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Kirsten Heiss (2014-2017)

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 (project together with Ann-Kristin Mueller)

The intracellular development and differentiation of the Plasmodium parasite in the host liver is a prerequisite for the actual onset of malaria disease pathology. 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 more than 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 herein proposed project is to broaden the knowledge of the fundamental dynamic cellular processes of the intrahepatic malarial parasite with both specific host-cell factors and compartments. The differentiating and replicative intrahepatic 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 functional characterisation of specific proteins known to reside in the parasitophorous vacular membrane (PVM) where they are suggested to recruit crucial energy sources from the host compartment to ensure survival and expansion intrahepatically. In a parallel approach we hope to be able to interconnect the role of those PVM-resident proteins to family members of the parasitic vesicular trafficking network localising to the parasitophorous vacular compartment and potentially across the PVM to other compartments of the hepatic environment. The results of this study can be exploited for the development of new approaches to prevent both malaria disease and infection. It will ultimately improve our understanding of different cell-biological aspects of host/pathogen interactions.