# Epitranscriptomics in the AIDS-opportunistic pathogen Toxoplasma gondii

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $232,760

## Abstract

Toxoplasma gondii is an intracellular parasite that has infected up to one-third of the population. The pathogen
can cause congenital birth defects and life-threatening opportunistic infection in HIV/AIDS. The replicative
stage (tachyzoite) develops into a latent stage (bradyzoite) that resides inside brain, heart, and skeletal muscle
tissues, and is impervious to immunity and currently approved antiparasitic drugs. Tissue cysts give rise to
recurrent reactivation of infection in immunocompromised patients, creating chronic disease in HIV/AIDS
patients. Despite its clinical importance, we know very little about the molecular details orchestrating the
conversion between tachyzoites and bradyzoites. Studies have revealed that the development of bradyzoites,
which can be triggered in vitro by cellular stress, is a complex process subject to regulation at transcriptional
and post-transcriptional levels. Recently, it has been shown in other species that mRNA modifications,
specifically post-transcriptional methylation of adenosines at position 6 (m6A), influence gene expression by
altering RNA processing or translation. Changes in m6A marks have been associated with modulating cellular
stress, development, and differentiation. The discovery of m6A represents a new layer of gene regulation
called epitranscriptomics that has not been investigated in protozoan parasites. In preliminary studies, we
establish that Toxoplasma RNA is subject to m6A, and we have begun characterizing the enzyme complex that
delivers this RNA modification. The study of m6A in Toxoplasma in the context of HIV/AIDS is significant as
this modification has been linked to stress-induced changes in cells, making it highly likely that m6A
participates in bradyzoite development. In this new R21, we will address our hypothesis that m6A mRNA
modifications are required for tachyzoite differentiation into bradyzoites by identifying changes in the m6A
epitranscriptome during stage conversion (Aim 1) and determining the “writer” protein complex that delivers
m6A onto Toxoplasma mRNA (Aim 2). Our proposed studies will be the first analysis of m6A on mRNA in
parasites, and will generate valuable datasets and reagents needed to interrogate this vital new area of
investigation relevant to the development of the tissue cysts, which give rise to chronic toxoplasmosis in
HIV/AIDS patients.

## Key facts

- **NIH application ID:** 9889878
- **Project number:** 5R21AI145239-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** William J Sullivan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $232,760
- **Award type:** 5
- **Project period:** 2019-03-08 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889878

## Citation

> US National Institutes of Health, RePORTER application 9889878, Epitranscriptomics in the AIDS-opportunistic pathogen Toxoplasma gondii (5R21AI145239-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9889878. Licensed CC0.

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