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Organelle dynamics during endothelial senescence

School of Medicine, Dentistry and Biomedical Sciences | PHD

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Funding
Unfunded
Reference Number
SMED-2201-1080
Application Deadline
None specified
Start Date
None specified

Overview

The ageing process in cells is known as cellular senescence. Most research in cellular senescence has been done using fibroblasts; however, it has been suggested that the senescence programme is cell type specific. Therefore, the senescence field requires further research in different cell types. We are interested in endothelial senescence and the ageing of blood vessels; therefore, this project will characterise in detail, changes in organelles during the senescence process in endothelial cells, including vascular stem cells.

A hallmark of cellular senescence is increase in cell size, which is accompanied with increase in mitochondrial mass. Our pilot data in senescent vascular stem cells highlighted an expansion of the endoplasmic reticulum. Recently, it has been suggested that mitochondria-ER contacts promote cellular senescence. This project will investigate the dynamics of organelle changes in endothelial cells through three aims:

To measure the changes in mitochondria, ER, and lysosomes in human endothelial cells during cellular senescence. We will use immunocytochemistry, flow cytometry, Western blotting, and electron microscopy to quantify organelle content in young vs. senescent cells.

To modulate organelle biogenesis to alter the senescent phenotype. We will knock-down or overexpress factors that control organelle biogenesis such as PGC1a and XBP1 for mitochondria and ER respectively. We will evaluate how organelle biogenesis affects senescent establishment.

To study mitochondria-ER contacts as hubs for cellular stress during senescence. It has been suggested that contact sites between mitochondria and ER are mediated by the mitochondria-associated membrane (MAM) which serves as site for assembly of the inflammasome. Here, we will use confocal microscopy, electron microscopy, and protein analysis to study the ER-mitochondria interaction during cellular senescence.

Project Summary
Supervisor

Professor Reinhold Medina

Research Profile


Mode of Study

Full-time: 3 years


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