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Link between inflammation blood clots and the perturbed vessel wall


   School of Medicine, Medical Sciences & Nutrition

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  Prof Nicola Mutch, Dr Claire Whyte  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

This project is one of 17 four year PhD Studentships funded by Medical Research Scotland (https://www.medicalresearchscotland.org.uk) to be delivered jointly by the named University and External Partner Organisation (EPO). The Studentship will provide the first-class academic and additional training provided by the EPO needed to equip the successful candidate for a science career in an increasingly competitive market.

"The role of vascular endothelial cells in dictating local fibrinolytic potential and thromboinflammatory complications" to be delivered by the University of Aberdeen [Supervisors: Professor Nicola J Mutch and Dr Claire S Whyte (both School of Medicine, Medical Sciences and Nutrition, University of Aberdeen) and Synapse Research Institute (https://synapseresearchinstitute.com/) [External Partner Organisation supervisor: Dr Bas de Laat].

Thrombosis is not equivalent in different locations in the vasculature, most likely reflecting changes in shear dynamics, oxygen status and the influence of the local vascular endothelium. The fibrinolytic system is natures ‘own’ clot busting mechanism to resolve haemostatic blood clots and is a crucial step in permitting vessel patency following vascular injury. The central enzyme, plasmin, is formed from cleavage of inactive plasminogen, through the action of tissue plasminogen activator (tPA) and urokinase (uPA). The system is regulated by plasminogen activator inhibitor-1 (PAI-1), which inhibits tPA and uPA, thereby governing plasmin generation. Plasmin is inhibited by α2antiplasmin ( α2AP) which is crosslinked into the forming clot by the transglutaminase, factor XIIIa.

Vascular endothelial cells bind plasminogen and tPA to their surface and produce many factors that govern the fibrinolytic process, including PAI-1. Increased PAI-1 levels are associated with a myriad of diseases including myocardial infarction, atherosclerosis, metabolic syndrome, lung fibrosis, acute respiratory distress syndrome (ARDS), sepsis and other bacterial and viral infections.

This project will investigate the equilibrium between pro and anti-fibrinolytic factors in the environment of the vascular endothelium and how they shape the fibrinolytic response. The PhD will provide training in various experimental approaches including primary cell culture, molecular biology, proteomics, state of the art microscopy, specialist haemostatic assays and microfluidic modelling of the vasculature. The student will visit the external partner organisation, Synapse research Institute in The Netherlands, the founding centre of the calibrated automated thrombinography assay. While visiting Synapse the student will have the opportunity to learn novel techniques and to understand the process of assay development and standardisation. The student will also be involved with clinical studies to collect plasma from individuals with dysfunctional haemostasis to determine their impact on the vascular endothelial response.

ENQUIRIES:

Enquiries should be sent by email to Professor Nicola J Mutch:

[Email Address Removed]

APPLICATIONS:

Applicants must have obtained, or expect to obtain, a 2.1 or first class UK honours degree, or equivalent for degrees obtained outside the UK, in a relevant subject. A first class undergraduate and an MSc degree are preferred.

Applications are welcome from UK nationals, EU nationals that hold UK settled or pre-settled status, or intenational students but please note, international fees are not covered. International students applying for the Studentship must provide evidence by the date of interview that they are able to finance the fee top-up required to the international fee level.

Applications must be submitted online at https://www.abdn.ac.uk/pgap/login.php

You should apply for the Degree of Doctor of Philosophy in Medical Sciences to ensure your application is passed to the correct team.

Please note, your application may be shared with the funders of this PhD Studentship, Medical Research Scotland and Synapse Research Institute.

Interviews are expected to take place approximately 3 weeks after the closing date for applications. Interviews may be conducted by video conference.

It is anticipated that the PhD Studentship will start 3 October 2022.


Funding Notes

PhD Studentship provides: an annual tax-free stipend of £18,500, increasing to £19,000 over the four years; tuition fees at home rates only; consumables; and generous travel allowance. International fees are not covered. International students applying for the Studentship must provide evidence by the date of interview that they are able to finance the fee top-up required to the international fee level.
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