Platelets play a critical role in prevention of excessive bleeding at sites of vessel damage. A critical step in the formation of the haemostatic plug is the release of fibrinogen from platelet α-granules and the subsequent formation of fibrin, which together support platelet clumping and strengthens the clot. Megakaryocytes, the platelet mother cells, produce only small amounts of fibrinogen and as platelets do not have a nucleus fibrinogen must be taken up from the blood and transported to platelet α-granules. This project will investigate the mechanism of uptake of fibrinogen into primary megakaryocytes using a new form of microscopy called lattice light sheet microscopy that enables dynamic monitoring of movement of proteins in a cell for in 3D for extended periods of time. In addition we will use CRISPR technology to genetically delete proteins involved in the trafficking of fibrinogen and test the hypothesis that fibrinogen is taken by the integrin receptor αIIbβ3 into a series of endocytic vesicles and that this process is defective in patients with platelet secretory granule disorders.
The project will be supervised by Steve Watson and Steve Thomas with day-to-day support from microscope and image analysis officers. For informal enquires please e-mail [email protected]
The project will not be able to cover fees for applicants outside of the EU.