The objectives of the research proposals in this application are to determine at a global scale the mechanisms that underpin the ?? versus ?? lineage choice. Many of the experiments proposed in the application involve genome-wide analyses and interpretation of the data obtained from such analyses. The purpose of the Genomics Core is to provide the laboratories with the following services that will permit the proposed studies to be completed. The Genomics Core would perform HiC, ChlP-Seq and RNA-Seq analyses, followed by bioinformatics analysis. Thus the entire spectrum of genome-wide analyses that concerns this POl would be performed at the UCSD Genomics Core Facility. Why a centralized Genomics Core? There are three reasons: (1) Except for the Murre laboratory, none of the participating laboratories have expertise in ChlP-Seq and RNA-Seq. (2) The Zhuang, Wiest and Zuniga-Pflucker laboratories do not have access to the bioinformatic infrastructure and analytical tools that have been established at UCSD. (3) The genomics core would permit us to standardize the ChlP-Seq and RNA-Seq analysis. This means using the same antibodies, same lot number and the same approach thereby allowing a careful and consistent comparison of the different binding patterns that will be derived from the various studies. (4) The Genomics Core will provide training to visiting research fellows. Thus, we envision that graduate students and postdoctoral fellows from the other laboratories would visit UCSD in order to become familiar with global approaches and analyses. Accordingly, an integral part of our approach is to provide personnel from different institutions access to these global analysis tools and provide training.

Public Health Relevance

It has been established that an important population of cells, named ?? T cells, play critical roles in preserving epithelial structures that function as barriers. The proposal described here is aimed to understand the molecular mechanisms that promote their developmental progression. These studies may permit novel avenues for the treatment of immune diseases and interference with the development of malignancies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI102853-04
Application #
9260754
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Research Institute of Fox Chase Cancer Center
Department
Type
DUNS #
064367329
City
Philadelphia
State
PA
Country
United States
Zip Code
19111
Fahl, Shawn P; Coffey, Francis; Kain, Lisa et al. (2018) Role of a selecting ligand in shaping the murine ??-TCR repertoire. Proc Natl Acad Sci U S A 115:1889-1894
Zarin, Payam; In, Tracy Sh; Chen, Edward Ly et al. (2018) Integration of T-cell receptor, Notch and cytokine signals programs mouse ?? T-cell effector differentiation. Immunol Cell Biol 96:994-1007
Zhang, Baojun; Jiao, Anjun; Dai, Meifang et al. (2018) Id3 Restricts ?? NKT Cell Expansion by Controlling Egr2 and c-Myc Activity. J Immunol 201:1452-1459
Murre, Cornelis (2018) 'Big bang' of B-cell development revealed. Genes Dev 32:93-95
Roy, Sumedha; Moore, Amanda J; Love, Cassandra et al. (2018) Id Proteins Suppress E2A-Driven Invariant Natural Killer T Cell Development prior to TCR Selection. Front Immunol 9:42
Chisolm, Danielle A; Savic, Daniel; Moore, Amanda J et al. (2017) CCCTC-Binding Factor Translates Interleukin 2- and ?-Ketoglutarate-Sensitive Metabolic Changes in T Cells into Context-Dependent Gene Programs. Immunity 47:251-267.e7
Li, Jia; Roy, Sumedha; Kim, Young-Mi et al. (2017) Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors. J Immunol 198:3136-3148
Zhu, Yina; Gong, Ke; Denholtz, Matthew et al. (2017) Comprehensive characterization of neutrophil genome topology. Genes Dev 31:141-153
Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Kenian et al. (2017) The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development. Immunity 46:818-834.e4
Moore, Amanda J; In, Tracy Sh; Trotman-Grant, Ashton et al. (2017) A key role for IL-7R in the generation of microenvironments required for thymic dendritic cells. Immunol Cell Biol 95:933-942

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