? STRUCTURAL BIOLOGY SHARED RESOURCE The mission of the Structural Biology Shared Resource is to advance our understanding of the molecular basis of cancer by giving Cancer Center scientists access to equipment, technology and expertise for structural and biophysical studies of biological molecules. Structural biology enables multi-scale visualization of molecular and supramolecular structure and dynamics with the ultimate goal of characterizing biological systems in their functional native states. This requires a multidisciplinary approach that spans the ranges of length and time scales effective in biology. The Core, managed by the Center, maintains state-of-the-art equipment, develops technology, provides service, and promotes collaborative activities with Cancer Center scientists. There are four central and complementary areas of structural biology: nuclear magnetic resonance (NMR), X-ray crystallography, the recently added electron cryo-microscopy and cellular tomography (cryo-EM, and ET), and the long-standing biomolecular analysis facility. These technologies are typically not available in individual Center member laboratories, owing to their expense and complexity of operation. Core equipment supporting NMR includes two 600 MHz instruments with cryoprobes, a wide bore 500 MHz spectrometer set up for solid state analysis, and a highly automated 400 MHz instrument supporting chemistry. X-ray crystallography equipment includes a robotic dispenser and two, automated imaging incubators (5 and 20), a Rigaku FRE SuperBright X-ray diffractometer with two independent beams and detectors. Cryo-EM analysis is supported by a Thermo Titan Krios with a 4Kx4K Falcon III direct electron detection device and a phase plate, as well as a Tecnai 12 Spirit G2 equipped with a 4Kx4K CCD. Finally, equipment supporting biomolecular analysis includes an analytical ultracentrifuge, DSC, UV/vis spectrometry, Fluorescence spectrophotometer, two ITC instruments, and MST. The three Ph.D.-level Core staff maintain the equipment, train users, and in the case of biomolecular analysis, provide full-service analysis. For structural biology analysis, Core users can collaborate with Core staff for smaller projects or collaborate with expert structural biology groups in the Cancer Center to pursue more complex projects. A number of such successful collaborations are described in the Research Plan. In the past 5 years, the Core was used by 16 Center labs representing all three programs, and supported 62 cancer-related publications.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA030199-39
Application #
9934920
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2020-05-27
Budget End
2021-04-30
Support Year
39
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Sanford Burnham Prebys Medical Discovery Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Ekanayake, Vindana; Nisan, Danielle; Ryzhov, Pavel et al. (2018) Lipoprotein Particle Formation by Proapoptotic tBid. Biophys J 115:533-542
Diez-Cuñado, Marta; Wei, Ke; Bushway, Paul J et al. (2018) miRNAs that Induce Human Cardiomyocyte Proliferation Converge on the Hippo Pathway. Cell Rep 23:2168-2174
Wang, Yang; Li, Yue; Yue, Minghui et al. (2018) N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nat Neurosci 21:195-206
Lundquist, Mark R; Goncalves, Marcus D; Loughran, Ryan M et al. (2018) Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid Metabolism By Facilitating Autophagy. Mol Cell 70:531-544.e9
Ramirez, Monica L Gonzalez; Poreba, Marcin; Snipas, Scott J et al. (2018) Extensive peptide and natural protein substrate screens reveal that mouse caspase-11 has much narrower substrate specificity than caspase-1. J Biol Chem 293:7058-7067
Wei, Yang; Toth, Julia I; Blanco, Gabrielle A et al. (2018) Adapted ATPase domain communication overcomes the cytotoxicity of p97 inhibitors. J Biol Chem 293:20169-20180
Tinoco, Roberto; Carrette, Florent; Henriquez, Monique L et al. (2018) Fucosyltransferase Induction during Influenza Virus Infection Is Required for the Generation of Functional Memory CD4+ T Cells. J Immunol 200:2690-2702
Wonder, Emily; Simón-Gracia, Lorena; Scodeller, Pablo et al. (2018) Competition of charge-mediated and specific binding by peptide-tagged cationic liposome-DNA nanoparticles in vitro and in vivo. Biomaterials 166:52-63
Limpert, Allison S; Lambert, Lester J; Bakas, Nicole A et al. (2018) Autophagy in Cancer: Regulation by Small Molecules. Trends Pharmacol Sci 39:1021-1032
Fujita, Yu; Khateb, Ali; Li, Yan et al. (2018) Regulation of S100A8 Stability by RNF5 in Intestinal Epithelial Cells Determines Intestinal Inflammation and Severity of Colitis. Cell Rep 24:3296-3311.e6

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