# PfVP1, a battery of the malaria parasite, is critical for ring stage development

> **NIH NIH R21** · DREXEL UNIVERSITY · 2021 · $225,586

## Abstract

Project Summary
Malaria remains a major global health concern and the control progress has run into a serious
bottleneck in recent years. Each year, more than 3 billion people are living at risk of contracting
malaria, 200 million people are infected and half a million people die from malaria. As malaria
parasites rapidly develop resistance to available antimalarial drugs, a better understanding of
fundamental biology is urgently needed. In the asexual blood stages, malaria parasites mainly
reply on glycolysis for energy since the parasite's mitochondrion does not perform oxidative
phosphorylation to produce ATP. They also contain membrane bound proton pumping
pyrophosphatases (mPPases), which use pyrophosphate, the by-product of over 200 cellular
reactions, as the energy source to pump protons across a membrane. We have previously
knocked out PfVP2 (PF3D7_1235200) whereas PfVP1 (PF3D7_1456800) has been predicted
to be essential. Using a CRISPR/Cas9 mediated genetic tagging/conditional knockdown, we
have found that PfVP1 is localized to the parasite plasma membrane and is essential for ring
stage development. In this application, we hypothesize that PfVP1 uses pyrophosphate as an
alternative energy source to sustain a proton electrochemical gradient in the ring stage
development of Plasmodium falciparum. We will test this hypothesis in the following aims.
Aim 1, Assess the activity of PfVP1 as an integral membrane proton-pumping pyrophosphatase.
Aim 2, Define the function of PfVP1 in ring stage parasites. Together, this proposal will uncover
important insights of ring stage development and bioenergetics, critical yet understudied
aspects of parasite biology. If successful, the studies proposed here will provide direct evidence
that an alternative energy source is critical for early stage development of a malaria parasite in
RBCs. Finding a critical molecular target at the ring stage will also facilitate target-based drug
development in future to better inhibit metabolically less active parasite forms that are often
resistant to current antimalarials.

## Key facts

- **NIH application ID:** 10116730
- **Project number:** 1R21AI156735-01
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Hangjun Ke
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,586
- **Award type:** 1
- **Project period:** 2020-11-10 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116730

## Citation

> US National Institutes of Health, RePORTER application 10116730, PfVP1, a battery of the malaria parasite, is critical for ring stage development (1R21AI156735-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10116730. Licensed CC0.

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