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.
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