|Education||BS, University of Massachusetts, Amherst|
The apicomplexan parasite Toxoplasma gondii infects about one third of the world’s population and is the model organism for the phylum Apicomplexa that includes Plasmodium due to its ease of cell culture and genetic manipulation. The disease caused by T. gondii, toxoplasmosis, mainly threatens pregnant women and immunocompromised patients (AIDS, transplant, etc.). Pregnant women will suffer miscarriage or development defects of the fetus, and immunocompromised patients may die from fatal encephalitis. T. gondii can invade almost any vertebrate cell and then replicates in an immune privileged compartment called the parasitophorous vacuole (PV) that sequesters it not only from host cell defenses but also from host cell nutrients. As a parasite, T. gondii has lost many biosynthetic genes from its genome, but has expanded its repertoire of genes involved in acquiring nutrients from its host. Currently, the specific mechanisms by which T. gondii scavenges nutrient rich host vesicles are unknown.
Treatment of toxoplasmosis with pyrimethamine and sulfadiazine indiscriminately blocks both host and parasite DNA synthesis by inhibiting dihydrofolate reductase and dihydropteroate synthetase. However, side effects and hypersensitivity to the drugs can develop. My project focuses on unveiling the specific proteins T. gondii uses to internalize host cell vesicles into the PV, which will expose potential drug targets that could be inhibited without any adverse side effects. Additionally, I will be targeting proteins, like acyl-CoA: cholesterol acyltransferase, that we believe are crucial to T. gondii’s nutrient storage. By focusing on the nutrient acquisition and storage processes in T. gondii, I hope to find better drug targets that would lead to therapies with minimal side effects for patients.