How to keep platelets under control and prevent inappropriate activation in disease

Characterisation of RASA3 interaction with integrin and cytoskeletal proteins in platelets

Platelets are a type of cell in our blood that are very important for stopping bleeding after an injury. Damage to blood vessels triggers a rapid series of signalling events which activates platelets, causing them to stick together and form a blood clot. Inappropriate activation of platelets can occur in heart and circulatory diseases where the blood vessels are clogged up with fatty deposits. Harmful blood clots can form and travel to the heart or brain causing a heart attack or stroke. Anti-platelet drugs are effective at breaking up and preventing formation of harmful clots, but they are unsuitable for some people because they can lead to excessive bleeding. In the absence of blood vessel damage, platelets are kept in an inactivated ‘resting’ state. A protein called RASA3 is known to be important for keeping platelets at rest, but how it does this is not known. Dr Kalwant Authi, an expert on platelet biology at King’s College London, has identified a group of proteins that RASA3 interacts with, which are also involved in controlling platelet behaviour. In this project, Dr Authi and colleagues will study cells and platelets isolated from human blood to investigate in detail how these proteins interact. The researchers aim to find out how the interactions differ in resting and activated platelets. This research could lead to new therapies that allow bleeding to be stopped at the same time as preventing inappropriate platelet activation.