San Diego Center for 4D Nucleome Research

 产品说明：人类基因组测序的完成为人类基因组结构和功能的研究提供了前所未有的机遇。虽然我们的基因组在历史上一直被视为线性碱基序列，但越来越清楚的是，这并不足以代表我们的遗传信息。值得注意的是，过去30年的研究已经开始揭示这样一个事实，即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方面起着关键作用。我们的基因组在细胞核中的结构已被清楚地证明在包括DNA复制和基因表达在内的各种核过程中发挥着重要作用。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图中现有工具的分辨率和吞吐量的限制，用于研究基因组结构数据集的分析工具的稀缺性，以及难以将核结构与功能联系起来。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，突破这些先前限制的时间已经到来。我们将建立一个高度协作，创新的团队，以开发必要的工具，以改变我们对哺乳动物细胞染色质结构和功能的理解。我们将开始开发数据集，建立金标准的核结构和功能的研究，使用遗传，生物化学和成像方法。我们将优化目前现有的绘制全基因组染色质相互作用的技术，同时也开发新的，互补的方法来研究染色质结构。我们还将开发创新的分析方法来解释染色质结构数据，揭示结构和时间染色质组织的原则。我们高度合作的团队将利用其成员的不同经验，提供一个协同的环境，以推动我们对核结构的理解的极限。我们希望通过拟议的研究产生的工具和数据集将大大提高我们对人类细胞中染色质结构和功能的理解。

 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.