Last Updated: 03/02/2025
Formation and function of the parasitophorous vacuole membrane in Plasmodium falciparum-infected erythrocytes
Objectives
The study aims to understand the formation of of the membrane of the parasitophorous vacuole (PVM) and the essential functions of the proteins present in this membrane during the growth of the malaria parasite Plasmodium falciparum in erythrocytes.
London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom
During entry into the erythrocyte, the parasite becomes surrounded by a membrane that forms the PV, the PV membrane (PVM), that envelops the parasite until the very last stages of the erythrocytic cycle. As the parasite grows, the PVM expands to accommodate the growing parasite. The PVM separates the parasite from the cytosol of the erythrocyte, but also forms a significant barrier to the export of parasite proteins to the host cell that are required for the survival of the parasite and the uptake of haemoglobin and nutrients from the erythrocyte.
The proposed research addresses the following questions:
- what is the origin of the phospholipids that make up the PVM when it is made and when it expands and how does the parasite phospholipid transfer protein PFA0210c affect this process; and
- what are the functions of the proteins in the PVM; and how does the PVM allow survival of the parasite inside the erythrocyte.
These questions will be addressed using a combination of genetic techniques newly adapted for use in Plasmodium parasites (Cas9-mediated gene modification and inducible gene removal using the rapamycin-inducible diCre system), biochemical approaches, and automated EM microscopy that allows 3D models of parasites to be produced. Together, the proposed experiments will provide insight into the function of the PVM and will reveal the essential functions of PVM proteins. Furthermore, this research could reveal entirely new targets for use in anti-malarial drug development.
The role of cholesterol in invasion and growth of malaria parasitesSynchronisation of Plasmodium falciparum and P. knowlesi In Vitro Cultures Using a Highly Specific Protein Kinase InhibitoUse of a highly specific kinase inhibitor for rapid, simple and precise synchronization of Plasmodium falciparum and Plasmodium knowlesi asexual blood-stage parasitesLipid transport proteins in malaria, from Plasmodium parasites to their hostsDistribution of malaria parasite-derived phosphatidylcholine in the infected erythrocyte
Feb 2018 — Jan 2023
$1.56M
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