BioCARS is a nationally-available research resource for synchrotron-based structural biology at Sector 14 of the Advanced Photon Source, Argonne National Laboratory, that exploits the distinctive features of BioCARS and complements other structural biology beamlines at the APS and nationally. Our chief scientific emphasis lies on time-resolved crystallography on time scales from 100 ps to s, in which a substantial collaborative user community is developing. Our two experimental stations are embedded in a BSL-3 facility to allow safe study of biohazards. Both the time-resolved and biohazards capabilities are unique in the USA. The recently-upgraded insertion device beamline 14-ID is served by two dissimilar, collinear undulator sources that deliver tightly-focused, intense, tunable, monochromatic or pink X-ray beams to the 14-ID-B station, suitable for both time-resolved and standard monochromatic experiments. The bending magnet beamline 14-BM is particularly suited to study crystals with large unit cells, or at ultra-high resolution. A laser laboratory houses ps and ns pulsed lasers and other optical instrumentation essential to the time-resolved experiments. Core research and development concentrates on time-resolved crystallography. We will implement new methods for exploring irreversible reactions based on pixel array detectors, on a novel use of an existing image plate detector and on crystal rotation geometry. We will develop a new capability to study small to microcrystals with both monochromatic and Laue techniques, and examine the ultrafast time course of radiation damage at room and cryo temperatures. The small to microcrystal capability supports broadly other core R&D, collaborative and service activities. Collaborative research focuses on time-resolved crystallography and thus drives our core R&D activities. Service emphasizes study of biohazards, both as single crystals (often with large unit cells) and where feasible, as fibers or less-ordered samples;and of small to microcrystals. We will continue our high levels of user training, and of dissemination to both expert and non-expert, wider audiences, by electronic, print and face-to-face approaches. In all cases, we assist users in solving transient and static, atomic-level structures of direct relevance to significant biomedical problems. Some of these structures will be of biohazards classified at the BSL-3 level;examples include human pathogenic viruses such as West Nile virus and prions. Others such as anthrax related toxins or enzymes are key to the metabolism of pathogenic microorganisms. They are both of substantial public health interest in their own right and may yield information directed at responses to bioterrorism. Yet others, particularly the transient structures, provide a novel view of mechanisms of action, and thus underlie the development of more effective therapeutic agents.
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