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Cis-regulatory mechanisms governing RORgt expression in type 3 lymphocytes

Award Number: F31AI181082
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Cis-regulatory mechanisms governing RORgt expression in type 3 lymphocytes - ABSTRACT Type 3 lymphocytes include group 3 innate lymphoid cells (ILC3), IL-17-producing γδ T cells (Tγδ17), and T helper 17 ( TH17) cells and are crucial for maintaining mucosal barrier defenses against extracellular bacteria and fungi. Nonetheless, dysregulated type 3 lymphocyte responses have been implicated in the pathogenesis of several autoimmune diseases, such as inflammatory bowel disease, Crohn's disease, and multiple sclerosis. ILC3, Tγδ17, and TH17 cells are defined by their shared expression of the lineage-defining transcription factor RORγt (Rorc(t)), which facilitates key inductive events during the development and differentiation of these cell types towards the type 3 lymphocyte lineage. The trans-acting factor networks that cooperatively regulate the formation of the type 3 lymphocyte cell types have been well characterized, however, the cis-regulatory elements (CREs) that control the development and differentiation of type 3 lymphocytes remain less defined Therefore, we are proposing a comprehensive assessment of the CREs controlling the expression of the Rorc(t) locus across the type 3 lymphocyte lineage cell types. To this end, we will (i) identify the CREs governing Rorc(t) expression using a high-throughput CRISPRi knockdown screen; (ii) evaluate the activity of Rorc(t) CREs using a retroviral massively parallel STARR-seq reporter assay; (iii) and determine the functional role of putative CREs for the expression of Rorc(t) in the ILC3, Tγδ17, and TH17 cell types. Altogether, the experiments outlined in this proposal will expand our understanding of the cis-regulatory mechanisms governing type 3 lymphocyte development and identity.


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 = $50,114 )
2026	2026	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	001	3	4/1/2026	NON-COMPETING CONTINUATION	$576
2026	2026	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	3	1/29/2026	NON-COMPETING CONTINUATION	$49,538
														Subtotal = $50,114

Issue Date FY: 2025 ( Subtotal = $49,538 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	2	1/14/2025	NON-COMPETING CONTINUATION	$48,974
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	001	2	7/29/2025	NON-COMPETING CONTINUATION	$564
														Subtotal = $49,538

Issue Date FY: 2024 ( Subtotal = $48,974 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	001	1	11/27/2023	NEW	$0
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	003	1	5/8/2024	NEW	$1,280
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	002	1	2/23/2024	NEW	$0
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	1	11/27/2023	NEW	$47,694
														Subtotal = $48,974

Grand Total All Awards = $148,626

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Cis-regulatory mechanisms governing RORgt expression in type 3 lymphocytes

Award Number: F31AI181082

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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