Trypanosomatid parasites cause lethal diseases, such as visceral leishmaniasis and Chagas disease, infecting ~7 million people worldwide. Available drugs for these diseases suffer from severe toxic side effects and emergence of drug resistance. The mitochondrion, the powerhouse of the cell, harbours an energy-converting protein machinery called complex III, which is essential for parasite survival and a confirmed drug target, but its three-dimensional structure is unknown. Using tomographic methods at the electron microscopy unit of the University of Helsinki, we will determine how the parasite achieves a tight packing of complex III molecules inside its powerhouse. Using high-resolution electron microscopy, we will determine the molecular structure of complex III bound to anti-trypanosomatid inhibitors to reveal how they block the protein complex. This project will expand our understanding of a fundamental cell biological process in human parasites and inform future drug development.

2025

2029