African sleeping sickness, Chagas disease and leishmaniasis are potential lethal human and cattle diseases caused by kinetoplastids Trypanosoma brucei, cruzi and Leishmania respectively, which belong to a group of unicellular eukaryotic parasites. There is an urgent need for discovery of novel, more effective and safer drugs against these neglected tropical diseases. We chose to target ribosome translation machinery, one of the most essential machineries for the parasite survival. Ribosome is a hybrid RNA-protein complex that is responsible for the translation of mRNA, a pivotal step in cell protein synthesis. We endeavor to assess the druggability of the parasite-specific sites in this complex that could serve as potential targets for safer and more efficient therapeutic drugs.

Therefore, their disruption could inhibit the protein translation in the parasitic pathogen without hindering translation in the host cells. Our goal is functional and structural characterization of these kinetoplastid-specific features that could serve as potential drug targets. To that end, we use state-of-the-art cryo-electron microscopy, the technique that was awarded the 2017 Chemistry Nobel prize, to get insight into the specific structural features at high-resolution. We corroborate structural studies with in vivo assays in the parasites to uncover mRNA translation regulation. We aim to identify the starting points for further drug development of molecules with antiparasitic effect.

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