Last Updated: 25/02/2025
Dissection of the function of the Plasmodium falciparum protein families EBL and RH during erythrocyte invasion
Objectives
To determine if the families have distinct roles, this project will characterise invasion of single and double protein knock-outs using advanced video microscopy tools, and visualise the localisation of proteins simultaneously using fluorescence microscopy.
Plasmodium falciparum causes >90% of malaria mortality, killing over 400,000 people annually. To multiply, P. falciparum parasites must invade human erythrocytes. Invasion begins with attachment of the parasite to the erythrocyte, followed by reorientation to position the parasite to invade. These early steps depend on two families of membrane proteins: Erythrocyte Binding Like proteins (EBLs) and Reticulocyte Binding Protein Homologues (RBLs). There are four members of each family in the P. falciparum genome that can individually be deleted without blocking invasion. EBLs and RBLs are therefore believed to be functionally interchangeable, but this has never been systematically investigated and all Plasmodium parasites maintain both families suggesting considerable selection pressure against loss of one family. New antimalarial therapies are needed as P. falciparum has developed resistance to every antimalarial drug available and the only licensed malaria vaccine is <40% efficient. Invasion is essential for parasite survival, so a better understanding of the functional redundancy of ligands involved in invasion could aid development of multi- target vaccines or therapies.
Oct 2020 — Mar 2024
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