Understanding how blood vessel cells control blood clotting

The role of Ca2+ signalling in the regulation of Weibel Palade Body trafficking and cargo secretion (Miss Katarina Miteva)

The formation of blood clots after damage to blood vessels is essential to prevent excessive bleeding. The first step in this process is the formation of a ‘plug’ of small blood cells called platelets. This is helped along by the release of a substance called von Willebrand Factor (vWF), which is stored in special ‘sacs’ in blood vessel cells called Weibel Palade Bodies. A deficiency in vWF causes several diseases where there is either too little clotting (forms of haemophilia) or irregular clotting, whereas too much vWF circulating in the blood can increase the risk of dangerous clotting and contributes to both heart disease and cancer. Research has shown that several different substances cause the release of vWF from Weibel Palade Bodies by raising the level of calcium in cells that line blood vessels (endothelial cells). But in order to activate an appropriate clotting response, endothelial cells must be able to control this release. This studentship, supervised by Dr Lynn McKeown, will use super-resolution live cell imaging alongside measurements of calcium inside the cell to study this process. Their goal is to decipher the signals that endothelial cells use to govern the precise release of the right amount of clotting factor to halt blood flow.