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The application of spatial transcriptomics to the study of accelerated atherosclerosis in human vein grafts


Project Description

There is a unique opportunity to join an established translational research group led by Prof. Gavin Murphy at the BHF-funded Cardiovascular Research Centre in Leicester.

The long saphenous vein (LSV) is the most commonly used conduit in coronary artery bypass graft (CABG) surgery. The LSV however, suffers from the disadvantage of developing late stage vein graft disease (stenosis and occlusion) due to intimal hyperplasia (IH) and accelerated atherosclerosis. Our research group is currently evaluating the cellular and molecular mechanisms underlying these processes using human tissue collected from patients undergoing cardiac surgery.

To date, there is no successful treatment or prevention strategy for vein graft disease, mainly due to the lack of a comprehensive understanding of the disease's molecular background. That includes changes in the different cell layers of veins in response to a new haemodynamic environment after implantation, interactions between cell types, and genetic phenotypes.

The project involves measuring flows, shear stress and wall tension in human vein grafts in situ. These are then reproduced ex-vivo in segments from the vein used to form the bypass graft. Changes in cell phenotype and cell-cell interaction ex vivo will be compared to the development of neointima measured using optical coherence tomography in the vein grafts in patients at 1 year.

The PhD studentship will focus on the interaction between acute changes in shear stress in implanted vein grafts and the subsequent personalised changes in cell signalling in the vessel wall. The successful candidate will investigate molecular mechanisms involved in endothelial-to-mesenchymal transition (EndMT) in vein graft samples from patients undergoing CABG. Expression profiling across three layers of the vein will be performed using cutting-edge spatial sequencing technology. The candidate will also undergo training in MRC key skills including bioinformatics, machine learning, and biostatistics. They will also work as part of an international research group that includes research units in the UK (Oxford and Bristol) and Europe (Milan, Italy).

Entry requirements

Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject. The University of Leicester English language requirements apply where applicable: https://le.ac.uk/study/research-degrees/entry-reqs/eng-lang-reqs

How to apply

Please refer to https://le.ac.uk/study/research-degrees/funded-opportunities/cls-cvs-zakkar-2020 for application advice

Funding Notes

3 year Studentship

Annual stipend at UKRI rates

UK/EU tuition fee waiver

How good is research at University of Leicester in Clinical Medicine?

FTE Category A staff submitted: 72.10

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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