# Developmental switches regulating tissue cyst formation

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2020 · $546,310

## Abstract

Project Summary
Toxoplasma gondii infections continue to be a public health hazard for millions of individuals that contact this
pathogen annually. More than 50 million individuals in the US are chronically infected with Toxoplasma gondii
and thousands of healthy individuals develop eye disease due to this infection that can lead to permanent
vision loss. The Centers for Disease Control and Prevention considers Toxoplasma one of the five most
important neglected parasitic infections. Individuals can be reasonably treated (despite significant side effects)
if clinical toxoplasmosis is presented, however, there is a lack of drugs to treat or prevent the tissue cyst that is
responsible for long-term infections. This therapy failure leaves at-risk individuals who become infected
vulnerable to disease relapse throughout their lifetimes. Understanding the developmental mechanisms
responsible for tissue cyst formation are needed to develop therapies to combat life-long disease. The
Toxoplasma biology that underlies chronic disease is a reversible transformation of the asexual replicating
tachyzoite into the latent bradyzoite stage. This critical developmental transition is accompanied by significant
changes in gene expression controlled by poorly defined transcriptional mechanisms. Recent experiments of
our group have identified key cell cycle regulated and stress-induced Toxoplasma ApiAP2 factors that prevent
or activate bradyzoite gene expression. We hypothesize these discoveries reveal a transcriptional network
that directs the competing needs of tachyzoite growth against development of the dormant tissue cyst required
for parasite transmission. To understand how this transcriptional network operates, we propose two specific
aims: In Aim 1, the experimental focus will be ApiAP2 transcriptional repressors that are expressed in the
second half of the tachyzoite cell cycle whose mechanisms we will define at the molecular level and
characterize in cell culture and animal models of parasite development. In Aim 2, we will determine how the
stress-induced ApiAP2 repressors and activators compete to control bradyzoite gene expression and
determine how these mechanisms influence Toxoplasma development in the intermediate host.

## Key facts

- **NIH application ID:** 9980272
- **Project number:** 5R01AI124682-04
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Michael W White
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $546,310
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980272

## Citation

> US National Institutes of Health, RePORTER application 9980272, Developmental switches regulating tissue cyst formation (5R01AI124682-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9980272. Licensed CC0.

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