Modulation of Smooth Muscle Cell Function by Neutrophil Microvesicles

About the Project

The leading cause of death globally is cardiovascular disease (CVD), according to the World Health Organisation. Atherosclerosis is the underlying cause of most of these deaths. It is a long-term disease of the blood vessels, where fat and inflammation builds up in the walls of arteries to form a plaque that can lead to heart attack and stroke. Smooth muscle cells (SMCs) play a key role in preventing rupture of these plaques. Another cell, the neutrophil, which is the most abundant white blood cell in the circulation, drives atherosclerosis via mechanisms that remain incompletely understood. Neutrophils produce microvesicles, small bags of biological material, and higher levels of these microvesicles have been found in patients with heart disease. We demonstrated that neutrophil microvesicles like to stick to parts of arteries where atherosclerosis happens, and that they can increase the inflammation and fat build-up in these areas.

This studentship will investigate in more detail how neutrophil microvesicles affect the way that smooth muscle cells behave and aims to identify novel ways to reduce heart attacks and stroke, caused by atherosclerosis. Experiments will involve culture of human smooth cells and isolation of human neutrophil microvesicles, confocal microscopy, flow cytometry, RNAseq, bioinformatics, ELISA, and other functional assays. You will determine whether microvesicles interact with SMCs and induce gene expression changes that lead to functional changes in SMCs. This is a unique project that will add to the information we have already gathered regarding the role of neutrophil microvesicles in atherosclerosis that was published in Nature Communications.

Entry Requirements: Candidates must have a first or upper second class honours degree or significant research experience.

How to apply: Please complete a University Postgraduate Research Application form available here: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying. Please clearly state the prospective main supervisor in the respective box and select ‘School of Medicine & Population Health: Infection Immunity & Cardiovascular Disease’ as the department.