We propose to continue the operation of the Biophysics Collaborative Access Team (BioCAT) undulator beamline 18ID at the Advanced Photon Source, Argonne National Laboratory. BioCAT's mission is to provide a national research resource for the study of partially ordered biological molecules, complexes of biomolecules, and cellular structures under conditions similar to those present in living cells. The goal of this research is to understand the detailed mechanisms of action of such systems at the molecular level. Health issues that are directly addressed are function and regulation of skeletal and cardiac muscle;collagenous structures and interactions with collagen binding proteins that have roles in heart disease and cancer;structure of amyloids, neurofibrillary tangles, metal metabolism and relationship to neurodegenerative disease. Basic biomedical questions that are addressed include the structure and dynamics of macromolecular complexes in solution, kinetics of protein and RNA folding, and roles of metal metabolism in development. The techniques employed are small- and wide-angle x-ray diffraction, x-ray solution scattering and x-ray absorption/emission spectroscopy with micro-beams. The BioCAT facilities provide a resource that is unique on the continent;only SPring-8 in Japan and the ESRF in France provide similar capabilities. Core developments are planned in: 1) Time and spatially resolved Fiber Diffraction for study of muscle, connective tissues, viruses, and structures associated with neurodegerative diseases. 2) Expanded Q-range, high-time resolution and high-throughput small-Angle X-ray Scattering for the study of the low resolution structure of macromolecules in complexes, determination of protein folds in small proteins and domains and time resolved studies of protein and RNA folding. 3) High efficiency microprobe for studies of metal mapping, speciation and local structure as related to cancer, development, and neurodegenerative diseases. Together, these projects will provide both entirely new capabilities and significantly enhanced existing capabilities to our collaborative and service users. Dissemination and training activities will make these capabilities known and available to the wider biomedical community.
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