# Determinants of apicoplast maintenance in malaria parasites

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $478,500

## Abstract

Malaria parasites contain a plastid organelle called the apicoplast that is required for parasite survival in
humans and for transmission to mosquitoes. The apicoplast has long been recognized as an important source
of new drug targets to combat the inevitable problem of drug resistance, however, it has proven difficult to
identify and validate apicoplast proteins that are essential for parasite survival. This goal is now achievable
using new genetic tools in combination with metabolic bypass of the apicoplast. Blood stage parasites treated
with the isoprenoid precursor IPP (isopentenyl pyrophosphate) survive apicoplast inhibitors - even those which
result in disruption of the organelle and loss of the organellar genome. We built on this finding by creating a
metabolic bypass parasite line that produces isoprenoid precursors in the cytosol using an engineered four-
enzyme mevalonate pathway. We propose to use a combination of genetic approaches in conjunction with
metabolic bypass to identify all nuclear-encoded proteins which are essential for apicoplast function and
parasite survival. We will also use new conditional tools (knockdown, conditional localization, DiCre) to further
characterize the roles of specific proteins and the phenotypes associated with their loss. Our experiments will
help to build a more complete picture of the metabolic pathways and non-metabolic processes required for
apicoplast function and parasite survival. Ultimately, we intend to identify novel targets and to validate known
targets for future development of drugs to cure malaria and stop its transmission.

## Key facts

- **NIH application ID:** 10840877
- **Project number:** 5R01AI125534-07
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Sean Taylor PRIGGE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $478,500
- **Award type:** 5
- **Project period:** 2016-05-20 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840877

## Citation

> US National Institutes of Health, RePORTER application 10840877, Determinants of apicoplast maintenance in malaria parasites (5R01AI125534-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10840877. Licensed CC0.

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