Structural and functional organization of the editosome in trypanosomatids

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The overall objective of this project is the characterization of an essential and unique molecular process of RNA editing that controls the mitochondrial gene expression and metabolism in trypanosomatids.  Trypanosomatids are protozoan parasites that cause diseases in humans and livestock. They include the causal agents of human African sleeping sickness, Chagas' disease, and Leishmaniases (Trypanosoma brucei group, T. cruzi, and Leishmania species, respectively).  Most drugs are increasingly ineffective due to toxicity and development of resistance.  RNA editing occurs in all members of this family of trypanosomatid pathogens and it is a potential chemotherapeutic target.  Elucidation of the mechanism of editing, the machinery that catalyzes editing (the editosome), and the regulation of editing are the major problems to be solved in this field.  This project is designed to provide an understanding of spatial organizations of a family of editosome proteins within this structure in order to elucidate its function in T. brucei. It is anticipated that this project will extend knowledge of RNA processing and gene expression mechanisms in general and contribute to future structural studies aimed at finding patentable drugs that might target the editosome complex in all three major trypanosomatid pathogens.  The proposed project will focus this substantial activity at McGill University on a training and research program in an exciting area of RNA biology and infectious diseases to achieve a synergy that will provide for responding to future emerging diseases.