Structural dynamics and developmental regulation of the editosome complex in trypanosomatids

锥虫是引起人类和牲畜疾病的原生寄生虫。它们是导致非洲昏睡病、恰加斯病和利什曼病等疾病的重要病原体。在工业化国家（例如加拿大和美国），由于输血和器官捐赠，锥虫病的传播日益引起关注。特别是加拿大的新移民和从阿富汗返回的士兵处于危险之中。目前还没有针对这些病原体的疫苗，而且目前的药物有毒，价格也不切实际。此外，对这些药物的耐药性已经出现。该项目的总体目标是表征控制锥虫病原体线粒体基因表达和代谢的RNA编辑的基本和独特的分子过程。确定编辑机制、催化编辑的机制（编辑体）和编辑调控是这一领域的主要问题。该项目旨在使用计算和实验方法来阐明编辑体蛋白质如何协同工作。这些研究将从总体上扩展对RNA加工的认识，并有助于更好地理解RNA编辑及其调控的机制，最终目标是了解这一过程作为药物靶点的潜力。

Trypanosomatids are protozoan parasites that cause diseases in humans and livestock. They are important pathogens causing diseases that include African sleeping sickness, Chagas disease, and leishmaniasis. In industrialized countries (e.g. Canada and US), transmissions of trypanosomatids are of growing concern as a result of transfusion and organ donation. Particularly, new immigrants to Canada and soldiers returning from Afghanistan are at risk. There are no vaccines for these pathogens, and the current drugs are toxic and have unpractical prices. Also, resistance to these drugs has already emerged. The overall goal of this project is to characterize the essential and unique molecular process of RNA editing which controls the mitochondrial gene expression and metabolism in trypanosomatid pathogens. Determining the mechanism of editing, the machinery that catalyzes editing (the editosome), and the regulation of editing are the major questions in this field. This project is designed to use computational and experimental approaches to elucidate how editosome proteins work together. These studies will extend knowledge of RNA processing in general and help to better understand the mechanism of RNA editing and its regulation, with the ultimate goal of understanding the potentials of this process as a drug target.