Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Investigating differentiation, maintenance, and reactivation of the Toxoplasma chronic stage

Award Number: F32AI181510
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2024
PERIOD OF PERFORMANCE END DATE: 11/30/2025
AWARD TERMINATION DATE: 01/15/2026

Group Awards By:

View Award Description

Investigating differentiation, maintenance, and reactivation of the Toxoplasma chronic stage - 7. PROJECT SUMMARY/ABSTRACT Toxoplasma gondii is one of the most ubiquitous parasites of humans, chronically infecting one quarter of the world’s population. Though typically asymptomatic in immunocompetent hosts, infection can give rise to severe clinical complications in the immunocompromised or during periods of weakened immune function. Parasites that maintain the chronic infection are transcriptionally distinct from the acute stages that cause pathology, and are resistant to treatment with antiparasitics. Understanding regulation of the T. gondii chronic stage is therefore necessary to prevent and eradicate persistent reservoirs of disease. Our lab recently identified two core components of the chronic differentiation program. First, we found that a single transcription factor, BFD1, is necessary and sufficient for stage conversion. More recently, I discovered a cytosolic RNA-binding protein (BFD2) that functions immediately upstream of BFD1 to regulate its expression. Parasites lacking either factor are not able to produce chronic stages, either in mice or in response to alkaline stress—a standard in vitro trigger of differentiation. My work suggests that BFD2 functions as a translational activator of BFD1 under stress, and that this requires binding of BFD2 to BFD1 mRNA. In turn, BFD1 promotes BFD2 transcription, outlining a feedback loop. This reciprocal positive regulation provides the driving force to commit parasites to their chronic differentiation program; yet, precisely how the BFD1-BFD2 circuit is triggered by stress, and later overturned during reactivation, remains to be explored. In the proposed studies, I will uncover the molecular basis of BFD2 regulation through three complimentary aims. Aim 1 will investigate the mechanism of translational activation by BFD2, and how this is influenced by protein-protein interactions. Aim 2 will assess the role of post-translational modification in licensing stress-responsive BFD2 activity. Aim 3 will employ a novel gain-of-function screening approach to identify the factors responsible for antagonizing the BFD1-BFD2 circuit during chronic-stage reactivation. Together, these studies will integrate the genetic mechanisms underlying entry and exit from the T. gondii chronic stage with the signals that trigger stage conversion, which may inform the design of therapies to combat this important human pathogen.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$22,608 )
2026	2025	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	2	1/15/2026	TERMINATION	-$22,608
														Subtotal = -$22,608

Issue Date FY: 2025 ( Subtotal = $80,224 )
2025	2025	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	2	4/18/2025	NON-COMPETING CONTINUATION	$78,892
2025	2025	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	001	2	7/31/2025	NON-COMPETING CONTINUATION	$1,332
														Subtotal = $80,224

Issue Date FY: 2024 ( Subtotal = $76,756 )
2024	2024	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	1	11/28/2023	NEW	$71,792
2024	2024	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	001	1	11/28/2023	NEW	$0
2024	2024	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	002	1	5/8/2024	NEW	$4,964
														Subtotal = $76,756

Grand Total All Awards = $134,372

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating differentiation, maintenance, and reactivation of the Toxoplasma chronic stage

Award Number: F32AI181510

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2024

PERIOD OF PERFORMANCE END DATE: 11/30/2025

AWARD TERMINATION DATE: 01/15/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer