This proposal requests funds for the purchase of an area-detector facility for macromolecular crystallography. Requested equipment includes an image-plate area detector and associated computer for data collection, an X-ray generator, a heat exchanger, focusing mirrors, and cryogenic equipment for low temperature (100 K) data collection. This proposal is part of a major effort by the University of Utah to move from a single-investigator laboratory in the area of macromolecular crystallography to a multi-user facility. An important first step in this effort was the hiring of Dr. Ramakrishnan (P.I.) as a senior faculty member. The University also recently created a Research Assistant Professorship, currently held by Dr. Bancroft, whose duties include maintaining and upgrading X-ray equipment and associated computing. The expanded facility will be used to solve structures of macromolecules related to a wide variety of research at the University of Utah, including: HIV-1 structure and assembly, ribosome structure and function, chromatin structure, protein-RNA recognition, transcriptional regulation, ubiquitin biochemistry, protein turnover, isoprene biochemistry, and hypertension. Macromolecular crystallography at the University of Utah is currently being performed by Dr. Hill (co-P.I.). The Hill laboratory maintains and operates an R-axis II image-plate area-detector. A large number of projects, originating both within the Hill laboratory and in collaboration with others, have saturated the existing equipment. Indeed, many projects already languish for lack of available detector time. With the arrival of Dr. Ramakrishnan in September 1995, this already large demand will increase dramatically. Furthermore, the thriving biomedical research community at the University of Utah is increasingly focused on biological problems with essential structural components and this new emphasis will place increased demand upon the X-ray data collection facility in the near future. Finally, a number of new structural projects are expected to emerge with the recent opening of the Huntsman Cancer Center (est. 40 new faculty positions) and a new Genome Sequencing Center (focused on extreme thermophilic bacteria). Thus the purchase of a second data collection facility is essential and, indeed, the anticipated growth is expected to more than saturate even the expanded facility. The University of Utah will provide matching funds for 50% of the instrumentation requested in this proposal. A second significant University contribution to the expansion of macromolecular crystallography at Utah is the remodeling of space to provide the infrastructure necessary for an efficient, multiuser crystallographic facility. Following proposed remodeling, the major structural groups will occupy greater than 10,000 sq. ft. of contiguous space with extensive shared facilities including X-ray data collection and computer graphics suites, biophysical instrumentation laboratories, constant-temperature crystallization rooms, and preparative laboratories and cold rooms. In summary, the University has made a major commitment to create an expanded macromolecular crystallography facility that will both complement and serve a vital biomedical research community. The purchase of the new area detector facility described in this proposal is an essential step in realizing that goal.
