Mitochondrial metal uptake in Toxoplasma gondii and its role in metabolism
Supervisors:
Dr Clare Harding, School of Infection and Immunity
Prof Kostas Tokatlidis, School of Molecular Biosciences
Summary:
Toxoplasma gondii is a ubiquitous parasite which infects 20-30% of humans worldwide. Usually asymptomatic, infection can cause severe disease in pregnant or immunocompromised people. As an intracellular parasite, Toxoplasma steals its nutrients from its host cell. These nutrients, including the essential transition metals iron and copper, are needed in the parasite’s unusual mitochondrion to produce energy. However, the role of these metals and how they enter the parasite mitochondrion remains unknown. This project will focus on two transporters which we believe transport metals into the mitochondrion. We will first validate the transport activity of these proteins through complementation of yeast mutants and quantifying growth using high-throughput plate-based assays to assess changes in mitochondrial metabolism. Transport activity will be confirmed by metal analysis of isolated mitochondria. The project will then move into Toxoplasma to identify how loss of these transporters affects the parasite growth and fitness. Using the data from yeast, the project will identify the role of mitochondrial-metal transporters on parasite metabolism by measuring respiration and performing both untargeted metabolomics and flux analysis. Overall, this project will characterise essential parasite transporters and determine the interaction between mitochondrial metal uptake and metabolism.