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FindA University Ltd Featured PhD Programmes
FindA University Ltd Featured PhD Programmes

Contribution of Trichoplein (TCHP) to impaired proteostasis and vascular senescence in brain vasculature


Project Description

Background

Experimental and clinical studies have suggested that age-related cerebrovascular dysfunction plays a critical role in the pathogenesis of dementia, including Alzheimer’s disease. To date, our knowledge on the contribution of endothelial cell (EC) senescence to cerebrovascular dysfunction is limited. Several mechanisms of cellular senescence could promote endothelial dysfunction, including chronic inflammation, impairment in clearance of misfolded proteins and defective autophagy. We recently demonstrated that the depletion of the binding protein Trichoplein (TCHP) in ECs causes premature cellular senescence. Mechanistically, TCHP is indispensable for autophagosome maturation in ECs, and its depletion resulted in accumulation of unfolded protein aggregates and the transcription of senescent-associated phenotype gene (IL-1b, IL-6 and IL-8). Consistently, accumulation of aggregates was observed in the vasculature of Tchp knock-out mice.

Project

The PhD studentship will characterize the role of TCHP in contributing to impaired proteostasis and vascular senescence in the brain vasculature, therefore contributing to cerebrovascular disease. Through the analysis of Tchp endothelial specific knockout mice, we will aim to identify the mechanisms involved in the accumulation of protein aggregates and determine the impact of proteotoxic stress on endothelial dysfunction in the brain vessels. The project will combine proteomic and transcriptomic approaches and the use of transgenic animals, cell sorting, cell culture and imaging analysis to address the aims.

Research enviroment

The PhD studentship is held by the University/British Heart Foundation Centre for Cardiovascular Science, a world-class research environment at the interface between biological and medical science. The Centre is based in the outstanding facilities of the Queen’s Medical Research Institute at the University of Edinburgh’s Medical Campus at Little France in Edinburgh. The proposed project aligns with the research theme of Vascular Disease and Vascular Dementia in collaboration with Edinburgh Neuroscience and Dementia Research Institute.

Application

We require a one-page personal statement highlighting your motivation for applying to the PhD project; a CV and letters from two academic referees. All documents should be sent or emailed to Lynn Meikle -
Centre for Cardiovascular Science
Queens Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ

Funding Notes

A generous tax-free stipend, research costs and tuition fees (Home/EU) rate are provided Please note that students classified as International for University Fee purposes are not eligible. Please verify your Fee status with the University's Registry before making your application

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