A RESOURCE FOR DEVELOPMENTAL REGULATORY GENOMICS

发育调控基因组学资源 项目总结 这项提案寻求对发育调控基因组学海胆资源的支持。在过去的5年里- 10年来，海胆已经成为分析空间基因基因组控制的卓越模型 在胚胎发育过程中的表达。最完整的基因调控网络(GRN) 我们对任何动物的发育最近都解决了海胆胚胎的问题。GRN构成 基因组序列与转录因子编码表达之间的转换功能 基因，它们在推动发育过程中发挥着关键作用。因此，目前对海洋GRN的研究 海胆胚胎对于我们理解所有的基因编码过程具有重要的普遍意义。 动物发育。这项建议是基于最近一项全面的、全社会范围的评估 目前最优先的活动，以加强这一研究模式对监管的效用 基因组学。目的包括：a)扩大重组细菌人工染色体(BAC)记者的使用 用于顺式监管分析(本模式系统的一个独特重点)和许多其他应用；b)创建 提供新的社区资源，以大大加快和加强对GRN的分析；以及c) 改进基因扰动技术以探测GRN结构随时间的变化并提供 在特定细胞类型中获得以前难以处理的基因调控相互作用。这些目标中的每一个 利用(并扩展)海胆在调节系统生物学方面的实验优势。在 总而言之，他们将创建一个目前无法用于任何开发中的动物系统的工具包，并将拥有一个 对从事发育调控生物学的研究人员群体产生了巨大的影响。这个 与NIH任务相关的生物医学影响是双重的。首先，人类发展的失败是 要找出它们的共同之处并找出它们的原因，就必须了解驱动它们的复杂遗传程序 胚胎发育。其次，现在人们普遍认为，大多数人类遗传病都是由 基因表达的错误调控。该项目创造的资源将刺激基础研究， 帮助我们更好地了解动物细胞中基因表达的调控。

A RESOURCE FOR DEVELOPMENTAL REGULATORY GENOMICS PROJECT SUMMARY This proposal seeks support for a sea urchin Resource for Developmental Regulatory Genomics. In the past 5- 10 years, the sea urchin has become a pre-eminent model for analysis of the genomic control of spatial gene expression during embryonic development. The most complete gene regulatory networks (GRNs) for development that we have for any animal have recently been solved for sea urchin embryos. GRNs constitute the transformation function between the genomic sequence and the expression of transcription factor-encoding genes, which play a cardinal role in driving developmental processes. Therefore, current GRN research on sea urchin embryos has great general significance for our understanding of all genomically encoded processes of animal development. The proposal is founded on a recent, comprehensive, community-wide assessment of activities that are now of the highest priority in order to enhance the utility of this research model for regulatory genomics. The aims include: a) expanded use of recombineered, bacterial artificial chromosome (BAC) reporters for cis-regulatory analysis (a unique focus of this model system) and for many other applications; b) the creation of new community-wide resources to dramatically speed and enhance the analysis of GRNs; and c) the refinement of gene perturbation technologies to probe changes in GRN architecture over time and to provide access to previously intractable gene regulatory interactions in specific cell types. Every one of these aims capitalizes on (and extends) the experimental advantages of sea urchins for regulatory systems biology. In the aggregate, they will create a tool kit currently not available for ANY developing animal system and will have a dramatic impact on the community of researchers engaged in the regulatory biology of development. The biomedical implications relevant to the NIH mission are twofold. First, failures of human development are common and to identify their causes it will be essential to understand the complex genetic programs that drive embryonic development. Second, it is now widely recognized that most human genetic diseases are a result of the mis-regulation of gene expression. The resources created by this project will spur basic research that will help us to better understand the control of gene expression in animal cells.