A RESOURCE FOR DEVELOPMENTAL REGULATORY GENOMICS

生殖调控基因组学资源 项目摘要 该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- 10年来，海胆已成为分析基因组控制空间基因的卓越模型 在胚胎发育过程中表达。最完整的基因调控网络（GRNs） 我们对任何动物的发展最近已经解决了海胆胚胎。GRN构成 基因组序列与转录因子编码基因表达之间的转换功能 基因，在驱动发育过程中发挥着重要作用。因此，目前对海洋的GRN研究 海胆胚胎对我们理解所有基因组编码的过程具有重要的普遍意义， 动物发展。这项建议是基于最近一项全面的社区评估， 这些活动现在是最优先的，以提高这一研究模式的效用， 基因组学目的包括：a）扩大重组细菌人工染色体（BAC）报告基因的使用 用于顺式调节分析（该模型系统的独特焦点）和用于许多其他应用; B）创建 新的社区范围的资源，以显着加快和加强对GRN的分析;以及c） 基因扰动技术的改进，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先前难以处理的基因调控相互作用。每一个目标 利用（并扩展）海胆的实验优势，用于调节系统生物学。在 总的来说，他们将创造一个工具包，目前还没有为任何发展中的动物系统，并将有一个 对从事发育调控生物学的研究人员群体产生了巨大影响。的 与NIH使命相关的生物医学意义是双重的。首先，人类发展的失败是 为了确定它们的原因，了解驱动这些疾病的复杂遗传程序是至关重要的。 胚胎发育。第二，现在人们普遍认识到，大多数人类遗传疾病是由于 基因表达的错误调节。该项目创造的资源将刺激基础研究， 帮助我们更好地理解动物细胞中基因表达的控制。

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.