GLOBAL GENE REGULATORY NETWORKS FOR SPECIFIC CELL TYPES OF THE SEA URCHIN EMBRYO
海胆胚胎特定细胞类型的全球基因调控网络
基本信息
- 批准号:8149931
- 负责人:
- 金额:$ 66.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-09-30 至 2015-05-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAnimalsBioinformaticsBiological ModelsBiological ProcessCell LineageCell physiologyCellsCellular biologyClinicalCodeComplementary DNAComplexConserved SequenceDevelopmentDevelopmental GeneDiseaseEffector CellEmbryoEndodermEndoderm CellExcisionFluorochromeGene ExpressionGene Expression ProfileGenesGenomicsImmuneInstructionIntergenic SequenceKnock-in MouseKnowledgeLearningLifeLinkMeasurementMediatingMesodermMethodsMorphogenesisNatural ImmunityOralPattern FormationPhysiologicalPopulationPrimitive foregut structureProblem SolvingProceduresProcessProteinsProxenRecoveryRegulator GenesResearchSea UrchinsSequence AnalysisSignaling MoleculeSiteSolidSolutionsStagingStructureSystemTechnologyTimeTo specifyValidationWorkblastomere structurecell typeeggembryo cellgastrulationgenome sequencinginterestnetwork modelspublic health relevanceresearch studysuccesstranscription factor
项目摘要
DESCRIPTION (provided by applicant): All developmental, morphogenetic, and differentiation functions of animal cells are executed by large, specifically deployed batteries and cassettes of downstream protein coding genes. A major success of bioscience in recent years has been system level elucidation of the upstream gene regulatory networks (GRNs) that control pattern formation and determine development of the body plan. GRNs consist of genes encoding transcription factors and signaling molecules, plus the transcriptional linkages among these genes, and they determine the regulatory state of every cell at every point in developmental time. Therefore they include the control inputs into all the downstream genes that do the work of the cell. But an enormously important gap in understanding now separates the upstream GRNs that we are beginning to learn about from the downstream effectors of cell function: What is the actual control circuitry that determines the deployment of these downstream genes? How, exactly, are GRNs causally connected to cellular functions of differentiation and morphogenesis? In principle, given knowledge of the upstream GRN and various newly available technologies, this gap can be closed, and the problem solved at a system level, and this is the particular object of the present proposal. We will choose three cell types of the developing sea urchin embryo, each of general interest. Knowledge of the upstream GRNs of this embryo is more advanced than for any other system. The target cell types are the immune cells of the embryo, where the downstream effector genes encode a great variety of innate immunity proteins; gastrulating endoderm cells, where the downstream genes mediate gastrular invagination; and the totipotent set-aside cells of the embryonic coelomic pouches that in larval stage produce the adult body plan, where the downstream effector cells include those that maintain totipotency. Innate immunity, gastrular invagination, and totipotent cell lineages are all pan-bilaterian features. The approach, briefly, will be isolation of each cell type using specific regulatory gene expression and FACS; deep transcriptome sequencing; bioinformatic prediction; and validation of causal regulatory connections to specifically expressed genes by high throughput cis- regulatory analysis. This project will provide the first global upstream-downstream GRN for any developing system. It will inform as to basic principles by which downstream gene cassettes are organized. It will also serve as a technological demonstration project for similar approaches to mammalian systems.
PUBLIC HEALTH RELEVANCE: This work is about finding the causal lines of control that determine how fundamental life processes are executed according to the instructions encoded in the genomic regulatory system. The most powerful approach to general solutions to complex disease states requires solid understanding of their control circuitry. Our practice must get beyond struggling to ameliorate effects rather than altering causes. This research shows the way to discovery of structure and function in causal genomic control systems.
