Host-Pathogen Co-evolution

Our work focuses on mechanisms of resistance to the ubiquitous intracellular protozoan parasite, Toxoplasma gondii, a malaria relative, which infects about 40% of the human race. We study immunity of mice against T. gondii because the primary hosts of the parasite, in which it makes gametes and does meiosis, is cats, so the T. gondii life cycle, and its abundance in our environment, is thus driven by an infectious cycle between cat and mouse. Mouse immunity against T. gondii is based on a mechanism absent in humans, inducible GTPases (IRG proteins) that cooperatively destroy the vacuole in which the parasite lives. This mechanism has in turn been targeted by the parasite, via a family of kinases that inactivate IRG proteins. Both the IRG proteins and the kinases are massively polymorphic, consistent with a complex co-evolutionary dynamic. Our work stretches from ecological studies on wild mice to cell biological, biochemical and structural studies.