Synchrotron radiation (SR) from electron storage rings provides an extremely intense and tunable source of x-rays which has broad applicability to studies in structural molecular biology (SMB). A Biotechnology Resource funded by the NIH BRTP program is established at the Stanford Synchrotron Radiation Laboratory (SSRL) to study the structure and dynamics of biological materials using protein crystallography, x-ray absorption spectroscopy and x-ray small angle scattering. This proposal is for the continued funding, operation and further development of this Resource and its infrastructure for SR-based SMB research. In each of the three methodology areas, new initiatives are planned which are centered around novel x-ray instrumentation and new detectors.
Major aims i nclude development of advanced methods and instrumentation for: multiple-wavelength protein data collection and phasing; time-resolved structural changes using """"""""white"""""""" radiation crystallography (Laue) and small angle scattering; time-resolved protein crystallographic studies using fast monochromatic methods; cryocrystallography; CCD-based detection systems for x-ray crystallographic and scattering data from biomolecules; advanced solid- state multielement array detectors for dilute XAS measurements; new instrumentation to provide for small angle X-ray scattering in the very low angle region; instrumentation for XAS investigations in the 0.5-1.0 keV spectral region; and software development in all areas for real-time, on-line data analysis. These developments will continue to be supported by strong technological and core-collaborative research programs that include both Stanford and outside scientists. Relevance is to a number of important biological problems including the structure of enzymes, metalloproteins, membrane-bound proteins and immunoglobulins; the active site structure of metalloproteins involved in oxygen metabolism, nitrogen fixation, and photosynthesis; and how these structures change in different states or evolve in time as reactions occur. Such information is more broadly important to areas relevant to health that include design of new drugs, gene regulation and malignant transformation, and viral infection. An important ongoing goal is to provide support for these new facilities and to make them widely available to the national and international scientific user community. The program will continue to provide the opportunity for training of researchers in the use of this state-of-the-art instrumentation through workshops and tutorials. SSRL is now fully dedicated to synchrotron research and provides effective beam time for many months per year, enabling the resource to effectively serve a large biomedical user community. The Resource will continue to provide leadership in applications of SR to solve problems at the forefront of biophysics and structural molecular biology research.
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