confocal microscopy and transmission electron microscopy to examine ECM structure. You will also use genetic approaches coupled with physiological and survival assays to understand how changes to ECM function influence health span.
Training:
You will gain a wide range of skills in experimental design, bioinformatics, scientific writing and presentation. You will also build expertise in ageing biology, cell biology, ‘omics approaches and genetic techniques. In addition, you will participate in external training courses and conferences, local seminars, research discussion groups and journal clubs.
Person specification:
We are looking for an enthusiastic and highly motivated individual with a strong interest in ageing biology and genetics.