INFORMATICS CENTER FOR MOUSE NEUROGENETICS

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DESCRIPTION (Applicant's Abstract): The purpose of this Neuroinformatics project is to develop and exploit a suite of image databases, motorized Internet microscopes, and software to study the genetic basis of structural variation of the mouse CNS. Resources are open to the research community through an integrated web interface at <nervenet.org>. The focus of this project is to provide a collaborative research environment for mapping quantitative trait loci (QTLs). These genes are responsible for the extraordinary variation in CNS structure among mice and humans. QTL analysis is a burgeoning field that tackles complex biological traits modulated by many genes. We will develop four significant new resources and technologies: (1) The Mouse Brain Library (MBL) consists of a huge, well-organized library of brain sections suitable for morphometric investigation. Thousands of images can be rapidly searched, sorted, and downloaded at a resolution of 5 microns per pixel using an intuitive and powerful web interface. (2) The Internet Microscope System (iScope) captures and displays extremely detailed movies -z-axis image stacks-suitable for sophisticated stereological study of all brains in the MBL. The iScope includes robotic slide handlers controlled over the web 24 hours a day, 7 days a week (3) The NeuroCartographer Project will develop a suite of software tools and 3D models of hundreds of neuroanatomical structures that will enable researchers to reconstruct and digitally dissect; material in the MBL. (4) The Neurogenetics Tool Box (NTB) comprises a set of gene mapping programs that will enable neuroscientists to rapidly identify and evaluate QTLs responsible for the astonishing variation in CNS architecture. The NTB will include genotypes from an unusually large advanced intercross designed to map loci with sufficient precision to enable a candidate gene approach to cloning QTLs. Achieving the aims of these four projects will catalyze a new era in the structural analysis of the adult mammalian nervous system and will lead to a large number of novel lines of research on the development, aging, and pathology of the human brain.