Regulatory genomics of T cells in mouse and human

项目摘要/摘要 T细胞协调系统免疫，是抵御病毒和细菌感染的关键，而T细胞是免疫系统的重要组成部分。 莫尔斯。我们研究计划的长期目标是利用创新的实验基因组学来构建多个 维度数据资源并开发新的计算方法，我们将使用这些方法来获得全面的 在分子水平上了解T细胞对各种刺激的激活和分化。我们会 解决关于T细胞跨上下文、调节机制对功能命运的承诺的特定fic问题 这些过程及其潜在的转录因子。史无前例的决心和统计能力 使我们能够研究T细胞谱系和亚群之间这些机制的异同， 以及这些观察结果从老鼠到人类的概括性。这一目标将通过执行三个 项目。我们将研究T细胞活化和功能承诺在淋巴细胞脉络膜病变中的调节。 TIS病毒(LCMV)感染模型，重点是祖细胞TCF1+T细胞(项目1)，转录和 Treg细胞的表观遗传调控和高阶染色质组织(项目2)。最后，我们将建立一个 用于跨鼠标比较分析调控基因组数据的数据库、方法、软件和接口 模型和人，允许许多基础和转换应用程序(项目3)。这些研究将 引导未来研究和开发新的治疗性转录因子和其他靶点和调控 T细胞免疫功能紊乱疾病的治疗策略。我们的数据资源和方法将使系统 关于T细胞分子机制的新的特殊fic假说的数据探索、生成和验证 功能，并将提供一个平台，用于映射和分析来自我们和 其他的将在未来产生。

Project Summary/Abstract T cells coordinate systemic immunity and are essential for defense against viral and bacterial infections and tu- mors. The long-term goal of our research program is to employ innovative experimental genomics to build multi- dimensional data resources and develop new computational methods that we will use to obtain a comprehensive understanding at a molecular level of T cell activation and differentiation in response to various stimuli. We will address specific problems about T cell commitment to functional fates across contexts, regulatory mechanisms of these processes and their underlying transcription factors. Unprecedented resolution and statistical power will allow us to study similarities and differences of these mechanisms between T cell lineages and subpopulations, and generalizability of these observations from mouse to human. This goal will be achieved by executing three projects. We will study regulation of T cell activation and functional commitment in lymphocytic choriomeningi- tis virus (LCMV) infection model with a focus on the progenitor TCF1+ T cells (Project 1), transcriptional and epigenetic regulation and higher order chromatin organization in Treg cells (Project 2). Finally, we will build a database, methods, software and interfaces for comparative analysis of regulatory genomics data across mouse models and humans, allowing many fundamental and translational applications (Project 3). These studies will lead to future research and development of new therapeutic transcription factor and other targets and modulation strategies in diseases of dysregulated T cell immunity. Our data resources and methods will enable systematic data exploration, generation and validation of new specific hypotheses about molecular mechanisms of T cell function, and will provide a platform for mapping and analyzing new T cell data from new systems that we and others will generate in the future.