Targeting molecule scissors to prevent the development of blood clots

Identifying the tetraspanin/ADAM10 ‘molecular scissor’ for the platelet collagen and fibrin receptor GPVI (Miss Chek Ziu Koo)

Platelets are small cells that clump together to plug wounds and minimise blood loss, but when they clump together too much, it can block blood flow and cause heart attacks or strokes. This is called thrombosis. Scientists are studying platelets to see whether their clumping could be blocked, as a potential way to treat thrombosis. In this fellowship, Dr Tomlinson is studying a molecule on the surface of platelets called GPVI, which is a promising drug target for heart attack and stroke. GPVI can be removed from the platelet surface by molecular scissors called ADAM10. Dr Tomlinson’s lab has recently shown that there are six different types of ADAM10, and they each target a different molecule. The main aim of this study is to determine which ADAM10 scissors remove GPVI. They are doing this by using antibodies which can block the function of the different ADAM10 molecules. They will also block another group of molecules called tetraspanins that are needed for ADAM10 molecules to work. This will enable them to stop the cutting action of the different scissors, and work out which combination of ADAM10 and tetraspanin is best to target with anti-clotting drugs.