Finding the mechanisms that control thrombosis

Assembly and function of the engines of coagulation: The prothrombinase and Intrinsic xase complexes

Professor James Huntington at the University of Cambridge is studying new ways to treat thrombosis, where blood clots form when they shouldn’t, which can lead to a heart attack or stroke. Blood needs to clot rapidly to protect us after injury, but blood clots within vessels can also block blood flow. A protein called thrombin is important in the formation of a blood clot and understanding how it is formed could help treat thrombosis. Two groups of proteins must assemble for thrombin to form in high enough amounts to cause the blood to clot – these are called Xase (tenase) and prothrombinase. These protein structures are the ‘engines’ of blood clotting, and are essential for both normal blood clotting and thrombosis. In this project, Professor Huntington will use innovative new approaches to work out how these two protein structure ‘engines’ assemble and function. Although the protein structures are too small to see by the naked eye, he will look at their arrangement at the molecular level using X-ray crystallography and electron microscopy. By giving us crucial insight into how these enzymes control thrombin formation, how thrombin is generated and what goes wrong in thrombosis, this research could help to design new, safe and effective anti-clotting drugs to treat conditions such as heart attack and strokes.