Identification of essential host cell factors for the survival of the obligate intracellular apicomplexan parasite Toxoplasma gondii

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The phylum Apicomplexa is composed of over five thousand parasitic species, which cause several diseases in humans and animals. These parasites are obligate intracellular and highly dependent on host cell factors. Whereas invasion of the host cell occurs in an active process independently of host cell phagozytosis that involves the parasites ability to glide, the intracellular survival of the parasite highly depends on host cell metabolism and the ability of the parasite to interfere, modulate and use signaling cascades of the host cells for its own purpose. While knowledge of essential parasite proteins involved in these mechanisms is increasing current understanding of the specific interaction partners and host cell factors contributing to pathogenesis is still in its infancy. The purpose of this proposal is to perform a genome wide RNAi screen on HeLa cells that will serve as host cells for Toxoplasma gondii in order to identify essential factors derived from the host cell, needed for invasion, intracellular replication and egress. Therefore RNAi-treated HeLa cells will be infected with T.gondii and propagation of the parasite will be followed over time. We aim to identify factors that are essential for successful propagation of the parasite whereas host cell viability itself is not affected. This will not only broaden our knowledge on host-parasite interactions but might also lead to the identification of new drug candidates against apicomplexan parasites.