Structural Basis of Molecular Recognition in Haemostasis

血液凝固是一个在严格调控下的复杂过程。作为对血管破裂的反应，一连串的事件导致快速和局部的血凝块沉积，从而阻止血液从伤口流出。如果凝血反应不够迅速和有力，就会导致出血，然而，如果凝血不受限制，凝块就会过度生长，导致血栓形成。这种“止血平衡”对人类健康至关重要，了解调节机制对于血栓形成的诊断、预防和治疗至关重要，血栓形成是工业化世界发病率和死亡率的主要原因。这项研究的目的是了解使血液凝固从其不稳定的平衡中导致血友病、深静脉血栓形成、肺栓塞、心脏病发作和中风等疾病的因素。这将通过获得在血液凝固的关键阶段形成的多蛋白复合物的分子图像来实现，主要是通过使用x射线晶体学技术。这些详细的图片将有助于确定为什么某些人更容易患凝血障碍，并将为预防和治疗血栓形成的新疗法的发展奠定基础。

Blood coagulation is a complex process under tight regulatory control. In response to blood vessel rupture, a cascade of events leads to the rapid and localised deposition of a blood clot which staunches the flow of blood from the wound. Bleeding results if the clotting response is insufficiently rapid and robust, however, if coagulation is not limited, the clot will over-grow resulting in thrombosis. This ‘haemostatic balance‘ is critical for human health, and understanding the regulatory mechanisms is crucial for the diagnosis, prevention and treatment of thrombosis, the leading cause of morbidity and mortality in the industrialised world. The goal of this study is to understand the factors which tip blood clotting from its precarious balance to cause diseases such as haemophilia, deep vein thrombosis, pulmonary embolism, heart attack, and stroke. This will be achieved by obtaining molecular pictures of the multi-protein complexes which are formed at critical stages of blood coagulation, primarily by using the technique of X-ray crystallography. Such detailed pictures will help determine why certain people are more susceptible to coagulation disorders, and will underpin the development of novel therapies to prevent and treat thrombosis.