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Developmental disruption in the transplacental transmission strategy of Toxoplasma gondii

Award Number: F31AI167594
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Developmental disruption in the transplacental transmission strategy of Toxoplasma gondii - Project summary/abstract: Infection-induced developmental divergence in the transplacental transmission strategy of Toxoplasma gondii. Toxoplasma gondii is the world’s most ubiquitous human parasitic infection. Infection of pregnant women can result in transmission of the parasite to the developing fetus, often causing devastating birth defects. Fetal infection requires the parasite to cross the maternal-fetal barrier, a junction primarily defended by the placenta. The strategy by which T. gondii surmounts this tissue barrier is poorly understood at both the cellular and molecular level. Critical to this process are placental trophoblasts, cells that undergo coordinated development into distinct differentiated subtypes (most notably progenitor cytotrophoblasts, CYTs; syncytiotrophoblasts, SYNs; and extravillous trophoblasts; EVTs) to form the maternofetal interface, and which previous data show are differentially susceptible to T. gondii infection. The proposed studies test the hypothesis that T. gondii infection of CYTs alters their developmental trajectory to promote parasite infection in a manner that disrupts proper placental and fetal development. This hypothesis was formulated based on preliminary transcriptome and immunofluorescence data showing that T. gondii-infected CYTs bear gene expression signatures that are more similar to infection-permissive EVTs compared to infection-resistant SYNs. These data suggest that T. gondii- infection alters cell fate to favor one lineage at the cost of the other, possibly to its own advantage. In the proposed studies I will use a bipotent in vitro trophoblast stem cell system and organoid model of placental development to investigate 1) the extent of T. gondii-driven disruption of placental trophoblast development and 2) how this impacts placental trophoblast function.


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: 2024 ( Subtotal = $36,063 )
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	3	5/7/2024	NON-COMPETING CONTINUATION	$36,063
														Subtotal = $36,063

Issue Date FY: 2023 ( Subtotal = $34,783 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	2	3/2/2023	NON-COMPETING CONTINUATION	$34,783
														Subtotal = $34,783

Issue Date FY: 2022 ( Subtotal = $33,841 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	001	1	6/7/2022	NEW	$0
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	002	1	6/9/2022	NEW	$716
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	1	12/2/2021	NEW	$33,125
														Subtotal = $33,841

Grand Total All Awards = $104,687

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Developmental disruption in the transplacental transmission strategy of Toxoplasma gondii

Award Number: F31AI167594

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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