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Understanding the role of glycerol in triggering parasite differentiation

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Trypanosoma brucei (T. brucei) is an extracellular parasite and the causative agent of African trypanosomiasis. The protozoan exhibits a complex life cycle taking place in an insect vector and a mammalian host and requires morphologic and metabolic adaptations in order to survive in distinct environments. T. brucei can occupy the bloodstream of its mammalian host as two forms: proliferative slender forms and cell-cycle arrested stumpy forms. Differentiation of slender forms to stumpy forms occurs in response to activation of a density-sensing pathway elicited by an elusive Stumpy Induction Factor (SIF) produced by the parasites. In my thesis we explore a potential impact of parasite-derived metabolites in the in vitro differentiation of slender forms into stumpy forms, with emphasis on glycerol. For this purpose, several biochemical and cellular assays were performed to monitor this developmental transition. In order to elucidate the molecular mechanism underlying the differentiation of slender forms into stumpy forms, we also generated mutant parasite lines for the transport and production of metabolites and characterized their phenotypes.

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Trypanosoma brucei Differentiation into stumpy forms Stumpy Induction Factor Glycerol Glycolysis

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