The egress of malaria gametocytes from the red blood cell following parasite transmission to the mosquito

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Sexual reproduction of the malaria parasite is initiated following its transmission from the human host to the mosquito vector during a blood meal. The sexual stages are the only life-cycle stages of the parasite that are able to establish an infection in the mosquito and thus play an important role for spread of the tropical disease. The egress of sexual precursor cells, the gametocytes, from the enveloping host erythrocyte is triggered by stimuli of the mosquito midgut and involves the rupture of two membranes, the erythrocyte membrane and the membrane of the parasitophorous vacuole. Gametocyte egress is crucial for the formation of gametes, but the underlying molecular mechanisms are up to date not well understood. It is the aim of this proposal to dissect on the ultrastructural level the distinct steps of gametocyte egress from the erythrocyte in the human malaria parasite Plasmodium falciparum. Our particular focus will lie on investigating the functions of proteases and phopholipases in membrane disintegration and on determining the potential role of parasite-derived perforins in the rupture of the parasitophorous vacuole membrane. Techniques include inhibitor assays as well as reverse genetics and dominant negative expression approaches in combination with confocal laser scanning and electron microscopy.