A RESOURCE FOR DEVELOPMENTAL REGULATORY GENOMICS

发育监管基因组学资源

基本信息

批准号：
9922713
负责人：
CHARLES A. ETTENSOHN
金额：
$ 50.26万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9922713
关键词：
ATAC-seq Animals Atlases Automobile Driving Bacterial Artificial Chromosomes Basic Science Biological Models Biology CRISPR/Cas technology Cell Lineage Cells Chromatin Communities Complex Consumption Data Development Developmental Process Dissection Embryo Embryonic Development Engineered Gene Experimental Models Failure Gene Expression Gene Expression Profiling Gene Expression Regulation Gene Silencing Genes Genetic Genetic Diseases Genomics Human Development Human Genetics Institution Laboratories Libraries Maps Measurement Mediating Methods Mission Modeling Molecular Biology Mutation Paper Pathway Analysis Play Process Regulator Genes Reporter Reporter Genes Research Research Personnel Resources Role Sea Urchins Site Speed Standardization Structure System Systems Biology Technology Time Tissue-Specific Gene Expression United States National Institutes of Health base cell type design digital embryo tissue genome-wide instrumentation nano-string network architecture network models new technology programs tool transcription factor vector

项目摘要

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.

发育监管基因组学资源项目概要该提案寻求对发育监管基因组学海胆资源的支持。在过去的5- 10年来，海胆已成为分析空间基因基因组控制的卓越模型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已经在海胆胚胎上得到解决。 GRN 构成基因组序列与转录因子编码表达之间的转换函数基因，在驱动发育过程中发挥着重要作用。因此，目前针对海洋的GRN研究海胆胚胎对于我们理解海胆的所有基因组编码过程具有重要的普遍意义动物发育。该提案基于最近对社区范围内的全面评估为了增强这一研究模型在监管方面的效用，目前最优先开展的活动基因组学。目标包括： a) 扩大重组细菌人工染色体 (BAC) 报告基因的使用用于顺式监管分析（该模型系统的独特焦点）和许多其他应用； b) 创造新的全社区资源，可显着加快和增强 GRN 的分析； c）完善基因扰动技术，以探测 GRN 架构随时间的变化，并提供获得特定细胞类型中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。在总的来说，他们将创建一个目前无法用于任何正在发展的动物系统的工具包，并且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。这与 NIH 使命相关的生物医学意义是双重的。首先，人类发展的失败常见并确定其原因，有必要了解驱动的复杂遗传程序胚胎发育。其次，现在人们普遍认识到，大多数人类遗传病都是由基因表达的错误调节。该项目创建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控制。