Investigating the platelet GPIb receptor as a nexus of molecular interactions in inflammation and innate immunity at University of Nottingham on FindAPhD.com

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Dr J Emsley No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

The glycoprotein (GP)Ib-IX complex is expressed exclusively on platelets and is the second most abundant receptor in the platelet membrane. Although GPIb primarily functions as a platelet receptor for von Willebrand factor (VWF), it can also act as receptor for other diverse ligands including thrombin, coagulation factor XI (FXI), factor XII, high-molecular-weight kininogen (HK) and cell receptors P-selectin, integrin αMβ2. The multiplicity of interactions has given rise to the concept that it can serve as a focal point or nexus for platelet function connecting multiple pathways as diverse as hemostasis and immune function.

For more information on this MRC IMPACT Doctoral Training Partnership, please see: http://www.birmingham.ac.uk/schools/mds-graduate-school/scholarships/mrc-impact/index.aspx

There is a growing interest in targeting the GPIb receptor as in animal models where it has shown the potential of reducing thrombus formation without compromising haemostasis, considered the holy grail of antithrombotic therapy, and provides a framework to treat diseases such as stroke. Here you will aim to advance the study of GPIb in the context of interactions with pro-inflammatory mediator HK. In this project you will use the complementary techniques of X-ray crystalllography (UoN), NMR and ITC (UoN) to study the GPIb-HK complex in vitro, together with cell based studies using super resolution light microscopy (UoB) to leverage greater understanding of GPIb. http://www.nottingham.ac.uk/research/groups/structural-biology/index.aspx

Funding Notes

• British nationals who have lived in the UK all their lives are eligible.
• Also eligible are non-British nationals who have settled status AND have been resident in the UK for 3 years immediately prior to the date of the start of the course.
• EU nationals who have been ordinarily resident in the UK and Islands for three years immediately prior to the date of start of the course are eligible.
• EEA and Swiss nationals (EEA migrant workers) should refer to the full RCUK guidelines to check eligibility: http://www.mrc.ac.uk/skills-careers/studentships/studentship-guidance/student-eligibility-requirements/

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Investigating the platelet GPIb receptor as a nexus of molecular interactions in inflammation and innate immunity

University of Nottingham School of Pharmacy