BSB PhD Exit Seminar: Elucidating and exploiting the mitochondrial electron transport chain of T. gondii parasites

Jenni Hayward, van Dooren Group, BSB, RSB

As you read this abstract, your lungs are (I hope!) bringing live-sustaining oxygen into your body. Oxygen is required by our cells for one key purpose – to act as the final electron acceptor in the mitochondrial electron transport chain (ETC). The ETC is composed of a series of membrane-bound multi-protein complexes that work cooperatively to generate energy (ATP) via oxidative phosphorylation. Toxoplasma gondii parasites are unicellular and as such do not have lungs, but don’t let their petite size fool you! T. gondii parasites chronically infect up to a third of the global human population and can cause serious disease in immunocompromised or pregnant individuals. The ETC is one of the few validated drug targets in T. gondii parasites, and yet little was known about precisely how this important pathway differs from that of humans. In my PhD, I investigated how the ETC complexes of T. gondii parasites differ from their human counterparts, and whether these differences can be exploited therapeutically. In this seminar, I will highlight some of my key findings about T. gondii ETC Complexes III and IV, and in doing so introduce a Seahorse XFe96 flux analyser-based method I developed to investigate ETC function. Finally, I will show how I adapted this method to screen the Medicines for Malaria Venture “Pathogen Box” compound library to identify and determine the molecular targets of novel inhibitors of the T. gondii ETC.