Structure-function studies of a malaria drug-target in a model apicomplexan parasite
Supervisor: Dr Lilach Sheiner, School of Infection & Immunity
Apicomplexan parasites cause diseases, including toxoplasmosis and malaria, that require new drugs due to drug-resistance and sub-optimal performance of frontline drugs. Apicomplexan mitochondrial pathways, such as respiration and translation, are critical for parasite survival and are divergent from host pathways. For these reasons, the apicomplexan mitochondrial functions have been prime targets for drug, such as atovaquone (targeting the respiratory chain) and chloramphenicol (targeting the mitochondrial translation pathway). Despite this proven potential to inform drug discovery very little is known about how these pathways work. Our lab has been investigating these pathways through (1) discovering what proteins make their enzymes; (2) deciphering the enzymes structures; and (3) understanding how do structure and protein-content contribute to function.
This project will use molecular biology, cell-biology, biochemistry and structural biology techniques to address the above questions focusing on one of the enzymes in these pathways. The student will gain experience in parasite and mammalian cell-culture, parasite genetic manipulation, cell and organelle biochemistry, different types of microscopy methods and will gain insight into structural biology via cryoEM through our collaborations (or via co-supervision if the student chooses so).