Administrative Core

行政核心

• 批准号: 8608280
• 负责人: DAVID L. WIEST
• 金额: $ 10.47万
• 依托单位: RESEARCH INST OF FOX CHASE CAN CTR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8608280
• 关键词: Address; Adopted; Adoption; Binding Sites; Bioinformatics; Biology; Boxing; California; Cells; ChIP-seq; Collaborations; Communities; Complex; Coupled; Cues; DNA-Binding Proteins; Data; Decision Making; Dependence; Development; Disputes; Ensure; Family; Fostering; Funding; Generations; Genes; Genomics; Goals; Human Resources; Individual; Information Distribution; Institution; Laboratories; Ligands; Lymphocyte Function; Methodology; Molecular; National Institute of Allergy and Infectious Disease; Pathway interactions; Preparation; Process; Production; Progress Reports; Protein Binding; Reagent; Receptor Signaling; Reporting; Research; Research Activity; Research Infrastructure; Research Priority; Resolution; Role; Sampling; Scientist; Services; Site; Specific qualifier value; Structure; T-Cell Development; T-Cell Receptor; T-Lymphocyte; Teleconferences; Therapeutic; Training; Transcriptional Regulation; Travel; Universities; Visit; base; biological research; cellular targeting; conflict resolution; cytokine; extracellular; genome-wide analysis; insight; meetings; member; mouse model; notch protein; novel; progenitor; programs; protein function; receptor expression; research study; skills; success; symposium; tool

The primary role of the Administrative Core is to coordinate research activities among the 4 Project Sites and Genomics Core. Biological research is moving beyond the analysis of single genes or pathways. Accordingly, this program seeks to iise genome-wide analysis to gain insight into the way that differences in T cell receptor (TCR) signal strength direct thymic progenitors to adopt the γδ fate and select an effector function. To do so, we will employ genomic analysis focused on the cellular targets of E box DNA-binding proteins (E proteins), which regulate critical checkpoints in development of αβ and γδ T cells. Genomic analysis of E protein binding sites will be coupled with novel bioinformatic tools to identify cooperating DNA-binding proteins and assemble this information into global regulatory networks defining key milestones in γδ development. The program integrates the efforts of four leaders in γδ T cell development and E protein function. Project 1 will explore the role of ligands in enabling different γδ TCR complexes to promote the adoption of distinct developmental fates. Project 2 will assess the interplay between E proteins and their Id family antagonists in regulating fate choices through actions prior to TCR expression. Project 3 will evaluate the cooperation of extracellular cues (TCR, Notch and cytokines) in, specifying γδ effector fate. Finally, Project 4 will establish comprehensive networks defining distinctions between αβ and γδ lineage commitment and their dependence on Id antagonists. These networks will serve as a framework within which the networks generated in Projects 1-3 will be interpreted. Network construction for all projects will be performed at the Genomics Core, which will also serve to instruct trainees from each program in genomic analysis. The Administrative Core will coordinate these activities by: 1) establishing a management structure; 2) facilitating the distribution of reagents; and 3) coordinating scientific interchanges between project sites and trainee visits to the Genomics Core. Collectively, our program promises not only to reveal novel insights into the molecular control of γδ T cell development, but will also equip a new cadre of scientists with the skills to apply integrated wet bench and bioinformatic approaches to important questions in biology.

行政核心的主要作用是协调4个项目之间的研究活动 网站和基因组学核心。生物学研究正在超越单个基因的分析， 途径。因此，该计划旨在使全基因组分析深入了解 T细胞受体（TCR）信号强度的差异指导胸腺祖细胞采用γδ命运并选择 效应器功能。为此，我们将采用基因组分析，重点是E盒的细胞靶点 DNA结合蛋白（E蛋白），调节αβ和γδ T细胞发育中的关键检查点。 E蛋白结合位点的基因组分析将与新的生物信息学工具相结合， 合作的DNA结合蛋白，并将这些信息组装成全球调控网络， γδ发展的重要里程碑。该计划整合了γδ T细胞领域四位领导者的努力， 发育和E蛋白功能。项目1将探索配体在使不同的γδ TCR 复合物，以促进通过不同的发展命运。项目2将评估 E蛋白及其Id家族拮抗剂通过先于TCR的作用调节命运选择 表情项目3将评估细胞外因子（TCR，Notch和细胞因子）在以下方面的合作， 指定γδ效应子命运。最后，项目4将建立全面的网络， αβ和γδ谱系定型与它们对Id拮抗剂的依赖性之间的关系。这些网络将 作为一个框架，在项目1-3中产生的网络将被解释。网络 所有项目的建设将在基因组学核心进行，这也将有助于指导 每个项目的受训人员都在基因组分析中。行政核心将协调这些活动 通过：1）建立管理结构; 2）促进试剂的分配; 3）协调 项目地点之间的科学交流和实习生对基因组学核心的访问。总体而言，我们 该计划不仅有望揭示γδ T细胞发育的分子控制的新见解， 还将为新的科学家队伍提供应用综合湿台和生物信息学的技能， 研究生物学中重要问题的方法。