Administrative Core

行政核心

基本信息

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
项目类别：
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

项目摘要

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位点和基因组学核心生物学研究正在超越单个基因或基因的分析。因此，该计划旨在进行全基因组分析，以深入了解这一过程。 T细胞受体（TCR）信号强度的差异指导胸腺祖细胞采用γδ命运并选择为此，我们将采用针对 E 盒细胞靶标的基因组分析。 DNA 结合蛋白（E 蛋白），调节 αβ 和 γδ T 细胞发育过程中的关键检查点。 E 蛋白结合位点的基因组分析将与新型生物信息学工具相结合，以识别合作DNA结合蛋白并将这些信息组装到全球监管网络中定义该计划整合了 γδ T 细胞领域四位领导者的努力。项目 1 将探索配体在实现不同 γδ TCR 中的作用。项目 2 将评估这种相互作用。 E蛋白及其Id家族拮抗剂之间通过TCR之前的作用调节命运选择项目 3 将评估细胞外信号（TCR、Notch 和细胞因子）的合作，最后，项目 4 将建立定义差异的综合网络。 αβ 和 γδ 谱系承诺及其对 Id 拮抗剂的依赖之间的关系。作为一个框架，项目 1-3 中生成的网络将在其中进行解释。所有项目的建设都将在基因组核心进行，该核心也将用于指导每个基因组分析项目的学员将协调这些活动。通过： 1) 建立管理结构； 2) 促进试剂的分配；以及 3) 协调；项目地点之间的科学交流和学员参观基因组学核心。该计划不仅有望揭示 γδ T 细胞发育的分子控制的新见解，而且还将为新的科学家队伍配备应用综合湿台和生物信息学的技能生物学中重要问题的方法。