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Last Updated: 07/11/2024
Investigating the role of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) variants in rosetting using CRISPR/Cas9
Objectives
This project aims to characterise a particular type of rosetting P. falciparum erythrocyte membrane protein 1 (PfEMP1) variants called domain cassette 11 (DC11) by using CRISPR/Cas9 technology to genetically modify PfEMP1 in live parasites, in order to study their function and interaction with host receptors.
Plasmodium falciparum is a single-celled parasite that causes the most severe forms of malaria in Africa. In humans, P. falciparum infects red blood cells (RBCs) and expresses variant antigens on the cell surface, which are referred to as P. falciparum erythrocyte membrane protein 1 (PfEMP1). Infected RBCs can adhere to non-infected RBCs and form rosettes, which block small blood vessels and are associated with severe malaria. As current research suggests that different DC11 variants can be recognised by a single antibody, this project will also aim to find conserved rosetting- mediating motifs among these variants and carry out serological assays to test for cross-reactivity. By defining the molecular and structural components of PfEMP1 variants, this work will contribute to elucidating the host-parasite interactions in P. falciparum malaria and to the development towards anti- rosetting therapies.
Oct 2023 — Sep 2026