Songbird Neurogenomics Initiative

鸣禽模型系统对神经生物学的许多研究领域做出了新颖而重要的贡献，是研究神经可塑性中神经调节作用的最有力模型之一。本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。来自美国6个不同机构的7名鸣禽研究人员将与伊利诺斯大学的Keck比较与功能基因组学中心合作，建立：A)代表斑胸草雀大脑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)一个基于网络的可公开访问的服务器，用于分析无害环境技术数据库；d)几代玻璃微阵列，其中包含一组“单一”的est和对照dna；e)优化了微阵列与来自斑胸草雀和其他鸣禽的RNA探针的杂交方案。所有这些资源都将以低成本提供给更大的科学界。该联盟将专门将这些工具应用于其当前资助的研究项目中定义的一系列目标。此外，我们还将进行先导实验，以证实和扩展斑胸草雀大脑中基因表达差异的四个方面：1)成年雀鸣叫感知学习相关的基因诱导；2)在青少年鸣叫学习的关键时期，特定鸣叫核内的基因调控（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)歌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。为了鼓励改进和广泛使用这些资源，将为所有感兴趣的研究人员组织一次定期研讨会，并将任命一个代表较大鸣禽研究界的咨询委员会，并定期进行咨询。该提案的一个关键方面是应用Keck中心的成本效益和已证实的资源，这些资源已成功地用于开发其他非主流模式生物（包括蜜蜂和牛）的类似基因组工具集。该项目将对与人类健康和疾病有关的若干问题的研究产生直接和长期影响，包括参与学习的分子机制、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。

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.