San Diego Center for 4D Nucleome Research

圣地亚哥 4D 核组研究中心

基本信息

批准号：
9353380
负责人：
CORNELIS MURRE
金额：
$ 179.16万
依托单位：
LUDWIG INSTITUTE FOR CANCER RES LTD
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9353380
关键词：
3-Dimensional Architecture Base Sequence Binding Biochemical Biological Assay Biology Cell Count Cell Nucleus Cells Chromatin Chromatin Loop Chromatin Structure Collaborations Color Communities DNA DNA biosynthesis Data Data Set Development Enhancers Environment Gene Expression Gene Expression Regulation Genetic Genetic Transcription Genome Genome Mappings Genomics Goals Gold Group Meetings High-Throughput DNA Sequencing Human Human Genome Imaging technology Influentials Investigation Joints Knowledge Light Mammalian Cell Mammalian Chromosomes Maps Measures Methodology Methods Microscopy Modeling Molecular Motion Mus Nuclear Nuclear Structure Performance Physics Play Principal Investigator Process Protocols documentation Publications Reagent Records Regulator Genes Regulatory Element Research Research Activity Research Personnel Resolution Role Sampling Scientist Software Tools Structure Technology Teleconferences Time Transcriptional Regulation United States National Institutes of Health Vision analytical method analytical tool base cell type computer framework data sharing epigenome experience genetic information genome-wide genome-wide analysis human disease human genome sequencing imaging approach improved in vivo innovation insight live cell imaging mammalian genome member next generation novel programs promoter public health relevance symposium tool transcriptome working group

项目摘要

DESCRIPTION: The complete sequencing of the human genome has provided an unprecedented opportunity for the study of the structure and function of the human genome. While our genome has historically been viewed as a linear sequence of bases, it has progressively become clear that this is an inadequate way to represent our genetic information. Notably, research over the last 30 years has begun to shed light on the fact that the higher-order, 3-dimensional organization of our genome plays a critical role in the interpretation of the genetic information encoded in our genome. The structure of our genome in the nucleus has been clearly demonstrated to play influential roles in diverse nuclear processes including DNA replication and gene expression. Despite this, our understanding of the structure of our genome within the nucleus remains incomplete. The reasons for this include limitations in the resolution and throughput of existing tools in chromatin topology mapping, a scarcity of the analytical tools for studying genome structure datasets, and the difficulty to relate the nuclear structure to function. Due to recent advancements in molecular methods based on high-throughput DNA sequencing, single cell analytical approaches, and high-resolution microscopy, the time for breaking through these previous limitations has come. We will establish a highly collaborative, innovative team in order to develop the tools necessary to transform our understanding of chromatin architecture and function in mammalian cells. We will begin by developing datasets that establish gold standards for the study of nuclear structure and function using genetic, biochemical and imaging approaches. We will optimize current existing technologies for mapping genome wide chromatin interactions, while also developing novel, complementary approaches for studying chromatin structure. We will also develop innovative analytical methods to interpret the chromatin structural data, unraveling principles of structural- and temporal- chromatin organization. Our highly collaborative team will draw on the diverse experiences of its members to provide a synergistic environment to push the limits of our understanding of nuclear structure. We expect that the tools and datasets generated through the proposed research will dramatically advance our understanding of the chromatin structure and function in human cells.

描述：人类基因组的完整测序为研究人类基因组的结构和功能提供了前所未有的机会。尽管我们的基因组历史上一直被视为碱基的线性序列，但逐渐清楚地表明，这是代表我们遗传信息的一种不足的方法。值得注意的是，在过去的30年中，研究开始揭示了以下事实：我们基因组的高阶，三维组织在解释我们基因组中编码的遗传信息的解释中起着关键作用。已经清楚地证明了我们基因组在细胞核中的结构在包括DNA复制和基因表达在内的潜水核过程中起影响作用。尽管如此，我们对细胞核内基因组结构的理解仍然不完整。其原因包括染色质拓扑映射中现有工具的分辨率和吞吐量的局限性，用于研究基因组结构数据集的分析工具的稀缺性以及将核结构与功能相关的困难。由于基于高通量DNA测序，单细胞分析方法和高分辨率显微镜的分子方法的最新进展，因此出现了这些先前局限性的时间。我们将建立一个高度协作，创新的团队，以开发改变我们对哺乳动物细胞中染色质体系结构和功能的理解所需的工具。我们将首先开发使用遗传，生化和成像方法来研究核结构和功能的黄金标准的数据集。我们将优化当前的现有技术来绘制基因组广泛的染色质相互作用，同时还开发了研究染色质结构的新颖，完整的方法。我们还将开发创新的分析方法来解释染色质结构数据，并揭示结构和临时染色质组织的原理。我们高度合作的团队将借鉴其成员的不同经验，以提供一个协同的环境，以推动我们对核结构的理解的局限性。我们希望通过拟议的研究生成的工具和数据集将极大地提高我们对人类细胞中染色质结构和功能的理解。