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CONTROL OF T CELL SYNAPSE STABILIZATION AND SIGNALING

Award Number: R37AI052116
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: 09/15/2002
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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CONTROL OF T CELL SYNAPSE STABILIZATION AND SIGNALING - PROJECT SUMMARY How do T cells find and their targets? Thanks to studies using high abundance, high affinity agonists and antibodies, many of the signaling pathways downstream from TCR engagement – through lck, ZAP-70, LAT, and further adapters and transcription factors – are described. Decades of structural analyses have also revealed the critical residues for ligand binding. Yet, as we have attempted to make T cells more tuneable and use them as cellular therapies, it is evident that we still cannot create a T cell that has all the features—sensitivity, specificity, effector functions—that we want in order to achieve clinical efficacy. Receptors reside on cell membranes. Cell membranes move and bend and provide 3D surfaces on which receptors can transit, both individually and in patches. We hypothesize that the relationship of T cell receptors to their underlying membrane is critical for determining their function. This proposal will study the effect of the subsurface domain distribution of receptors, achieved through engineering of T cells (Aim 1), engineering of surrogate ligands and cells (Aim 2) and through adoption of cell- cell fusogens that alter the immediate sequellae of membrane-membrane apposition (Aim 3). In all cases, we will be studying the output across a range of measures, starting by studying the 3D distribution of engineered receptors over time, moving to studying the effect of the perturbation on activation measures, and finally assessing these modification in models of human disease. The results of these studies will provide us with critical information about the interacting nature of receptors and membranes as they influence T cell activation.


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 = $712,171 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	22	1/8/2025	SUPPLEMENT FOR EXPANSION	$50,417
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	002	22	7/11/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	004	23	7/29/2025	SUPPLEMENT FOR EXPANSION	$86,428
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	22	6/12/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	003	23	7/14/2025	NON-COMPETING CONTINUATION	$575,326
														Subtotal = $712,171

Issue Date FY: 2024 ( Subtotal = $575,229 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	22	7/31/2024	NON-COMPETING CONTINUATION	$575,229
														Subtotal = $575,229

Issue Date FY: 2023 ( Subtotal = $575,132 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	21	7/31/2023	COMPETING CONTINUATION	$575,132
														Subtotal = $575,132

Grand Total All Awards = $1,862,532

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CONTROL OF T CELL SYNAPSE STABILIZATION AND SIGNALING

Award Number: R37AI052116

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: 09/15/2002

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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