Ttie Structural Biology Shared Resource brings togethier Crystallograpfiy, NMR, and Protein Production & Analysis into a single facility, with Dr. Liddington as its Scientific Director and two Facility Directors/Managers who oversee day-to-day operations. This merger has brought the two complementary techniques for determining 3-dimensional structures of biological macromolecules at atomic resolution together with facilities for the large-scale production and biophysical characterization of proteins, technologies that are not available in individual Cancer Center laboratories owing to their expense and complexity. These developments have created a seamless Resource that is transforming the ability of scientists with little prior experience in structural biology to incorporate structural and structure-function studies as well as chemical biology into their research programs. The expanded facility has served the needs of more than 40 Cancer Center investigators over the last few years. The Institute has provided major equipment upgrades in crystallography, including a high brilliance generator fully equipped for data collection on two ports, together with a crystallization robot and storage/imaging "hotels";a new cryoprobe for the 600 MHz NMR instrument and a new "walk-up" 400 MHz instrument optimized for rapidly tuning to different nuclei and high-throughput sample-changing;and a complete laboratory suite for large-scale protein expression and purification in bacterial, insect and mammalian cells, together with state-of-the-art instrumentation for biophysical analysis, including an Analytical Ultracentrifuge, Differential Scanning and Isothermal Titration Calorimetry and stopped-flow fluorescence spectrometer for measurement of molecular size, shape, folded integrity, and thermodynamic and kinetic binding constants. The Resource directly supported Cancer Center investigator's work in the past funding period that led to the publication of at least 83 peer-reviewed papers, including 5 in Nature, Cell or Science, as well as more than 40 review articles on various aspects of structural biology and structure-function studies. Future priorities include the full integration of the crystallization robot facility into drug discovery efforts;additional instrumentation to measure binding kinetics of protein-small molecule interactions, and to measure mechanical forces within and between molecules and their interplay with chemical forces in processes such as cell migration;and further upgrades in eukaryotic protein expression and purification systems. Overall, $139,456 in CCSG support is requested in the first year, representing 12% of the total projected Structural Biology operating budget.

Public Health Relevance

Structural biology plays a central and critical role in many aspects of cancer research, from understanding the molecular bases of normal and aberrant cell behavior to the discovery and refinement of new inhibitors and probes. The Structural Biology Shared Resource provides expertise, training and sophisticated instrumentation that is well beyond the scope of individual laboratories but critical to their science.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA030199-32
Application #
8473823
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
32
Fiscal Year
2013
Total Cost
$208,397
Indirect Cost
$100,414
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Gong, Xiao-Min; Ding, Yi; Yu, Jinghua et al. (2015) Structure of the Na,K-ATPase regulatory protein FXYD2b in micelles: implications for membrane-water interfacial arginines. Biochim Biophys Acta 1848:299-306
Brun, S N; Markant, S L; Esparza, L A et al. (2015) Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma. Oncogene 34:3770-9
You, Weon-Kyoo; Yotsumoto, Fusanori; Sakimura, Kenji et al. (2014) NG2 proteoglycan promotes tumor vascularization via integrin-dependent effects on pericyte function. Angiogenesis 17:61-76
Vargas, Lina M; Leal, Nancy; Estrada, Lisbell D et al. (2014) EphA4 activation of c-Abl mediates synaptic loss and LTP blockade caused by amyloid-? oligomers. PLoS One 9:e92309
Volkmann, Niels; Page, Christopher; Li, Rong et al. (2014) Three-dimensional reconstructions of actin filaments capped by Arp2/3 complex. Eur J Cell Biol 93:179-83
Bailey, Ann M; Zhan, Le; Maru, Dipen et al. (2014) FXR silencing in human colon cancer by DNA methylation and KRAS signaling. Am J Physiol Gastrointest Liver Physiol 306:G48-58
Valencia, Tania; Kim, Ji Young; Abu-Baker, Shadi et al. (2014) Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis. Cancer Cell 26:121-35
Northcott, Paul A; Lee, Catherine; Zichner, Thomas et al. (2014) Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511:428-34
Kim, H; Claps, G; Moller, A et al. (2014) Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability. Oncogene 33:2004-10
Finlay, Darren; Vamos, Mitchell; Gonzalez-Lopez, Marcos et al. (2014) Small-molecule IAP antagonists sensitize cancer cells to TRAIL-induced apoptosis: roles of XIAP and cIAPs. Mol Cancer Ther 13:5-15

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