Objective: The Structural Biology Shared Resource (SBSR) provides UCCC researchers access to instrumentation and expertise in X-ray Crystallography and Nuclear Magnetic Resonance Spectroscopy, promoting the application of macromolecular structural studies to cancer research. Projects studied in the Core include hormone receptor and transcription regulator structures, telomere structures, tumor suppressor structures, phospholipid targeting domain structures, tumor cell surface marker structures, and chromatin assembly and disassembly structures, among others, and have resulted in >50 research publications, including many publications in high profile journals such as Cell, Nature, Science, Molecular Cell, and Nature Structural and Molecular Biology. Services &Technologies: The facilities available within the resource have expanded significantly over the last 5 years. The X-ray Core facility has 2 Raxis IV++ area detectors with a Rigaku/MSC generator and has added Rigaku/MSC robotic systems for production of crystallization screens, drop setting and plate imaging. The NMR Core facility has added a 900 MHz Varian NMR spectrometer to the existing 500 and 600 MHz spectrometers at the Anschutz Medical Campus and has added a Varian 800 MHz spectrometer at the University of Colorado Boulder campus. Consultation &Training: SBSR personnel provide sample preparation, data collection and instrument training and help investigators process data, determine structures, and prepare data for publication and presentation. Utilization: In the last year, the SBSR supported the operation of more than 30 research programs including 18 UCCC members (with ~$3.8 million of annual direct costs in grant support) from 4 different UCCC Programs and 3 UCCC consortium institutions (UCD AMC, National Jewish Health, UC Boulder). UCCC members accounted for 88% of the total usage of the facilities. Management &Finances: SBSR is UCCC managed. Approximately one-quarter of the grants serviced by the SBSR are NCI-funded;however, many of the grants funded by other NIH agencies are specifically cancer-related. Other funding has come from the American Cancer Society, Cancer League of Colorado and the National Science Foundation. In the previous year, 43% of the operating budget came from chargebacks to UCCC members who represent >90% of users. The SBSR requests $180,693 CCSG support for 40% of its operating budget. Developing facilities for structural biology research will continue, and two primary future objectives are 1) develop new projects from non-structure labs, and 2) promote closer integration with clinical research as part of target validation.
Researchers in the Structural Biology Shared Resource determine the 3-dimensional structures of the proteins, other cellular macromolecules and their complexes that affect the development and progression of cancer, and of small molecules, potential drugs and their interactions with their therapeutic targets. Structures of molecules implicated in cancer provide clues to potential therapies.
|Saichaemchan, S; Ariyawutyakorn, W; Varella-Garcia, M (2016) Fibroblast Growth Factor Receptors: From the Oncogenic Pathway to Targeted Therapy. Curr Mol Med 16:40-62|
|Gillen, Austin E; Yamamoto, Tomomi M; Kline, Enos et al. (2016) Improvements to the HITS-CLIP protocol eliminate widespread mispriming artifacts. BMC Genomics 17:338|
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|Helfrich, Barbara A; Kim, Jihye; Gao, Dexiang et al. (2016) Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo. Mol Cancer Ther 15:2314-2322|
|Munson, Daniel J; Egelston, Colt A; Chiotti, Kami E et al. (2016) Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR. Proc Natl Acad Sci U S A 113:8272-7|
|Scott, Aaron J; Lieu, Christopher H; Messersmith, Wells A (2016) Therapeutic Approaches to RAS Mutation. Cancer J 22:165-74|
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