Digestive vacuole biogenesis in the malaria parasite

Columbia University Health Sciences, New York NY

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Abstract

This proposal aims to understand the biogenesis of the digestive vacuole (DV) of the malaria parasite, Plasmodium falciparum. This acidic, lysosomal-like organelle is responsible for the degradation of large quantities of hemoglobin ingested from the host erythrocyte. The DV is also the site of action of the largest and historically the most clinically useful family of antimalarial drugs, the 4-aminoquinolines. Despite the importance of this organelle to parasite development and antimalarial chemotherapy, little is currently known about how both biosynthetic parasite proteins and components of the host cell cytosol are delivered to the DV during the intraerythrocytic lifecycle. I propose to determine which trafficking steps are essential for the transport of parasite and host cell proteins to the DV by genetic and chemical disruption of defined stages of intracellular transport. These studies will enable us to address the hypothesis that one pathway of parasite protein trafficking to the DV relies upon the Sec and Vps components of protein secretion and sorting. Our second major hypothesis is that uptake of hemoglobin and some host erythrocyte cytosol components proceeds via dynamin-dependent endocytosis.