# Functional investigation of a novel and essential subcellular compartment in Plasmodium falciparum transmission stage parasites

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $756,280

## Abstract

PROJECT SUMMARY
Malaria is an important cause of illness and death worldwide, with most of these deaths resulting from
Plasmodium falciparum infection. Successful completion of the P. falciparum life cycle and infection of a
new human host requires transmission. During the asexual blood stage in human red blood cells, a small
population of parasites differentiates into transmission forms known as gametocytes. These gametocytes
can complete the sexual stage of the parasite life cycle following ingestion by a mosquito. Gametocyte
maturation in human red blood cells occurs over 10-12 days and is associated with major changes in
cellular morphology and rigidity. A newly discovered protein PfBLEB (for Baso-Lateral Expansion Boundary)
is essential for mature gametocyte formation. In asexual parasites, PfBLEB is part of the basal complex, a
ring-like multi-protein complex at the leading edge of the inner membrane complex. While PfBLEB is
dispensable for both asexual replication and gametocyte commitment, it is essential for gametocyte
development. PfBLEB-knockdown or knockout gametocytes arrest during maturation and are non-
transmissible. Furthermore, the PfBLEB-deficient gametocytes have gross morphologic changes with
defects in major cytoskeletal features of the maturing transmission-stage parasite, including the inner
membrane complex and subpellicular microtubules.
In gametocytes with normal PfBLEB expression, PfBLEB defines a new subcellular compartment within the
parasite, demarcating the regions of the parasite plasma membrane that are devoid of the underlying inner
membrane complex. The PfBLEB-compartment is essential for gametocyte development, but the function
and protein constituents of this newly discovered subcellular compartment remain unknown. The goal of the
current application is to define and genetically evaluate the protein components of the PfBLEB compartment
and to understand the functional defects in PfBLEB-deficient gametocytes. The first aim will utilize proximity
labeling and reverse genetics to explore the PfBLEB-containing compartment. The second aim will utilize
multiple imaging and microfabrication techniques to gain a functional understanding of what processes are
abnormal in PfBLEB-deficient gametocytes. Together, the proposed studies will add a new layer to our
molecular understanding of gametocyte development in P. falciparum.

## Key facts

- **NIH application ID:** 10791849
- **Project number:** 5R01AI169648-03
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** JEFFREY D DVORIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $756,280
- **Award type:** 5
- **Project period:** 2022-03-04 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10791849

## Citation

> US National Institutes of Health, RePORTER application 10791849, Functional investigation of a novel and essential subcellular compartment in Plasmodium falciparum transmission stage parasites (5R01AI169648-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10791849. Licensed CC0.

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