St Georges University of London
The importance of receptor signalling crosstalk in platelets
This is a 3-year funded PhD studentship on GPIb/GPVI signalling supervised by Professor Greenwood and Dr Salles-Crawley at St George’s University of London.
Platelets are anucleate blood cells that play an essential role in haemostasis (blood clotting). Whereas normal platelet function prevents us from bleeding in response to vascular injury, excessive platelet activation and blood clotting can cause myocardial infarction, stroke or deep vein thrombosis. Antiplatelet agents are widely used to diminish the incidence of these thrombotic disorders. Glycoprotein (GP) Ibα and GPVI are two of the major platelet receptors and are crucial to platelet function. Both receptors specifically interact with their respective ligands (von Willebrand Factor and collagen/fibrin) at sites of blood vessel damage. They also transduce cellular signals via tyrosine phosphorylation-dependent pathways leading to the activation of αIIbβ3 integrin that plays a crucial role in platelet aggregate formation. Although these receptors have different ligands, intriguingly, we recently uncovered a role for the intracellular domain of GPIbα in GPVI-mediated signalling events. This project aims to characterise the molecular mechanisms that underpin the cross-talk between these two platelet receptors. Our understanding of these processes will not only elucidate the mechanisms of platelet activation but may also provide new therapeutic opportunities for the prevention of cardiovascular disease.
We hypothesize that the intracellular tail of GPIbα specifically recruits signalling molecules involved in GPVI-mediated signal transduction in platelets.
The project involves 3 main aims:
1) Identify the signalling molecules that associate with the tail of GPIbα that are required for GPVI activation in platelets
2) Characterise GPVI-mediated signalling in GpIbαDsig/Dsig platelets that have a truncated GPIbα lacking the last 24 amino acids of the intracellular tail
Evaluate the importance of VWF-GPIbα signalling in thrombosis and haemostasis
Enquires can be email to Dr Salles-Crawley (email@example.com).
The closing date for applications is Friday 28th January 2022 – please click the following link for further details
To apply for this job please visit www.sgul.ac.uk.