Songbird Neurogenomics Initiative

鸣鸟神经基因组学计划

• 批准号: 6845131
• 负责人: DAVID F CLAYTON
• 金额: $ 35.52万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6845131
• 关键词: Internet; functional /structural genomics; gene expression; genetic regulation; genome; high throughput technology; informatics; interdisciplinary collaboration; learning; microarray technology; molecular biology information system; neurogenetics; nucleic acid sequence; songbirds

DESCRIPTION (provided by applicant): The songbird model system has made novel and important contributions to a number of areas of neurobiological research, and stands as one of the most powerful models for studying the role of gone regulation in neural plasticity. The goal of this proposal is to apply powerful new methods of genomics to the further study and development of this model. A consortium of seven songbird investigators, at six different institutions in the U.S., will work with the Keck Center for Comparative and Functional Genomics at the University of Illinois, to establish: a) a collection of cDNA clones representing the mRNAs in the zebra finch brain; b) a database of expressed sequence tags (ESTs) derived by high-throughput sequencing of the collection; c) a web-based publicly accessible server for analysis of the EST database; d) generations of glass microarrays containing a "unigene" set of ESTs plus control DNAs; e) optimized protocols for hybridization of microarrays with RNA probes derived from zebra finches and other songbirds. All these resources will be made available to the larger scientific community at low cost. The consortium will specifically apply these tools to a range of objectives defined in their currently-funded research programs. Additionally, pilot experiments will be conducted to confirm and extend four aspects of differential gene expression in the zebra finch brain: 1) gene induction associated with song perceptual learning in adults; 2) gene regulation within specific song nuclei during the critical period for song learning in juveniles (a paradigm specifically relevant to functional study of the Parkinson's Disease-linked gene, alpha-synuclein); 3) differential expression of song nucleus-specific or enriched genes; 4) differential expression of genes associated with brain sexual differentiation. To encourage refinement and widespread use of these resources, a periodic workshop for all interested investigators will be organized, and an Advisory Board representing the larger songbird research community will be appointed and consulted regularly. A key aspect of this proposal is the application of the cost-effective and proven resources of the Keck Center, which have been successfully used to develop similar genomics toolsets for other non-mainstream model organisms, including honeybees and cattle. This project will have both immediate and long-term consequences for research into a number of issues relevant to human health and disease, including molecular mechanisms involved in learning, control of sexual differentiation, effects of steroids on brain function and development, and processes that promote or limit brain cellular plasticity and repair.

描述（由申请人提供）：鸣禽模型系统对神经生物学研究的许多领域做出了新颖和重要的贡献，并且是研究神经元调节在神经可塑性中的作用的最有力的模型之一。该提案的目标是将强大的基因组学新方法应用于该模型的进一步研究和开发。一个由美国六个不同机构的七名鸣鸟调查员组成的联盟，将与伊利诺伊大学凯克比较和功能基因组学中心合作，建立：a）代表斑胸草雀脑中mRNA的cDNA克隆集合; B）通过高通量测序获得的表达序列标签（EST）数据库; c）用于EST数据库分析的基于网络的公共访问服务器; d）含有“单基因”EST组加对照DNA的玻璃微阵列的世代; e）用于微阵列与来自斑胸草雀和其他鸣禽的RNA探针杂交的优化方案。所有这些资源都将以低成本提供给广大科学界。该联盟将专门将这些工具应用于其目前资助的研究计划中定义的一系列目标。此外，本研究还将通过初步实验来证实和扩展斑胸草雀大脑中基因表达差异的四个方面：1）与成年斑胸草雀鸣唱感知学习相关的基因诱导; 2）在幼年斑胸草雀鸣唱学习关键期特定鸣唱核团中的基因调控（与帕金森病相关基因α-突触核蛋白的功能研究特别相关的范例）; 3）鸣唱核特异性或富集基因的差异表达; 4）脑性别分化相关基因的差异表达。为了鼓励这些资源的完善和广泛使用，将为所有感兴趣的研究人员组织定期讲习班，并将任命一个代表更大的鸣禽研究界的咨询委员会，并定期征求意见。这一提议的一个关键方面是应用凯克中心具有成本效益和经过验证的资源，这些资源已成功用于为其他非主流模式生物（包括蜜蜂和牛）开发类似的基因组学工具集。该项目将对研究与人类健康和疾病有关的一些问题产生直接和长期影响，包括学习的分子机制、性别分化的控制、类固醇对脑功能和发育的影响以及促进或限制脑细胞可塑性和修复的过程。