The University of Colorado Denver, Anschutz Medical Campus has a strong and growing structural biology community, illustrated by our recent successes in macromolecular crystallography and increasing number of users of the x-ray crystallography core facilities. To build on this excellence and enhance our ability to support the commitment of the NIH to structural biology, we propose to purchase X-ray data collection system consisting of: 1) a rotating anode X-ray generator;2) an area detector;and 3) upgrade of an existing imaging plate system, X-ray optics, cryo-cooling systems, and visualization systems to replace the current aging X-ray system. This equipment will allow for more rapid screening and data collection, will facilitate data collection from small crystals and those with large unit cells, and will be a cost effective approach to maintaining this vital resource that is shared among more than a dozen productive researchers. The University has made a commitment to this proposal by providing dedicated and prepared space, matching funds, and salary support for a facility manager. This equipment will have an immediate and lasting impact on NIH-funded research in areas as diverse as virology, cancer, RNA splicing, gene regulation, addiction, infectious diseases, and protein synthesis. Specific benefits include: Increased productivity: The area detector, X-ray generator and improved optics will enable us to screen more crystals much more quickly, and will allow us to screen smaller crystals and those with quite large unit cells before sending them to the synchrotron. Data collection in house: Datasets of improved quality will be collected much more rapidly and from smaller crystals than were previously possible, which will increase the throughput of the facility. Cost savings. Infrastructure and maintenance costs will be lower with the more energy efficient system.
The x-ray data collection instrumentation requested in this application will be used for the determination of three dimensional crystal structures of proteins, DNA, RNA, and their complexes to provide insight into basic biological processes and diseases such as hepatitis, bacterial and parasitic infections, and breast cancer. Any serious attempt to combat these, and other diseases, must include an effort to solve macromolecular structures at atomic resolution, which provides information critical for rational drug design. The proposed equipment will directly impact the rate at which we can solve important structures, the number of projects we can tackle, and our ability to obtain particularly challenging structures that will generate insights into and eventually treatments of human disease.