Functional Genomics in a Simple Model Metazoan

简单模型后生动物的功能基因组学

• 批准号: 7309580
• 负责人: MARK q MARTINDALE
• 金额: $ 6.92万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-20 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7309580
• 关键词: Animals; Bilateral; Biological Models; Cellular biology; Cnidaria; Data; Department of Energy; Development; Disease; Electroporation; Embryo; Enhancers; Event; Evolution; Expressed Sequence Tags; Future; Gene Expression; Genes; Genetic; Genetic Variation; Genome; Germ; Germ Layers; Goals; Health; Human; Human Biology; Human Resources; Insertional Mutagenesis; Institutes; Investigation; Joints; Label; Life; Mediating; Microinjections; Modeling; Molecular; Nematoda; Nuclear; Nucleic Acids; Pathway interactions; Pattern; Phylogenetic Analysis; Positioning Attribute; Procedures; Radiation; Recording of previous events; Regulatory Pathway; Reporter; Research; Solid; Stem cells; Techniques; Technology; Testing; Transgenes; Transgenic Animals; Uncertainty; Variant; Vertebrates; Work; base; cell type; fly; functional genomics; gene discovery; gene function; genome sequencing; homologous recombination; insight; neurodevelopment; programs; research study; tool; vertebrate genome

DESCRIPTION (provided by applicant): This application will develop robust techniques to manipulate gene expression and investigate gene function in embryos of an important new metazoan model system, Nematostella vectensis. Surprising new results from total genome sequencing and EST analyses of N. vectensis indicate that vertebrates share greater similarities in genome content with cnidarians like N. vectensis than either do with flies or nematodes. This revelation casts doubt on the significance that derived genetic model systems may have on human biology and thus provides the opportunity to understand the ancestral relationships between genetic variation and morphological complexity. The crucial phylogenetic position of N. vectensis will allow an understanding of the differences in the molecular control of developmental patterning seen in vertebrates, but absent in derived ecdysozoan genetic models systems, providing important insight into the ancient molecular patterning mechanism deployed before the radiation of vertebrate lineages. Being able to experimentally dissect molecular pathways in these animals is crucial to understanding the origin of variation in genetic regulatory networks involved in normal human health and disease. This work takes advantage of the complete genome sequencing of N. vectensis by the Joint Genome Institute (Department of Energy) and will provide additional technical and methodological background for future experiments in the field. This application will substantially enhance our ability to launch a long term research program for gene discovery and functional investigations of genetic regulatory pathways common to all living animals. The aims of this application are: Specific Aim 1: to optimize electroporation delivery techniques for transgene applications. Specific Aim 2: to create stable transgenic animals using transposon mediated insertion technology. Specific Aim 3: generate transgenic animals expressing loci marked through homologous recombination of BAC clones. Expression constructs have already been generated and solid preliminary data along with personnel with proven history of accomplishment insure that rapid progress will be made. These data will provide the technical basis for gene discovery for important developmental events such as germ layer formation during gastrulation, origin of bilateral symmetry, neural development/organization, and somatic/germ stem cell biology by enhancer trap techniques and for the functional analysis of gene network evolution by insertional mutagenesis.

描述（由申请人提供）：此应用将开发出强大的技术来操纵基因表达并研究重要的新后生动物模型系统Nematostella vectensis的胚胎中的基因功能。 令人惊讶的是，基因组测序和对静脉乳杆菌的EST分析的新结果表明，脊椎动物在基因组含量中与静脉弧菌（如N. vectensis）具有更大的相似性。 这种启示对衍生的遗传模型系统可能对人类生物学具有的重要性产生了怀疑，因此提供了理解遗传变异与形态复杂性之间祖先关系的机会。 N. vectensis的至关重要的系统发育位置将使您了解脊椎动物中观察到的发育模式的分子控制的差异，但在衍生的Ecdysozoan遗传模型系统中不存在，从而为在部署椎骨线辐射之前部署的古代分子模式机制提供了重要的见解。 能够实验剖析这些动物的分子途径对于理解与正常人类健康和疾病有关的遗传调节网络变异的起源至关重要。 这项工作利用了联合基因组研究所（能源部）对N. vectensis进行完整的基因组测序，并将为该领域的未来实验提供其他技术和方法论背景。 该应用将大大提高我们启动长期研究计划的能力，以进行基因发现和对所有活体动物常见的遗传调节途径的功能研究。 该应用的目的是：特定目的1：优化用于转基因应用的电穿孔输送技术。 特定目的2：使用转座子介导的插入技术创建稳定的转基因动物。 特定目标3：产生通过BAC克隆同源重组标记的基因座的转基因动物。 表达结构已经生成和扎实的初步数据，以及具有可靠成就史的人员，可以确保快速进步。 这些数据将为重要发育事件的基因发现提供技术基础，例如胃层，双侧对称性的起源，神经发育/组织的起源，以及通过增强子陷阱技术以及通过插入性突变发生的基因网络进化的功能分析。