Songbird Neurogenomics Initiative

描述(申请人提供)：鸣禽模型系统在神经生物学研究的多个领域做出了新颖而重要的贡献，是研究GONE调控在神经可塑性中作用的最强大的模型之一。这项提议的目标是将强大的基因组学新方法应用于这一模式的进一步研究和发展。一个由七名鸣鸟研究人员组成的财团，来自美国六个不同的机构，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)用于分析EST数据库的网络公众可访问服务器；d)包含一组“Unigene”EST和对照DNA的多代玻璃微阵列；e)用于微阵列与来自斑雀和其他鸣禽的RNA探针的杂交优化协议。所有这些资源都将以较低的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他们目前资助的研究计划中定义的一系列目标。此外，还将进行初步实验，以确认和扩展斑雀大脑中差异基因表达的四个方面：1)与成人歌曲知觉学习相关的基因诱导；2)青少年歌曲学习关键期特定歌曲核内的基因调控(与帕金森氏病相关基因α-突触核蛋白的功能研究特别相关的范式)；3)歌曲核特定基因或丰富基因的差异表达；4)与脑性分化相关的基因的差异表达。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定期组织一次研讨会，并将任命一个代表更大的鸣禽研究社区的咨询委员会，并定期征询意见。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，这些资源已成功地用于为包括蜜蜂和牛在内的其他非主流模式生物开发类似的基因组学工具包。该项目将对一些与人类健康和疾病相关的问题的研究产生直接和长期的影响，包括与学习有关的分子机制，性别分化的控制，类固醇对大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.