Malaria intrahepatic interactions and trafficking: Deciphering the molecular machinery driving vesicular trafficking and membrane fusion between the hepatic host environment and malarial parasite for parasitophorous vacular membrane dynamics

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The intracellular development and differentiation of the Plasmodium parasite in the host liver is a prerequisite for the actual onset of malaria disease. Since liver stages are clinically silent and can be completely eliminated by sterilising immune responses, they are promising targets for urgently needed innovative antimalarial drugs and/or vaccines. Discovered almost 60 years ago, these stages remain poorly understood regarding their molecular repertoire and interaction with their host cells in comparison to the better accessible pathogenic erythrocytic stages. The overall aim of this proposed project is to broaden the knowledge of fundamental dynamic cellular processes of the intrahepatic liver stage parasite with host cell compartments. The differentiating and replicative intracellular parasite resides in a membranous compartment called parasitophorous vacuole, separating it from the host cell cytoplasm in addition to its own plasma membrane. In the course of our proposed studies we aim at focussing on the characterisation of distinct proteins known to reside in the parasitophorous vacular compartment and at the same time deciphering potential members of the trafficking network from and to the hepatic environment. The results of this study can be exploited for the development of new approaches to prevent malaria disease and besides will improve our understanding of different cellbiological aspects of host/pathogen interactions.