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Studying the immune systems first responders: neutrophils and platelets. Friends of foes?


Biosciences

Prof Felicity Gavins Applications accepted all year round Self-Funded PhD Students Only

About the Project

Cardiovascular disease (CVD) remains the leading cause of death worldwide particularly in developed countries, with inflammation being central to its pathophysiology. Hence, inflammation is currently considered as a modifiable risk factor for CVD, with neutrophils playing a central role. Neutrophils make up 60-70% of human circulating leukocyte levels (10-25% in mice) and are generated in the bone marrow at a rate of 1011 cells per day. Mechanistically neutrophils have crucial functions in immunity and repair, providing the first line of defence, yet despite their involvement in immunity, neutrophils function as a double edged sword, because they also mediate tissue injury, perpetuate the inflammatory response and contribute to peripheral coagulation and platelet aggregation that accompanies a range of pathological conditions including ischaemia reperfusion injury (often unavoidable sequelae in solid organ transplantation [being linked to graft damage]), sepsis, inflammatory bowel diseases, blood disorders and cancer.1-8 Additionally, neutrophils display diversity in their phenotype in inflammation, although their association with CVD risk and outcome is still mainly unexplored.2,3

Extensive interactions occur between neutrophils and platelets which mediate their ability to regulate haemostasis, inflammation and innate immunity. These first responders of the immune system play crucial roles in maintaining vascular and tissue integrity and their crosstalk is thus a common feature of CVDs and inflammatory immune reactions. Platelet enrichment near the vessel increases neutrophil encounters, which increases the chances of heterotypic interactions, promoting intravascular thrombosis.1,2 We have previously shown that the N-terminal Annexin A1 mimetic peptide Ac2-26 promotes an endogenous biosynthetic circuit in which neutrophil-formyl peptide receptor 2 (Fpr2/ALX) (a key receptor involved in the resolution of inflammation) controls neutrophil platelet aggregate formation by rapid generation of the pro-resolving mediator aspirin triggered lipoxin A4, although the exact mechanism(s) remains unknown.3

This PhD project will build on previous studies to investigate and untangle the mechanism of neutrophil-platelet crosstalk and its consequence on neutrophil phenotype and function with the objective of developing novel drugs for the treatment and prevention of CVDs.

Training/techniques to be provided

The student will be trained in several in vivo skills including animal handling and maintenance, animal anaesthesia and surgical models. The candidate will be trained to use in vivo imaging techniques (e.g. intravital microscopy) and perform a variety of in vitro methodologies which may include histology, immunohistology, electron microscopy, immune cell functional assays (e.g. chemotaxis, transmigration, granule release assays, NETosis), molecular biology, flow cytometry and flow chamber systems. The candidate may also be working with clinical samples. The student will have the opportunity to collaborate and work with a number of groups based both in the UK and globally.

This PhD project will be supervised by Professor Felicity Gavins. If you are interested in applying for this PhD project or if you prefer a one-year MPhil on a similar topic, contact Professor Gavins to discuss your interest and discover whether you would be suitable.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject (e.g. physiology, pharmacology, biomedical sciences). Candidates with experience in in-vivo pharmacology and immune-histochemistry are encouraged to apply. The duration of this PhD project is three years.


Funding Notes

Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: View Website. The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.
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