How are Plasmodium falciparum proteins directed to the parasite translocon to reach the host cell?

This project will study how Plasmodium falciparum, the deadliest malaria-causing parasite, exports its proteins into the host red blood cell. Although still poorly understood, this process is essential for the parasite survival and pathogenicity, thus providing an attractive target for the development of antimalarial drugs. Recently, a key role in protein export has been ascribed to a newly discovered PTEX translocon located at the parasitophorous vacuole membrane surrounding the parasite. To unravel the objective, Michał Pasternak will dissect the events preceding the translocation step: – How do exported proteins enter the endoplasmic reticulum (ER)? – How are they loaded into vesicles for their subsequent export from the ER? – How do they then reach the PTEX translocon in order to enter the erythrocyte? To tackle these questions, Michał Pasternak will use a combination of genome editing, biochemistry and super-resolution light microscopy. He will also develop the first protocol to study protein export in living parasites at unprecedented resolution, using lattice light-sheet microscopy. Finally, Pasternak will use the EM cryo-tomography to solve the structure of the PTEX translocon in situ.

Basic Science

Jul 2018 — Jul 2022

$325,992

United Kingdom