# Diversity Supplement for Elucidating the trafficking mechanisms of effector proteins to the Plasmodium infected red blood cell

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2020 · $64,183

## Abstract

RESEARCH SUMMARY [PARENT GRANT]
Plasmodium falciparum is a deadly human parasite that causes malaria and is responsible for nearly 450,000
deaths every year. Malaria is endemic in large regions of the world, home to about 4 billion people and it affects
~250 million people annually. There are no effective vaccines against malaria and antimalarial drugs are the
mainstay of treatment. At this time, the parasite has gained resistance to all clinically available antimalarial drugs
and these drug resistant strains are spreading throughout the world, threatening all the progress that has been
made against this disease in the last decade. Therefore, it is imperative that we constantly generate new drugs
and identify potential drug targets to stay ahead of this nefarious disease. The clinical manifestations of this
devastating parasitic disease, including death, are caused by the growth of P. falciparum within the host red
blood cell (RBC). To build a suitable habitat for growth inside RBCs, the malaria parasite completely transforms
the host cell. It changes the metabolism of the RBC, makes the RBC more rigid such that it is harder for the
infected RBC to pass through capillaries, modifies the RBC membrane to allow for favorable movement of
nutrients, and alters the binding properties of the RBC so that the infected cell can bind to the endothelial cells
lining blood vessels. The sum of these changes leads to disease and death, for instance, binding of the P.
falciparum infected RBC to endothelial cells can clog blood vessels in the brain leading to clots that eventually
result in death. The subjugation of the infected RBC is accomplished through the action of several hundred
proteins that the parasite transports to the host cell via poorly understood mechanisms. The export of parasite
effector proteins is essential for transforming the RBC and therefore, for causing disease. Parasite effector
proteins that are synthesized in the parasite cytoplasm need to be transported across three or four cellular
membranes in order to reach their site of action in the host RBC. The molecular mechanisms that recognize,
sort, and transport these parasite effectors to the infected RBC remain to be identified. The proposed studies
aim to unravel the molecular processes that govern key early events that set parasite effectors on the path to
the host RBC. We will pursue two aims to accomplish this goal. First, we will generate conditional mutants of
proteins in the endoplasmic reticulum of the parasite that are potentially required for export of parasite effectors.
The mutants will be analyzed using genetic, cellular, and biochemical approaches to determine their roles in the
export of parasite proteins. Second, we will take an unbiased interactome screening approach that uses a
proximity-based labeling approach and discover proteins that usher exported proteins to their site of action in
the host RBC. Attaining the objectives of the research program will reveal key and u...

## Key facts

- **NIH application ID:** 10077624
- **Project number:** 3R01AI130139-03S1
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Vasant Muralidharan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,183
- **Award type:** 3
- **Project period:** 2018-01-05 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077624

## Citation

> US National Institutes of Health, RePORTER application 10077624, Diversity Supplement for Elucidating the trafficking mechanisms of effector proteins to the Plasmodium infected red blood cell (3R01AI130139-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10077624. Licensed CC0.

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