Identifying key metabolic pathways required for Toxoplasma gondii infection
Toxoplasma gondii is a protozoan parasite that causes acute disease in immunocompromised individuals and may asymptomatically infect as much as one-third of the world's population. While drugs are available for treating acute (active) infections, none is effective in clearing chronic infections.
This project will investigate the role of metabolic pathways that may be important for survival of T. gondii chronic stages with a view to identifying new drug targets and understanding how these parasites maintain long-term latent infections.
Students will gain experience in parasite/mammalian tissue culture, in the parasite molecular genetics and novel mass spectrometric techniques to determine the changes as these parasites invade and propagate within nucleated host cells. Cultured parasites or infected host cells will be labeled with various stable isotope (13C)-labeled carbon sources (i.e. sugars, amino acid, fatty acids) and the metabolic dynamics followed using mass spectrometry and NMR to follow the incorporation of heavy carbon isotopes into key metabolic intermediates.
These experiments will also be performed using T. gondii mutants that lack key metabolic enzymes. These studies will allow us to identify pathways essential for infectivity of specific parasite developmental stages, as well as pathways that are likely to be redundant.
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