PhD Studentship : Genetic Predisposition to Accelerated Ageing: Targeting Telomeres Using Sex Hormone Supplementation in Chronic Lung Disease

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 58 students over 3 cohorts in its second phase.

Research Theme:  Infection, Immunity, Antimicrobial Resistance & Repair

Summary:  Lung fibrosis is a devastating disease which causes 1% of all UK deaths. On average, patients only survive 2-3 years after diagnosis. Ageing is a big risk factor; patients often have unusually short telomeres (the protective shields at the ends of our chromosomes). This shortening appears to be linked with reduced sex hormone levels in the blood. We will investigate if boosting hormone levels might improve telomere length and reduce disease burden - using data from cutting-edge lab experiments with lung cells, combined with analyses of patient genetics.

Project Description:

Idiopathic pulmonary fibrosis (IPF) is a hugely debilitating disease of ageing, which has a dismal prognosis and a 5-year survival of only 20%. IPF accounts for around 5300 deaths each year (1% of all UK deaths), although this is likely to be an underestimate. Current anti-fibrotic medications are expensive (£27k per patient per annum) and only slow disease progression, while having limited benefit for quality of life - largely due to a range of unpleasant side effects. It is therefore paramount to identify new therapies which are more effective and better tolerated by patients. This proposal represents a novel opportunity to help establish the mechanism and potential efficacy of using sex hormone supplementation as a treatment.

The project will employ a powerful combinatorial approach of genetic analyses, access to patient samples and cutting-edge in vitro approaches. A key hallmark of ageing is the progressive shortening of the telomeres which protect the ends of our chromosomes from becoming damaged. However, the mechanisms are poorly understood by which sex hormones may be able to boost telomere length and thereby reduce the detrimental impact of ageing which underpins disease development. This is a hugely exciting training opportunity in a wide range of cell and molecular biological techniques, genetics and bioinformatics. It has conceptual buy-in from our dedicated patient and public involvement group (PPIEG), and ongoing liaison with our PPIEG will also be an important part of the project. The student would therefore meet with patients, benefit from their insights, and hence co-develop various aspects of the study with a view to delivering the most clinically-meaningful results.

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