描述(由申请人提供):动物细胞的所有发育、形态发生和分化功能均由下游蛋白质编码基因的大型专门部署的电池和盒执行。近年来,生物科学的一个重大成功是对上游基因调控网络(GRNs)的系统水平阐明,该网络控制模式形成并决定身体计划的发展。GRNs由编码转录因子和信号分子的基因以及这些基因之间的转录联系组成,它们决定了每个细胞在发育过程中每个点的调控状态。因此,它们将控制输入包括到所有下游基因中,这些基因完成细胞的工作。但是,我们现在对上游GRNs的理解与对下游细胞功能效应子的理解存在着巨大的差距:决定这些下游基因部署的实际控制电路是什么?究竟GRNs与细胞分化和形态发生的功能有何因果关系?原则上,在已知上游GRN和各种新可用技术的情况下,可以弥合该差距,并且在系统级解决问题,这是本建议的特定目标。我们将选择三种发育中的海胆胚胎细胞类型,每种都是普遍感兴趣的。对这个胚胎的上游GRNs的了解比任何其他系统都要先进。靶细胞类型是胚胎的免疫细胞,其中下游效应基因编码多种先天免疫蛋白;原肠胚内胚层细胞,其中下游基因介导原肠胚内陷;以及胚胎体腔囊的全能性预留细胞,其在幼虫阶段产生成体体平面,其中下游效应细胞包括维持全能性的那些。先天免疫、原肠胚内陷和全能细胞谱系都是泛双侧性特征。简言之,该方法将是使用特异性调控基因表达和FACS分离每种细胞类型;深度转录组测序;生物信息学预测;以及通过高通量顺式调控分析验证与特异性表达基因的因果调控联系。该项目将为任何开发中的系统提供第一个全球上下游GRN。它将告知下游基因盒组织的基本原则。它还将作为对哺乳动物系统采取类似办法的技术示范项目。
公共卫生相关性:这项工作是关于找到因果控制线,决定如何根据基因组调控系统中编码的指令执行基本生命过程。最有效的方法来解决复杂的疾病状态需要坚实的理解他们的控制电路。我们的实践必须超越努力改善影响,而不是改变原因。这项研究显示了因果基因组控制系统的结构和功能的发现的方式。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ERIC H DAVIDSON其他文献
ERIC H DAVIDSON的其他文献
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{{ truncateString('ERIC H DAVIDSON', 18)}}的其他基金
Depth and Breadth of Explanatory Power in Developmental GRNs
发展 GRN 解释力的深度和广度
- 批准号:
8752112 - 财政年份:2014
- 资助金额:
$ 66.63万 - 项目类别:
GLOBAL GENE REGULATORY NETWORKS FOR SPECIFIC CELL TYPES OF THE SEA URCHIN EMBRYO
海胆胚胎特定细胞类型的全球基因调控网络
- 批准号:
8288724 - 财政年份:2010
- 资助金额:
$ 66.63万 - 项目类别:
GLOBAL GENE REGULATORY NETWORKS FOR SPECIFIC CELL TYPES OF THE SEA URCHIN EMBRYO
海胆胚胎特定细胞类型的全球基因调控网络
- 批准号:
8022781 - 财政年份:2010
- 资助金额:
$ 66.63万 - 项目类别:
Global Genomic Regulatory Code for the gastrula stage sea urchin embryo
原肠胚阶段海胆胚胎的全球基因组监管代码
- 批准号:
8092699 - 财政年份:2010
- 资助金额:
$ 66.63万 - 项目类别:
Specialized Research Support Core (SRC CORE)
专业研究支持核心(SRC CORE)
- 批准号:
8092702 - 财政年份:2010
- 资助金额:
$ 66.63万 - 项目类别:
GLOBAL GENE REGULATORY NETWORKS FOR SPECIFIC CELL TYPES OF THE SEA URCHIN EMBRYO
海胆胚胎特定细胞类型的全球基因调控网络
- 批准号:
8463580 - 财政年份:2010
- 资助金额:
$ 66.63万 - 项目类别:
Scientific and Administrative Coordination Core (SAC CORE)
科学和行政协调核心(SAC CORE)
- 批准号:
8092703 - 财政年份:2010
- 资助金额:
$ 66.63万 - 项目类别:
Egg to Embryo: Gene Regulatory Circuitry in Development
卵子到胚胎:发育中的基因调控回路
- 批准号:
8049418 - 财政年份:2010
- 资助金额:
$ 66.63万 - 项目类别:
Egg to Embryo: Gene Regulatory Circuitry in Development
卵子到胚胎:发育中的基因调控回路
- 批准号:
7881821 - 财政年份:2009
- 资助金额:
$ 66.63万 - 项目类别:
Global Genomic Regulatory Code for the gastrula stage sea urchin embryo
原肠胚阶段海胆胚胎的全球基因组监管代码
- 批准号:
8055256 - 财政年份:2009
- 资助金额:
$ 66.63万 - 项目类别:
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