# Development and maintenance of chronic toxoplasmosis

> **NIH NIH R01** · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · 2024 · $642,884

## Abstract

7. PROJECT SUMMARY/ABSTRACT
Chronic Toxoplasma gondii infections are widespread and their reactivation can cause life-threatening disease in
immunocompromised individuals and recurrent ocular lesions in the immunocompetent. The recently identified
master regulator of chronic differentiation, BFD1, provides an unprecedented opportunity to investigate the
molecular events that establish and maintain chronic T. gondii infections. BFD1 is necessary for chronic
differentiation in cell culture and in mouse models of infection, and its expression is sufficient to induce chronic
differentiation. Consistent with a sustained requirement for BFD1 during chronic stage maintenance, the
differentiation program is reversed upon conditional down-regulation of BFD1. Preliminary results indicate that BFD1
is post-transcriptionally controlled through its 5′ UTR, leading to the hypothesis that translational regulation of BFD1
is fundamental to the development and maintenance of chronic T. gondii stages. This proposal seeks to integrate
BFD1 into a broader regulatory network through three complementary aims. Aim 1 will examine the sequence
elements, secondary RNA structures, and ribosomal occupancy dynamics that mediate BFD1 translational
regulation. Aim 2 will use conditional depletion of BFD1 to characterize transcriptional and proteomic changes that
mediate reactivation, and the molecular circuits that maintain the differentiated state. Finally, Aim 3 will extend the
regulatory pathways that control differentiation by screening for genes involved in the translational regulation of BFD1
and further examining the function of transcription factors directly regulated by BFD1. The overarching goal of this
comprehensive analysis is to understand the conditions that promote chronic differentiation and license the
development of curative therapies against toxoplasmosis.

## Key facts

- **NIH application ID:** 10783045
- **Project number:** 5R01AI158501-04
- **Recipient organization:** WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
- **Principal Investigator:** Sebastian Lourido
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $642,884
- **Award type:** 5
- **Project period:** 2021-03-17 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10783045

## Citation

> US National Institutes of Health, RePORTER application 10783045, Development and maintenance of chronic toxoplasmosis (5R01AI158501-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10783045. Licensed CC0.

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