# Functional characterization of striated fiber assemblins in malaria parasites

> **NIH NIH R21** · BOSTON CHILDREN'S HOSPITAL · 2024 · $221,250

## Abstract

PROJECT SUMMARY
Malaria is an important cause of illness and death worldwide, with most of these deaths resulting from
Plasmodium falciparum infection. The signs and symptoms of human malaria results from the asexual
replication of parasites in human red blood cells. During this clinically important blood stage, P. falciparum
parasites divide by schizogony – a process wherein components for several daughter cells are produced
within a common cytoplasm and then segmentation, a synchronized cytokinesis, produces individual
invasive daughters. The generation of the invasive daughter parasites, known as merozoites, occurs with
high fidelity, ensuring that each daughter has a single nucleus and the required organelles. The molecular
mechanism underlying this high fidelity of nuclear and organellar partitioning is incompletely understood in
Plasmodium.
Studies in the related Apicomplexan parasite Toxoplasma gondii identified a family of proteins, referred to
as striated fiber assemblins (SFAs), that are critical for parasite cell division. The SFAs are hypothesized to
form a connection between the centrosome of dividing nuclei and the newly forming apical ends of the two
daughter parasites during T. gondii endodyogeny. The P. falciparum orthologs of the SFAs, PfSFA1 and
PfSFA2, have been reported to be dispensable in a genome-wide transposon screen. In contrast to this
data, we demonstrate that these two proteins are essential for asexual replication in P. falciparum. Based
on our preliminary data, we hypothesize that PfSFA1 and PfSFA2 localize to a filament-like structure during
parasite segmentation. In the current proposal, we will test this hypothesize in a series of microscopy
assays. Furthermore, we will also evaluate the function of PfSFA1 and PfSFA2 by characterizing parasite
arrest and morphologic defects following inducible knockout. To gain a more complete understanding of the
molecular functions of PfSFA1 and PfSFA2, we will determine the direct protein interactions by co-
immunoprecipitation and the indirect or transient interactions by proximity labeling. By determining a robust
protein interaction network for the Plasmodium SFAs, we will establish the foundation to understand their
molecular function. We hypothesize that the SFAs proteins are critical for organization of segmentation
during the asexual replication of P. falciparum. Together, the proposed studies will interrogate the function
of these two essential proteins and directly identify their role during P. falciparum segmentation.

## Key facts

- **NIH application ID:** 10911222
- **Project number:** 5R21AI176570-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** JEFFREY D DVORIN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $221,250
- **Award type:** 5
- **Project period:** 2023-08-21 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911222

## Citation

> US National Institutes of Health, RePORTER application 10911222, Functional characterization of striated fiber assemblins in malaria parasites (5R21AI176570-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10911222. Licensed CC0.

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