Discovering novel biochemical interactions between the complement and coagulation systems

发现补体和凝血系统之间新的生化相互作用

• 批准号: RGPIN-2017-03810
• 负责人: Conway, Edward
• 金额: $ 3.64万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=710134
• 关键词: Discovering; novel; biochemical; interactions; between

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.

敷设总结 在血液循环中，存在两个高度调节的系统，促进愈合和防止出血。其中之一是所谓的凝血系统，它受到严格控制，以实现出血和凝血之间的关键平衡，并维持血液的流动。另一个是补体系统，用于快速有效地处理入侵的感染并防止组织和器官损伤。从历史上看，这两个系统中的复杂生化途径被视为独立和不相交的。然而，我们和其他科学家小组现在提供的证据表明，它们确实相互作用，这是有道理的，因为这两个系统是由相同的触发器在相同的条件下启动的。此外，参与凝血和补体的许多组分（蛋白质）具有共同的进化起源。因此，这些重要的生物化学途径很可能是协调控制的，并且是高度相互作用的。事实上，我们实验室的大量数据（在过去5年中由NSERC资助发表）支持这样的假设。 我们实验室的长期目标是通过系统地研究凝血和补体系统之间的生化相互作用来创造新的知识，寻求揭示有关不同参与成分的全新信息-它们如何物理相互作用，它们的功能以及生化途径之间的关键联系。为此，我们将利用显微镜的显着进步，使我们能够直接可视化结构和功能的相互作用。我们还将使用先进的生物化学技术，与世界知名的专家合作，在这些方法。 我的实验室有独特的精力来确定血液中这两个最重要系统之间的联系。我们相信，我们将继续提出新颖和重要的意见。 我们的计划是在未来10-15年内扩大这一知识基础，因为我们与学术界和工业界建立伙伴关系，以获得进一步的见解并发现新的途径。这将具有广泛的重要性;例如，它将导致高质量诊断试剂盒的创造性设计，以识别和理解血液中以前未知的蛋白质的功能，创造在药物开发中具有价值的技术，以及提高与血液接触的医疗器械的质量（例如，心脏瓣膜）。这些举措将促进加拿大大学在自然科学和工程方面的卓越研究，刺激高质量的培训，并为加拿大创造新的就业机会，新技术和经济增长。