STRUCTURAL BIOLOGY SHARED RESOURCE (Core-405) ABSTRACT Overview: The Structural Biology Shared Resource (SBSR) aims to facilitate and promote the application of macromolecular structural biology methods in cancer research for UCCC members. SBSR meets these goals by providing UCCC members instrumentation and expertise in X-ray Crystallography (X-ray) and Nuclear Magnetic Resonance Spectroscopy (NMR). Examples of projects studied in the SBSR fall into three main topic areas: Dynamics of cancer target activity, gene regulation, chromatin and epigenetics, and molecular targeting for the development of novel anti-tumor agents. Equipment: The SBSR capabilities have expanded significantly over the last 5 years through institutional support and the NIH Shared Instrument Grant Program. As a result, the X-ray facility has acquired a new in-house data-collection system that consists of a Rigaku MicroMax-007 X- ray generator, PILATUS3 R 200K Hybrid Pixel Array Detector with VariMax Optics and Oxford cryo-cooling systems. It also has a Rigaku/MSC robotics system for production of crystallization screens, drop setting and plate imaging. The NMR facility is equipped with Agilent/Varian 500, 600 and 900 MHz spectrometers at the Anschutz Medical Campus and an Agilent/Varian 800 MHz spectrometer at the UCB campus. Services: The SBSR provides expertise and access to highly specialized instrumentation for X-ray crystallography and NMR based structural studies of biomolecules relevant in cancer biology. Consultation and Education: SBSR personnel provide advice on sample preparation, data collection, structure determination, and data presentation for publication. Hands-on instrument training is important function of SBSR staff. Management: The SBSR is an institutional core managed by the institution as part of the Structural Biology and Biophysics Core Facilities. CCSG funding represents 34% of the annual operating budget. The remaining support comes from institutional support (50%) and user fees (16%). In regard to UCCC, SBSR is overseen by the Associate Director for Basic Research. Use of Services: Since July 2011, 54 investigators have used the services. Thirty-five percent of users were UCCC members, representing five of the six UCCC Research Programs and resulting in 55 peer- reviewed publications. Future Directions: The SBSR has several primary future directions that will enhance the SR and UCCC member cancer research: 1) Outreach to UCCC members from non-structure labs to create awareness of the opportunities SBSR technology offers and provide training in such technology; 2) incorporate into SBSR the new Cryo-Electron Microscopy resources that are currently being developed; 3) Collaborate with PMTSR to develop a comprehensive protein expression and purification service; 4) Initiate lifecycle replacement of several NMR resources.
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