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Last Updated: 18/06/2024
Erythrocyte invasion in malaria: molecular mechanism to precision therapeutics
Objectives
This proposal will use structural insights to guide experiments to understand the function of PfRCR in erythrocyte invasion, and to guide development of future vaccines and therapeutic antibodies. Over the next five years the project will:
- Determine structures of PfRCR and PfRIPR and understand whether complex formation is necessary for invasion.
- Understand molecular mechanisms of the most invasion-neutralising human antibodies targeting PfRH5, PfCyRPA and PfRIPR.
- Determine how PfRH5 induces calcium flux in erythrocytes.
- Use structural insights to design improved therapeutic monoclonal antibodies and vaccine immunogens targeting PfRCR.
Principal Institution
Principal Investigators / Focal Persons
Rationale and Abstract
Invasion of erythrocytes is one of the most critical steps in the life cycle of the malaria parasite. Prevent erythrocyte invasion, and we can prevent parasite growth, disease symptoms and transmission. Essential for erythrocyte invasion is the PfRCR complex of Plasmodium falciparum, consisting of PfRH5, PfCyRPA and PfRIPR. These studies will deepen existing understanding of this critical event in erythrocyte invasion. They will reveal the human antibody response to PfRCR vaccination and use this insight to guide design of the malaria therapeutics of the future.
Thematic Categories
Date
Jan 2021 — Dec 2025
Total Project Funding
$2.82M
Funding Details
Project Site
Related Resources
