Enhancing the body’s natural anti-clotting system to treat thrombosis

Protein S-TFPI anticoagulant pathway:- molecular mechanisms and therapeutic potential.

Blood clotting is highly coordinated and involves processes that promote clotting and others that inhibit it. One of the body’s natural clot-inhibiting pathways is called the “TFPI-protein S anticoagulant system”. In this system, the TFPI molecule relies on its partner, protein S, but exactly how the two work together is not clear. In this programme grant, Dr James Crawley will develop new tests to study the function of the TFPI/protein S in preventing blood clotting in normal blood flow. First, they aim to work out the physical structure of protein S, by turning it into a crystal and looking at the way X-rays bounce off it. Knowing its structure, they can understand how it changes when protein S attaches to other molecules – which is important for understanding how it works alongside TFPI. With this knowledge they will use antibodies that affect the function of protein S and TFPI and explore the effects in genetically engineered mice. The overall goal is to see whether they can boost the naturally occurring anti-clotting properties of the TFPI-protein S system in mice, which could then pave the way for a new way to treat thrombosis in people.