# Harnessing the Unique Biogenesis of the Apicomplexan plastid organelle forAntimalarial Targets

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $584,948

## Abstract

Abstract/ Project summary
 Malaria caused by Plasmodium spp parasites is a leading cause of morbidity and mortality globally. The
emergence of resistance to frontline antimalarial drugs threatens to wipe out progress made in disease control
and set back efforts toward eradication. New drug targets are urgently needed to circumvent current resistance
mechanisms. The unique biology of Plasmodium spp and related human pathogens, compared to their
mammalian hosts, can be leveraged to discover pathogen-specific drug targets that minimize host toxicity. A
prime example of the pathogen's distinct biology is the non-photosynthetic plastid organelle, or apicoplast.
Critical proteins that govern the biogenesis – growth, division, and inheritance – of the apicoplast during
parasite replication remain mysterious, though compounds that block apicoplast biogenesis, such as
clindamycin, are used clinically to prevent malaria and treat malaria, babesiosis, and toxoplasmosis. Because
apicoplast biogenesis is required in every proliferative stage and conserved among parasites, it presents
untapped opportunities to discover pathogen-specific drug targets effective across life stages and against
multiple pathogens. Our long-term goal is to discover the molecular mechanisms of apicoplast biogenesis and
exploit the machinery involved as antimalarial targets. The objective of this project is to identify and functionally
characterize genes required for apicoplast biogenesis in blood-stage P. falciparum, since many essential, but
as yet unidentified, genes are required for this complex process. My laboratory has laid the foundation to
achieve this objective by successfully designing innovative approaches to discover new molecular players.
This proposal will identify previously unknown genes required for apicoplast biogenesis using a new forward
genetic screen and begin characterizing the biochemical and cellular functions of newly-validated genes. By
identifying and functionally characterizing apicoplast biogenesis proteins, we will understand how this process
can be disrupted to block pathogenesis in multiple stages of multiple eukaryotic pathogens.

## Key facts

- **NIH application ID:** 10401376
- **Project number:** 5R01AI141366-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ellen Yeh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $584,948
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401376

## Citation

> US National Institutes of Health, RePORTER application 10401376, Harnessing the Unique Biogenesis of the Apicomplexan plastid organelle forAntimalarial Targets (5R01AI141366-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10401376. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*