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Modeling the development, structure and regulation of T cell memory

Award Number: R01AI093870
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: 03/01/2011
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Modeling the development, structure and regulation of T cell memory - Project Summary Immunological memory is a defining characteristic of vertebrate immune systems, and is encoded in part by populations of T lymphocytes that respond rapidly and potently to repeat exposures to pathogens. These populations are remarkably diverse in their phenotypes and trafficking patterns, and collectively form an ecosystem that reflects a lifetime's exposure to pathogens and to our environment. Yet a fundamental and pressing problem remains - we have a very limited quantitative grasp of how immunological memory is established and maintained, how new memories to infections are integrated with existing memories, and how and why these wane over time. A detailed understanding of these phenomena would guide the design of vaccines that induce durable immunity, and the development of therapies to revive and sustain T cell responses in the settings of chronic infections and cancer. The memory encoded by circulating T cells is highly dynamic. It is sculpted by self-renewal, differentiation, loss, and supplementation or competition with newly-recruited cells. Further, in both mice and humans, memory induced by pathogens co-exists with abundant 'natural' memory T cells, which are specific for commensal and environmental antigens but provide cross-protection to new infections; and with regulatory T cells, that limit inappropriate responses. We have very little understanding of how these three populations relate. In this project we will integrate together a powerful set of modeling and experimental approaches to confront these uncertainties. Specifically, we will develop a structured population modeling (PDE) approach to use with a fate-mapping system that tracks T cell populations throughout their life-histories. We will then combine the fate mapping system with a DNA labeling method and ODE models to define memory T cell dynamics in detail. Together, these approaches will map the development, structure, and rules of replacement of circulating memory T cell subsets in mice. We will also use data from a novel division-reporter mouse strain to model the emergence and long-term dynamics ofT cell memory to influenza infection. Finally, we will combine modeling with fate-mapping and division-reporter mice to understand how regulatory T cells are maintained, and how they impact both natural and influenza-specific memory populations.


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 = $487,050 )
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	000	16	7/31/2024	NON-COMPETING CONTINUATION	$487,050
														Subtotal = $487,050

Issue Date FY: 2023 ( Subtotal = $487,049 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	001	15	7/14/2023	NON-COMPETING CONTINUATION	$487,050
2023	2020	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	000	12	11/21/2022	NON-COMPETING CONTINUATION	-$1
														Subtotal = $487,049

Issue Date FY: 2022 ( Subtotal = $487,050 )
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	001	14	8/5/2022	NON-COMPETING CONTINUATION	$487,050
2022	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	000	12	5/20/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $487,050

Issue Date FY: 2021 ( Subtotal = $504,481 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	001	13	9/17/2021	COMPETING CONTINUATION	$504,481
2021	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	000	12	9/17/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $504,481

Issue Date FY: 2020 ( Subtotal = $370,574 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	000	12	2/5/2020	NON-COMPETING CONTINUATION	$370,574
														Subtotal = $370,574

Issue Date FY: 2019 ( Subtotal = $370,574 )
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	000	11	2/18/2019	NON-COMPETING CONTINUATION	$370,574
														Subtotal = $370,574

Issue Date FY: 2018 ( Subtotal = $391,883 )
2018	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	002	10	2/27/2018	NON-COMPETING CONTINUATION	$359,710
2018	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	005	9	3/31/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$351,642
2018	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Allergy and Infectious Diseases Research	001	9	1/4/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$170,474
2018	2017	THE UNIVERSITY OF GLASGOW	UNIVERSITY AVENUE	GLASGOW	LANARKSHIRE	G12 8QQ		GBR	Allergy and Infectious Diseases Research	000	8	1/4/2018	NON-COMPETING CONTINUATION	-$138,301
2018	2017	UNIVERSITY OF GLASGOW	DIRECTORATE FINANCE OFFICE	GLASGOW	LANARKSHIRE	G12 8QQ		GBR	Allergy and Infectious Diseases Research	004	8	3/31/2018	NON-COMPETING CONTINUATION	-$179,487
2018	2016	UNIVERSITY OF GLASGOW	DIRECTORATE FINANCE OFFICE	GLASGOW	LANARKSHIRE	G12 8QQ		GBR	Allergy and Infectious Diseases Research	003	7	3/31/2018	COMPETING CONTINUATION	-$172,155
														Subtotal = $391,883

Issue Date FY: 2017 ( Subtotal = $317,788 )
2017	2017	THE UNIVERSITY OF GLASGOW	UNIVERSITY AVENUE	GLASGOW	LANARKSHIRE	G12 8QQ		GBR	Allergy and Infectious Diseases Research	000	8	2/17/2017	NON-COMPETING CONTINUATION	$317,788
														Subtotal = $317,788

Issue Date FY: 2016 ( Subtotal = $323,923 )
2016	2016	THE UNIVERSITY OF GLASGOW	RESEARCH SUPPORT OFFICE	GLASGOW				GBR	Allergy and Infectious Diseases Research	001	7	3/2/2016	COMPETING CONTINUATION	$323,923
2016	2015	THE UNIVERSITY OF GLASGOW	RESEARCH SUPPORT OFFICE	GLASGOW				GBR	Allergy and Infectious Diseases Research	000	6	3/2/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $323,923

Issue Date FY: 2015 ( Subtotal = $269,936 )
2015	2015	THE UNIVERSITY OF GLASGOW	RESEARCH SUPPORT OFFICE	GLASGOW				GBR	Allergy and Infectious Diseases Research	000	6	3/12/2015	NON-COMPETING CONTINUATION	$269,936
														Subtotal = $269,936

Issue Date FY: 2014 ( Subtotal = $295,117 )
2014	2014	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Allergy and Infectious Diseases Research	000	4	2/13/2014	NON-COMPETING CONTINUATION	$356,483
2014	2014	THE UNIVERSITY OF GLASGOW	RESEARCH SUPPORT OFFICE	GLASGOW				GBR	Allergy and Infectious Diseases Research	002	5	9/5/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$157,474
2014	2014	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Allergy and Infectious Diseases Research	001	4	9/4/2014	NON-COMPETING CONTINUATION	-$218,840
														Subtotal = $295,117

Issue Date FY: 2013 ( Subtotal = $336,696 )
2013	2013	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Allergy and Infectious Diseases Research	001	3	5/29/2013	NON-COMPETING CONTINUATION	$14,328
2013	2013	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Allergy and Infectious Diseases Research	000	3	2/27/2013	NON-COMPETING CONTINUATION	$322,368
														Subtotal = $336,696

Issue Date FY: 2012 ( Subtotal = $359,842 )
2012	2012	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Allergy and Infectious Diseases Research	000	2	2/16/2012	NON-COMPETING CONTINUATION	$359,842
														Subtotal = $359,842

Issue Date FY: 2011 ( Subtotal = $377,948 )
2011	2011	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Allergy and Infectious Diseases Research	000	1	2/18/2011	NEW	$377,948
														Subtotal = $377,948

Grand Total All Awards = $5,379,911

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Modeling the development, structure and regulation of T cell memory

Award Number: R01AI093870

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: 03/01/2011

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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