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Biomaterials-based Germinal Center Niches for Understanding the B Cell Maturation and B cell receptor signaling

Award Number: R01AI132738
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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PROJECT SUMMARY Antibodies are routinely used as therapeutic agents to fight a wide range of disorders including asthma, blood cancers, breast cancer, arthritis, and transplant rejection. Humoral immunity against infections depends on the germinal center (GC) differentiation process in the B cell follicles of secondary lymphoid organs, such as spleen and lymph nodes. In GCs, B cells rapidly proliferate and somatically mutated high-affinity antibody secreting cells, i.e. plasma cells, are generated from naïve B cells in response to T cell-dependent antigen. To date, the scientific community has relied on animal models to generate high-affinity antibodies and discover fundamental knowledge of GC immunology. Yet scientists are far from understanding the extracellular and intracellular factors that contribute to the exuberant pace of the GC reaction and conversion to antibody secreting cells (ASCs). Recent in vivo studies have uncovered crucial signals such as CD40 ligand (CD40L) from T cells, B cell activation factor from follicular dendritic cells, cytokines, and integrin ligands from the surrounding lymphoid niche, that are required for the induction of GCs and selection of high-affinity cells. Developing biomaterials to recapitulate the process of generating high affinity, antigen specific antibodies ex vivo via the GC process could enable more rapid development of antibodies for use in the treatment of a number of chronic diseases. Such tissue models can also be used to improve the mechanistic investigation into signaling and epigenetic mechanisms that regulate GC B cells. The goal of this study is not to recapitulate all aspects of an in vivo model, but rather to generate a model that will inform the natural process in vivo, and also the development antigen-specific ASCs ex vivo. The specific aims will focus on engineering designer organoids with tunable ligand specificities, understanding the antigen specific immune response, and establish a link between integrin ligand specificity and cell cycle epigenetics of GC reaction.


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: 2023 ( Subtotal = $0 )
2023	2022	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Allergy and Infectious Diseases Research	000	6	3/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $360,056 )
2022	2022	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Allergy and Infectious Diseases Research	000	6	1/19/2022	NON-COMPETING CONTINUATION	$360,056
														Subtotal = $360,056

Issue Date FY: 2021 ( Subtotal = $367,982 )
2021	2021	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Allergy and Infectious Diseases Research	000	5	1/15/2021	NON-COMPETING CONTINUATION	$367,982
2021	2020	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	002	3	7/3/2021	NON-COMPETING CONTINUATION	-$79,379
2021	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Allergy and Infectious Diseases Research	003	4	7/3/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$316,906
2021	2019	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	001	2	7/3/2021	NON-COMPETING CONTINUATION	-$237,527
														Subtotal = $367,982

Issue Date FY: 2020 ( Subtotal = $395,448 )
2020	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	002	4	8/26/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$316,069
2020	2020	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	001	3	8/26/2020	NON-COMPETING CONTINUATION	-$316,069
2020	2020	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	000	3	1/16/2020	NON-COMPETING CONTINUATION	$395,448
														Subtotal = $395,448

Issue Date FY: 2019 ( Subtotal = $394,088 )
2019	2019	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	000	2	1/17/2019	NON-COMPETING CONTINUATION	$394,088
														Subtotal = $394,088

Issue Date FY: 2018 ( Subtotal = $391,799 )
2018	2018	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	000	1	2/8/2018	NEW	$391,799
2018	2018	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	001	1	5/31/2018	NEW	$0
														Subtotal = $391,799

Grand Total All Awards = $1,909,373

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Biomaterials-based Germinal Center Niches for Understanding the B Cell Maturation and B cell receptor signaling

Award Number: R01AI132738

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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