Last Updated: 10/03/2023
Structural and functional characterization of Plasmodium falciparum rhoptries and its proteins
Objectives
- To leverage the latest developments in cryo electron tomography and cryo focused ion beam milling to achieve sub nanometer resolution of rhoptry ultrastructures during different stages of invasion.
- To determine the near-atomic structure of the high-molecular-weight rhoptry complex known as the RhopH complex, which inserts into the erythrocyte membrane and is essential for nutrient uptake.
Malaria is caused by protozoan parasites of the Plasmodium species, which during their lifecycle infect human erythrocytes. Like all apicomplexan parasites, P. falciparum has specialized organelles that are essential to infectivity. One of these organelles are the rhoptries, which eject proteins, lipids and membranes into the erythrocyte upon invasion that aid in establishing an exomembrane system and building a new trafficking network to acquire the nutrients necessary for intracellular replication of the parasite. The molecular processes mediating rhoptry content expulsion and nutrient acquisition remain poorly understood.
The molecular characterization of rhoptry ultrastructure pre-, mid- and post-infection, combined with near-atomic structures of essential rhoptry proteins will deepen our understanding of how the parasite invades and manipulates the host-cell to establish intracellular infection. Elucidating the essential mechanisms of invasion and nutrient acquisition in malaria parasites will pave the way for developing drug mediated interventions to block parasite survival. Additionally, the novel approaches developed in the pursuit of the proposed research will provide much-needed tools for overcoming longstanding barriers to high resolution structural studies across the field of parasitology.
Jan 2021 — Nov 2021
$118,307
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