ABSTRACT Overview: The Structural Biology Shared Resource (SBSR) promotes and enables the application of macromolecular structural biology to cancer research by UCCC members. To achieve this, the SBSR provides state-of-the-art instrumentation and expertise in X-ray crystallography (X-ray), Cryo-electron microscopy (Cryo- EM) and Nuclear Magnetic Resonance Spectroscopy (NMR). Ongoing cancer-related projects in the SBSR include studies of the molecular mechanisms of gene expression, chromatin regulation and epigenetics, the dynamics of cancer target activity, and analysis of intermolecular interaction to aid the development of novel anti- tumor agents. Services and Expertise: The SBSR provides access to highly specialized instrumentation for structural analysis of biomolecules relevant in cancer biology and can offer technical and scientific assistance and expertise in all phases of a project, from experimental design to execution and result interpretation. Equipment: The SBSR is committed to providing access to cutting edge instrumentation. Over the last 5 years instrumentation has been upgraded and expanded through institutional support and the NIH Shared Instrument Grant Program. A new Bruker 600 MHz NMR spectrometer was acquired to complement existing equipment. Substantial support from the School of Medicine (SOM) made possible establishment of a state-of-the-art Cryo- EM facility, fully equipped for high-resolution cryo-EM structural analysis, and to upgrade the X-ray crystallization facilities. Management: The SBSR is part of the SOM's Structural Biology and Biophysics Core Facilities. Institutional support (45%) and user fees (39%) account for a majority of the annual operating budget with CCSG funding representing ~16% of the total. Within the UCCC, SBSR is overseen by the Associate Director for Basic Research. Use of Services: In the current funding cycle, of the 60 investigators who have used the SBSR, 18 (30%) were UCCC members from the MCO and THI Programs who accounted for 75% of the total use. SBSR- linked projects resulted in 61 peer-reviewed publications (41% with an IF>10) from 26 federal grants. Innovation and Development: As evidenced by the recent addition of Cryo-EM capabilities, the SBSR strives to maintain access to comprehensive, cutting-edge resources and outstanding technical and scientific expertise. Consultation and Education: SBSR personnel provide advice on all aspects of structural biology research, from sample preparation to interpretation and presentation of final results. A critical component of the SBSR's mission is to increase awareness and technical expertise in structural biology by providing training in all aspects of relevant techniques, from hands-on instrumentation training to data analysis and structure interpretation. Future Directions: Moving forward, the SBSR will increase its contribution to research by UCCC members through: 1) continued outreach to UCCC members to increase...