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Publications in VIVO

Hu, Ke Whitman Center Scientist, Whitman Center


Toxoplasma gondii is one of the most successful parasites on earth, permanently infecting nearly 20% of the global population. Infections in immunocompromised individuals and the unprotected fetus have devastating consequences, including the development of lethal Toxoplasma encephalitis. Besides being an important human parasite itself, T. gondii is a model for its ~6000 relatives in the Phylum Apicomplexa, including the malaria parasites. Although toxoplasmosis is a very severe disease, its pathogenesis is simple: tissue destruction by reiteration of the parasite’s lytic cycle of host cell invasion, parasite replication, and egress. The parasite’s cytoskeleton (literally, the "skeleton" of a cell), formed of several distinct types of biopolymers, is required for every step in this cycle. It drives motility for invasion and egress, provides strength for the cortex (for withstanding the extreme deformation the parasite experiences as it moves in and out of the host cell), and provides the framework for the unusual “born-within” type of parasite replication. The “life-style” of this extraordinarily successful parasite therefore depends on a specialized and unusual set of cytoskeletal properties. My group focuses on understanding the construction and function of the structural framework of this invasion machine. We take advantage of the highly ordered cytoskeletal architecture and streamlined motility of T. gondii to uncover fundamental principles for structural inheritance and force transmission. At the same time, we combine the investigation of basic processes with the discovery of novel drug targets for T. gondii and malaria parasites. Specific questions include: How does a cell reproducibly establish its characteristic cellular architecture? How does the cytoskeleton control the shape, mechanical strength, and biogenesis of the cellular cortex? How do internal and external signals regulate force generation to drive directional cellular movement? We combine molecular genetics, proteomics, super-resolution imaging and biophysical techniques to answer these questions.

selected publications