Investigating the role of cellular senescence in human age-related phenotypes using promoter capture Hi-C
Description: Ageing is highly detrimental to human health. It results in increased severity of infectious diseases and is the primary risk factor for many major non- communicable diseases. One hallmark of ageing is cellular senescence, which is a tumour-suppressing mechanism characterised by irreversible cell cycle arrest. Replicative senescence is a type of cellular senescence. Senescent cells are linked to deleterious consequences when they accumulate and become chronically present in aged organisms. For example, many secrete inflammatory factors, which is thought to contribute to “inflammaging” – a hallmark of immunosenescence. However, the involvement of cellular senescence in many human health conditions is largely unknown. We aim to determine which age- related diseases/phenotypes involve replicative senescence and how genetic variants change the senescence phenotype. We will use promoter-capture Hi-C to determine the promoter-enhancer interactions that change when cells senesce. Results will be integrated with disease/phenotype data from genome-wide association studies. We aim to determine the enrichment of risk-conferring variants in genomic regions of senescence-specific interactions, which will lead to isolation of variants involved in both senescence and disease. We will then explore these variants using CRISPR. This research will increase our knowledge of the fundamentals of ageing and highlight directions for applications of ageing therapeutics.
Funder: Wellcome Trust
Amount:
Funding type: fellowship
Funder scheme: PhD Studentship (Basic)
Start date: 2022-10-01
End date: 2026-01-31
Investigator: Mr Samuel John Catchpole Crofts (lead)
Institution: University of Edinburgh
Subfield: Cell Biology
Domain: Life Sciences
Funded outputs count: 4
Funder award ID: 226831/Z/22/Z
OpenAlex ID: G7214934189