Investigating how pharmacological modulation of the mTOR-eEF2K/eEF2 signalling axis impacts haemopoietic stem cell function during ageing

Supervisors

Alison Michie, School of Cancer Sciences (University of Glasgow) 

Colin Selman, School of Molecular Biosciences, (University of Glasgow)

Richard Mort, Health and Medicine, (University of Lancaster)

 

Summary

Life expectancy in the UK has increased significantly, with males now living to 78.6 years and females to 82.6 years on average. However, this increase is not matched by similar extensions in healthspan; the period of life free from age-related disease. Understanding the processes underlying ageing and identifying strategies to slow ageing are essential for extending healthy lifespan.  Stem cells play a critical role in maintaining tissue and organ function, with their dysfunction and the loss of regenerative potential identified as a hallmark of ageing. Haemopoietic stem cells (HSCs), which give rise to all blood cells, exhibit age-related changes including reduced self-renewal ability and dysregulated production of mature blood cells (e.g. myeloid skew). These alterations impair immune function, a phenomenon termed immunosenescence, and significantly contribute to morbidity and mortality during ageing.

This project focuses on understanding how ageing affects HSCs and investigates the role of the mTOR-eEF2K/eEF2 pathway as a potential target for pharmacological intervention. By repurposing drugs that act on this pathway, the research aims to modulate HSC function and slow stem cell ageing. The project will assess mechanisms behind HSC self-renewal, lineage differentiation, cell quiescence, and age-related molecular changes using a range of molecular, biochemical and imaging techniques.