Mitochondrial metal uptake in Toxoplasma gondii

Supervisors:

Dr Clare Harding, School of Infection & Immunity
Prof Konstantinos 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 acquires all nutrients it needs for replication from its host cell. Within the parasite, the unusual mitochondrion requires iron and copper. Iron is used in a range of essential processes while copper is required for energy generation, but how these metals are transported into the mitochondrion is currently unknown.
This project will focus on two transporters which we believe transport metals into the mitochondrion. The work will start by validating the transport activity of these proteins through complementation of yeast mutants and quantifying growth. It will also use high-throughput plate-based assays to assess changes in yeast metabolism. Transport activity will be confirmed by metal analysis of isolated mitochondria. After validation, the project will 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 metabolism by measuring respiration and metabolomics. Overall, this project will identify essential parasite transporters, with a view to understanding the role that these play in metabolism.