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Leukocyte subset identification by single cell analysis of BTB-ZF gene

Award Number: R21AI095649
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: 01/15/2013
PERIOD OF PERFORMANCE END DATE: 12/31/2014

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Leukocyte subset identification by single cell analysis of BTB-ZF gene - DESCRIPTION (provided by applicant): Numerically minor subsets of lymphocytes have been found to have potent immunomodulatory functions. Indeed, the identification of T cell subsets such as regulatory T cells, T follicular helper cells, natural killer T cells and IL-17 producing T cell have, cumulatively, represented one of the most important advances in understanding the adaptive immune response. BTB-zinc finger (BTB-ZF) transcription factors are defined by an N-terminal protein-protein interaction domain (BTB/POZ) domain, coupled with a C-terminal zinc finger domain. Several members of this BTB-ZF family have emerged as fundamental, non-redundant factors that control the development or function of specific cell types of the immune system. For example, BTB-ZF genes have been shown to control T cell versus B cell commitment (LRF), CD4 versus CD8 lineage commitment (ThPOK), the commitment of thymocytes to innate T cell lineages (PLZF), the development of T follicular helper T cells (Bcl6) as well as differentiation of B cells into germinal center B cells (Bcl6). Additional members of ths gene family clearly influence the immune response, but in less well defined ways. In this R21 application we propose to explore BTB-ZF gene family expression to define novel leukocyte subset effector populations. We will develop a set of BAC-based transgenes that express both GFP and Cre under the control of the regulatory elements for BTB-ZF genes. Preliminary studies suggest that each of the selected BTB-ZF genes is expressed in the immune system, is regulated during development and, potentially, controls the function of a novel subset of cells. We are well positioned to carry out these studies and have already proven that the BAC reporter system is a highly effective approach. Indeed, we would strongly argue that this single cell expression model is essential for identifying leukocyte subsets and for the study of this important new family of transcription factors. The dramatic and nonredundant functions of the BTB-ZF genes that have thus far been identified clearly support the significance of the reagents we propose to develop and evaluate in the context of this R21 application. We believe that this effort will significantly advance the understanding of the transcriptional control of immune responses. Finally, since this family of transcription factors is highly conserved in humans, our studies have the potential to lead to new diagnostic tests and/or therapies.


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: 2014 ( Subtotal = $238,500 )
2014	2014	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	3	12/13/2013	NON-COMPETING CONTINUATION	$214,650
2014	2014	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	003	3	6/5/2014	NON-COMPETING CONTINUATION	$23,850
2014	2013	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	001	2	2/7/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$2,724
2014	2013	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	002	1	2/7/2014	NEW	$2,724
														Subtotal = $238,500

Issue Date FY: 2013 ( Subtotal = $198,126 )
2013	2013	Rutgers, The State Univ Biomedical & HEALTH Sciences	65 Davidson Road	Piscataway	NJ	08554		USA	Allergy and Infectious Diseases Research	003	2	2/7/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$2,724
2013	2013	Rutgers, The State Univ Biomedical & HEALTH Sciences	65 Davidson Road	Piscataway	NJ	08554		USA	Allergy and Infectious Diseases Research	001	2	8/1/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$96,000
2013	2013	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	004	1	2/7/2014	NEW	$2,724
2013	2013	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	1	1/14/2013	NEW	$198,021
2013	2013	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Allergy and Infectious Diseases Research	002	1	8/1/2013	NEW	-$95,895
														Subtotal = $198,126

Grand Total All Awards = $436,626

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Leukocyte subset identification by single cell analysis of BTB-ZF gene

Award Number: R21AI095649

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: 01/15/2013

PERIOD OF PERFORMANCE END DATE: 12/31/2014

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