Structural dynamics and developmental regulation of the editosome complex in trypanosomatids

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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.