Understanding ageing of the endothelium
The investigations are focussed on identifying the biological and molecular changes that occur when endothelial cells undergo senescence (ageing) and the impact on disease such as diabetes, cancer, heart disease and atherosclerosis.
The technologies utilised encompass, gene arrays of aged cells and tissues, molecular dissection of signalling pathways, biochemical analysis of protein structure and functions, in vitro assays of cellular function, state-of-the art imaging of cellular structures and protein localisation, animal models using genetically mutant mice and disease models and zebrafish for vascular analysis.
Our work in the area of endothelial cell ageing has:
1. Identified a novel gene that when overexpressed induces endothelial cell ageing (Coleman et al Blood 2010).
2. Redefined the impact of senescence in the vasculature. The inflammatory phenotype of senescent endothelial cells is unlike other cell types in that they show an anti-inflammatory phenotype. This suggests that senescence plays an unique role- to both inhibit and promote inflammation. The outcome of senescence for the tissue may be time and severity of insult dependent.
Thus, the thrust of our work is now to identify senescent endothelial cells in disease and investigate their impact on disease progression.
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The opportunity ID for this research opportunity is: 70
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