Washington University Center for Translational Neuroscience

提出了一个分子分析核心，为基础和临床研究人员提供咨询， 在基因组学和蛋白质组学技术，实验设计和数据解释方面的专业知识， 神经系统疾病的转化研究。方便获取Affyesterday基因芯片 用于进行基因表达分析和基于阵列的“全基因组”SNP的微阵列平台 基因分型，Sequenom技术平台，用于对大量 将提供样本和用于突变谱研究的候选基因毛细管重测序。 神经科学研究人员将优先获得当前和创新的蛋白质组学技术。 这些将包括分离复杂蛋白质混合物的仪器和方法， 样品处理和蛋白质鉴定和表征（例如，共价修饰），使用“状态- 与自动多维毛细管液相色谱联用的现有技术的串联质谱法 色谱仪。提出的神经蛋白质组学主题将是发现和验证蛋白质生物标志物， 测量人类疾病相关蛋白的体内代谢半衰期，定义功能蛋白 受体和离子通道的修饰，并表征新的蛋白质复合物。调查人员将 促进了在核心C内以及通过协调， 行政核心A的跨学科活动。统计评价、数据管理和 将与拟议的信息学核心G进行整合。这些新技术的应用 对神经系统疾病的研究有望彻底改变我们对这些疾病的理解， 帮助将基本神经生物学发现转化为诊断和治疗进展。

A Molecular Analysis Core is proposed for providing basic and clinical researchers with consultation and expertise in genomics and proteomics technology, experimental design, and data interpretation for translational studies in diseases of the nervous system. Facilitated access to the Affymetrix GeneChip microarray platform for performing gene expression analysis and array-based 'whole genome' SNP genotyping, the Sequenom technology platform for performing targeted genotyping on large numbers of samples, and candidate gene capillary resequencing for mutational profiling studies will be provided. Neuroscience investigators will have preferred access to current and innovative proteomics technology. These will include instrumentation and methods for the separation of complex protein mixtures, robotics for sample processing, and protein identification and characterization (e.g. covalent modifications) using 'state-of- the-art' tandem mass spectrometry coupled to automated multi-dimensional capillary liquid chromatographs. Proposed neuroproteomic themes will be discovery and validation of protein biomarkers, measuring in vivo metabolic half- lives of disease-associated proteins in humans, defining functional protein modifications on receptors and ion channels, and characterizing novel protein complexes. Investigators will have facilitated access to genomics and proteomics data both within Core C and through the coordinated, interdisciplinary activities of the Administrative Core A. Statistical evaluation, data management and integration will be provided with the proposed Informatics Core G. The application of these new technologies to diseases of the nervous system promises to revolutionize our understanding of these disorders and will help turn basic neurobiological discovery into diagnostic and therapeutic advances.