B1. OBJECTIVE The Proteomics Core aims to provide all investigators at the Children's/Harvard IDDRC with access to the state-of-the-art mass spectrometry-based proteomics required to advance studies in the cell and molecular biology of neurodevelopmental disabilities. This core provides instruction, consultation and service for the analysis of proteins by mass spectrometry, including protein identification, characterization of post-translational modifications, and quantification of proteins in samples with a wide range of complexities. Overview. Mass spectrometry-based proteomics is currently the most sensitive, quantitative and comprehensive technology available for the characterization of proteins. A major goal of Core B is to use proteomics to assist IDDRC investigators in the identification of protein complexes relevant to neuronal function, to measure the quantitative changes in protein composition that occur in the nervous system during development and under conditions that lead to developmental disabilities, and to identify functional posttranslational modifications of neuronal proteins. Proteomics is a rapidly progressing field and the Core is committed to introducing and implementing new methodology and applications as they become available. Dr. Steen, an Assistant Professor in the Neurobiology Program at Children's Hospital, and an expert in protein biochemistry and mass spectrometry, was recruited to setup and now act as director of the IDDRC Proteomics Core located within the Kirby Neurobiology Center at Children's. The Steen Laboratory is actively involved in proteomics research and has a computational/bioinformatics subgroup, which develops proteomics related statistical and data analysis tools and provides access to this statistical and computational expertise via the Core to all members of the IDDRC. The Core provides advice and the technology for protein quantification and comparative proteomics to IDDRC members. This Core has been designed to provide qualitative and quantitative mass spectrometry-based proteomics technologies. Since the inception of the Proteomics Core in 2005, these powerful proteomic technologies have been successfully used in many IDDRC laboratories for the proteomic analysis of cells and tissues to study intellectual and developmental diseases. The application of proteomic techniques to the study of the developing brain is poised to accomplish i) characterization of the full constellation of proteins in defined cells and tissues, ii) an assessment of changes in protein content or modifications as a function of disease or change in cell state, and iii) characterization of protein function. These investigations involve both large scale and directed proteomic experiments. Large scale studies are often quantitative, involving isotope tagging methods to find differentially expressed or modified proteins;whereas directed studies examine the structure of a single protein including its co-translational and post-translational modifications with respect to the protein's function. The proteomics Core provides services which encompass both these areas. Genome sequencing has provided the opportunity to address questions regarding brain development, disease and dysfunction using approaches previously impossible. To understand the molecular mechanisms of intellectual development and pathophysiology, IDDRC investigators can now directly interrogate the """"""""proteome"""""""" of cells or tissues. This Core will provide a critical interactive center for IDDRC investigators by providing protein identification services, post-translational modification analyses and protein quantification.
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