Postgraduate research opportunities

Investigating Extracellular Vesicle release of pro-coagulant biomarkers

Cardiovascular and Metabolic Disease Cell Biology

Number of places

1

Opens

5 March 2020

Duration

36 Months

Eligibility

B.Sc. in a Biological Science at Upper Second Class or above

Project Details

The release of biomarkers into the bloodstream can be indicative of underlying disease, the detection of which is critical to early diagnosis. Release of the high mobility group box 1 (HMGB1) protein is becoming increasingly associated with onset of infection and inflammation [1], with clinical studies highlighting its detection as a potential diagnostic and prognostic marker of sepsis and cardiovascular dysfunction [2].  HMGB1 is typically recognised as a small protein (<30 kDa) which can be modified by cellular process (oxidation) or cleaved by enzymes to produce a smaller protein during disease (detected in sepsis). One pro-inflammatory enzyme recognised as a regulator of both HMGB1 in sepsis and cardiovascular function is thrombin [3].

In this project, it is proposed that thrombin-dependent release of HMGB1 occurs through cellular bodies called extracellular vesicles (EVs), which then contribute towards cardiovascular disorder of the blood (thrombosis).  Platelets are integral to the blood clotting process in thrombosis and serve as a rich source of both thrombin and HMGB1. Here we aim to investigate the HMGB1 release in platelets through EVs and the role they play in vascular cell inflammation.

Funding Details

Applicant will need to self-fund, find sponsorship for tuition and bench fees of £12000 per annum for duration of studies

Further information

 

Kang, R., et al., (2014). HMGB1 in health and disease. Molecular aspects of medicine. 40: p. 1-116. doi: 10.1016/j.mam.2014.05.001

Wu H, et al (2018): Emerging Role of High Mobility Group Box-1 in Thrombosis-Related Diseases. Cell Physiol Biochem;47:1319-1337. doi: 10.1159/000490818

Ito, T., et al., (2008). Proteolytic Cleavage of High Mobility Group Box 1 Protein by Thrombin– Thrombomodulin Complexes. Arteriosclerosis, Thrombosis, and Vascular Biology. 28(10): p. 1825-1830. https://doi.org/10.1161/ATVBAHA.107.150631