Discovering novel biochemical interactions between the complement and coagulation systems

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Lay Summary Within the circulation, there exist two highly regulated systems that promote healing and prevent bleeding. One of these, the so-called coagulation system, is tightly controlled to achieve a critical balance between bleeding and clotting and to maintain the flow of blood. The other, the complement system, serves to rapidly and effectively dispose of invading infections and to prevent tissue and organ damage. Historically, the complex biochemical pathways featured in these two systems have been viewed as separate and non-intersecting. However, we and others groups of scientists now provide evidence to suggest that they do interact, which makes sense as both systems are initiated by the same triggers, under the same conditions. Moreover, many components (proteins) involved in coagulation and complement share a common evolutionary origin. It is likely, therefore, that these important biochemical pathways are co-ordinately controlled and highly interactive. Indeed, we have considerable data from our lab (published in the last 5 years with NSERC funding) that support such a hypothesis. The long-term goal of our lab is to create new knowledge by systematically examining the biochemical interactions between the coagulation and complement systems, seeking to reveal entirely new information about the different involved components - how they physically interact, their functions and the critical links between the biochemical pathways. To do this, we will take advantage of remarkable advances in microscopes, that allow us to directly visualize the structure and function interactions. We will also use sophisticated biochemical techniques, collaborating with world-renowned experts in these methods. My lab has uniquely devoted energies to identify connections between these two most important systems in the blood. We are confident that we will continue to make novel and important observations. Our plan is to expand this knowledge base in the coming 10-15 years, as we forge partnerships with academia and industry to gain further insights and discover new pathways. This will be of wide importance; for example, it will lead to the creative design of high-quality diagnostic kits to identify and understand the function of previously unknown proteins in the blood, to create technologies that will be of value in drug development, and in improving the quality of medical devices that come in contact with blood (e.g., heart valves). Such initiatives will foster research excellence in the natural sciences and engineering in Canadian universities, stimulate high quality training, and create new jobs, new technologies, and economic growth for Canada.