Characterizing a novel Plasmodium cytoskeletal protein

Plasmodium falciparum is a pathogenic eukaryote in the phylum Apicomplexa with a complex life cycle that alternates between Anopheles mosquitoes and humans. During the blood stages of the P. falciparum life cycle, a single merozoite is known to invade a human red blood cell (RBC). Over the course of 48 hours, the parasite’s genetic material and organelles are multiplied via schizogony to form 20-36 merozoites. During infection, a small subset of these parasites (~0.2-1.0%) commit and differentiate into transmissible male and female gametocytes through a staged process called gametocytogenesis. These two processes require elaborate, controlled cytoskeletal remodeling. The Plasmodium cytoskeleton comprises the pellicle, which includes the parasite plasma membrane and a specialized organelle referred to as the inner membrane complex, and the subpellicular network that constitutes microtubules and a family of intermediate filament-like proteins called alveolins. These structures together are responsible for partitioning cytoplasmic contents during segmentation, conferring cell shape and rigidity for daughter merozoites and developing gametocytes, and providing essential structural support during gliding motility and RBC invasion.

A novel Plasmodium cytoskeletal protein, PfFIG (Found In Gametocytes), was recently discovered during a study of the basal complex during blood stage P. falciparum infection. Preliminary data demonstrate that PfFIG is important for asexual replication and is associated with microtubule dynamics in segmenting schizonts and maturing gametocytes. However, the functional role of PfFIG during the Plasmodium blood stages of human malaria infection is not yet known. Using inducible knockout (iKO) systems together with super-resolution and cell viability assays, the role of PfFIG (PF3D7_1435600) in P. falciparum daughter cell segmentation and gametocyte maturation will be characterized. This will elucidate its unique role in Plasmodium microtubule dynamics, specifically as it contributes to cell shape and facilitates life stage transitions. Additionally, immunoprecipitation and proximity-labeling experiments will be performed to map the PfFIG interactome, identifying proteins of interest for future study and characterization. This research aims to broaden understandings of the core cellular machinery utilized by Plasmodium to carry out its unique life cycle. Specifically, study of Plasmodium-specific cytoskeletal proteins and their role across parasite life stages may bring us closer to targeting these proteins with antimalarial drugs.

NIH Project details

Basic Science

Feb 2024 — Jan 2027

$41,923

United States