Trafficking and sorting of proteins to the parasitophorous vacuolar membrane of the malaria parasite P. falciparum: Exp1 as a model.

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The human malaria parasite P. falciparum invades and propagates within mature red blood cells. During invasion, the parasite envelops itself within a so-called parasitophorous vacuolar membrane (PVM), which acts as an interface between parasite and host cell, and is implicated in a number of processes important for parasite propagation. To this end, the parasite synthesises a number of proteins which intercalate into the PVM and are essential for parasite survival. However, it is so far unclear how exactly these proteins are both trafficked and sorted from the parasite to the PVM. In this project, using a number of complementary techniques, we aim to address this question and elucidate both the signals and mechanisms utilised to enable protein transport to the PVM. As a model protein, we shall firstly dissect the sorting signals and mechanisms required for the transport of the Exported Protein 1 to the PVM. Principles uncovered during this initial study will then be used to study the trafficking of further PVM-resident proteins such as members of the ETRAMP family. As protein transport to the PVM is a process underlying intra-erythrocytic development of the parasite and the subsequent pathology in the human host, any novel pathways may prove to be a chink in the parasite’s armour which may later be targeted for development of anti-parasitic drugs.