PhD Studentship: The role of microvesicles in vascular inflammation

University of Sheffield - Department of Infection, Immunity and Cardiovascular Disease (IICD), The Medical School

Chronic inflammatory diseases such as asthma, rheumatoid arthritis and inflammatory bowel disease affect millions of people worldwide. Although an effective inflammatory response is essential for host defence and repair, inappropriate and sustained inflammation can lead to severe tissue and organ damage. In general, inflammation occurs in the microvasculature where circulating leukocytes roll along the vessel wall before adhering and then migrating into the affected tissue (1, 2). One of the most important leukocytes involved in the inflammatory response is the neutrophil. Once activated, neutrophils can release microvesicles, small (0.1 – 1 µm) membrane-derived sacs that we have found adhere to endothelial cells and increase inflammation (3).

The focus of this project is to investigate how microvesicles adhere to the endothelium and whether this interaction causes an increase in inflammation. You will use intravital microscopy to directly visualise microvesicle interactions with the endothelium, subsequent recruitment of leukocytes to the vessel as well as migration into tissue. Complementary in vitro flow assays will also be used to drill down into the molecular mechanisms involved. These experiments will provide novel, fundamental insights into the mechanism of action of neutrophil-derived microvesicles in enhancing vascular inflammation.

The Faculty of Medicine, Dentistry & Health Doctoral Academy Scholarships cover Home/EU fee and RCUK rate stipend for three years. Overseas students may apply but will need to fund the difference between the Home and Overseas fee from another source.

Proposed start date: October 2017

  1. V. C. Ridger, P. G. Hellewell, K. E. Norman, Am J Pathol 166, 945 (2005).
  2. E. L. Doyle, V.C. Ridger et al., Blood 118, 4265 (2011).
  3. S. Nolan, R. Dixon, K. Norman, P. Hellewell, V. Ridger, Am J Pathol 172, 265 (2008).
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Northern England