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Development and maintenance of chronic toxoplasmosis

Award Number: R01AI158501
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/17/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Development and maintenance of chronic toxoplasmosis - 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.


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: 2025 ( Subtotal = $607,619 )
2025	2025	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	5	2/18/2025	NON-COMPETING CONTINUATION	$607,619
														Subtotal = $607,619

Issue Date FY: 2024 ( Subtotal = $642,884 )
2024	2024	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	001	4	5/24/2024	NON-COMPETING CONTINUATION	$64,289
2024	2024	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	4	2/22/2024	NON-COMPETING CONTINUATION	$578,595
														Subtotal = $642,884

Issue Date FY: 2023 ( Subtotal = $659,753 )
2023	2023	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	3	2/9/2023	NON-COMPETING CONTINUATION	$659,753
														Subtotal = $659,753

Issue Date FY: 2022 ( Subtotal = $671,297 )
2022	2022	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	2	2/24/2022	NON-COMPETING CONTINUATION	$671,297
														Subtotal = $671,297

Issue Date FY: 2021 ( Subtotal = $682,500 )
2021	2021	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	1	3/17/2021	NEW	$682,500
														Subtotal = $682,500

Grand Total All Awards = $3,264,053

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Development and maintenance of chronic toxoplasmosis

Award Number: R01AI158501

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/17/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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