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Modulating endothelial cell crosstalk within tissues to delay and/or reverse ageing

School of Medicine, Dentistry and Biomedical Sciences | PHD

Applications are now CLOSED
Funding
Unfunded
Reference Number
SMED-2211-1186
Application Deadline
None specified
Start Date
None specified

Overview

Blood vessels, running across all tissues, provide a unique biological hub that integrates ageing signals at the molecular, cellular, and organ levels. This project proposes targeting the endothelium as a new strategy to reverse tissue ageing, by modulating ageing-induced altered intercellular communication between endothelial cells and surrounding organ-specific cells.

Altered intercellular communication is a hallmark of ageing, but its manipulation has proven difficult due to its complexity. The vasculature orchestrates cell-cell communication; therefore, we propose that targeting angiocrine signals will facilitate modulation of intercellular communication to potentially reverse ageing. Furthermore, understanding endothelial crosstalk across ageing tissues will enable the smart design and identification of new therapies to delay cellular senescence.

This project has 3 objectives:

To establish a molecular framework for cell-to-cell communication changes during tissue ageing driven by the endothelium. Using bioinformatic tools on scRNA transcriptomic datasets from young and aged tissues, we will characterise cell-to-cell communication changes during ageing, in the brain, lung, heart, and retina.

To model endothelial responses when exposed to aged tissues. Endothelial cells will be co-cultured with tissue explants from young or old animals, to determine paracrine communication from aged tissues to endothelium. Endothelial functionality and signalling will be investigated using 3D angiogenesis assays and protein assessments, respectively.

To modulate endothelial signalling to reverse cell ageing. Pharmacogenomics algorithms applied to results from previous aims will identify drugs that target endothelium with potential to reverse tissue ageing. This will then be tested in vitro using relevant cell coculture models.

Project Summary
Supervisor

Professor Reinhold Medina

Research Profile


Mode of Study

Full-time: 3 Years


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