Synchrotron beam time has always been a needed and limited resource for macromolecular crystallographers, even with the advancements seen in higher brilliance facilities. Improvements in protein expression and crystallization have expanded the number and range of biologically interesting targets, the number of researchers capable of conducting this type of research, and the high value of the information obtained from such studies. Recently, with NIH and DOE support, the macromolecular crystallography beamlines in the United States are becoming more automated with the installation of robotic crystal sample changers that have impressive robustness and utility. With the improvement in beam line efficiency, in-house pre-screening of protein crystals becomes limiting leading to extensive screening of samples at the synchrotron beam lines (screening time estimated at 70% by several different laboratories), particularly for membrane proteins, protein-protein complexes, and structural genomics efforts. Because of limited synchrotron beam time and the improvements in the other aspects of protein crystallographic research, one (1) can no longer screen all of the crystalline samples available and therefore there is a critical need for robotics equipment on in-house x-ray sources, particularly for institutions with very large crystallographic communities. The opportunity to substantially improve the quantity and quality of the crystal screening process in the home laboratory will result in much more efficient usage of synchrotron beamtime as well as enabling new scientific knowledge gained from the subsequent structural studies. We are thus requesting funds to purchase an automated crystal sample changing and characterization system capable of automatically mounting, aligning, imaging (visual & diffraction) and dismounting batches of 288 cryogenically-cooled crystals on an in-house high brilliance (FR-D) x-ray source. The robotics system is identical to that at SSRL, using the 96 pin cassette system that can also handle pucks from the MSC/ALS robotics system. 15 NIH funded research laboratories at TSRI and the Burnham Institute (~180 researchers) plan to utilize the automated screening facility.
