X-ray structure analysis is a critical tool for a large group of major researchers at the University of Illinois at Chicago (UIC), a group whose annual research funding currently totals 4 million(Sec III). Seven laboratories are engaged in ten different macromolecular structure projects that require area detector technology. There is now a campus wide effort for establishing a comprehensive, centralized x-ray diffraction facility at UIC to serve the many needs of these basic science research projects. As part of that larger plan, this proposal if for acquisition of a state-of-the-art area detector and related equipment for macromolecular crystallography. Proposed Instrumentation. The equipment to be procured from this proposal consists of five main components: 1) a rotating anode x-ray generator, the strongest in-house source of x-ray photons available; 2) an area detector, for the most efficient measurement of the thousands of diffraction data; 3) a low temperature device, for lifetime extension of the radiation sensitive samples; 4) a host computer, for detector operation, and primary data collection and processing; and 5) a graphics workstation and software, for calculation of structures from the data, and display and analysis of the results. Price quotes and product information for the x-ray equipment have been received from four different suppliers. Although the detailed budget (Appendix V, p.20) is written for one specific supplier, the other quotes are at an equivalent total amount. The actual make of the equipment and type of area detector to be procured (fluorescent screen vs. imaging plate vs. multiwire) will be finalized after detailed performance comparisons if an award is made. Research and Training to be Conducted. The research activities to be conducted with the proposed x-ray equipment will be three-dimensional structural determination of molecules. Structures of biological macromolecules will consti tute the majority of the work. These include the protein crystallography projects described in the research activities section (pp. 4-11) The non-biological macromolecule projects (metallocluster compounds) require are detector technology in that their cell dimensions, solvent content, and radiation sensitivity rival those of standard protein crystallography work. The training will be primarily for doctorate level graduate students from the participating departments. The structural aspects of their research will be supervised by a core of three principal investigators with expertise in x-ray structure determination, who will closely interact with the interested laboratories. The training will concentrate on the application of x-ray structure analysis to their basic science research projects. An important feature of the planned x-ray facility will be in its relationship to the Molecular Biology training program initiated this year at UIC. The program includes three of the six departments participation in this proposal (Microbiology & Immunology, Biochemistry, and Physiology & Biophysics). The structural biology component of the training program will be substantially enhanced by the presence of the x-ray facility. In turn, this arrangement will increase the pool of potential graduate students for structural biology, and thus promote utilization of the x- ray facility to its maximum potential. Activity Resulting from Funding. An x-ray at UIC will have a significant impact on research performance on our campus by providing the necessary crystallographic tools for the ongoing structural projects. This will improve the success rate of our many laboratories in securing external agency funds. Because the facility will bring a focus to structural analysis for our multidisciplinary group of basic science researchers, it will also foster interaction and further collaboration among the participants.
