Core B: Multiscale Imaging and Proteomics Core
The Multiscale Imaging and Proteomics Core provides imaging of live animals, tissues, cells, and macromolecules coupled with protein characterization and quantitation services. The Core encompasses three umbrella technology thrusts: 1. Advanced multiscale imaging technology (headed by Dr. Ellisman); 2. Fluorescent reporters, indicators, and labels to monitor physiological and biochemical processes (headed by Dr. Tsien); and 3. Protein identification and quantitative proteomics (headed by Dr. Komives). This facility leverages the instrumentation and expertise of the National Center for Microscopy and Imaging Research (NCMIR) and the Biomolecular and Proteomics Mass Spectrometry Facility. These resources have been used to investigate the molecular mechanisms and the development of models that can be implemented to study the effects of exposure to superfund toxicants. The NCMIR is an NIH-supported National Biotechnology Research and Development Site, supported by NIH/NCRR and NIEHS. The NCMIR houses versatile, cutting-edge imaging technologies, including state-of-the-art computer workstations and digital display facilitates, enabling research projects to employ the most sophisticated and up-to-date imaging modalities. The collaboration between Dr. Tsien’s and Dr. Ellisman’s groups continues to develop and refine biological reagents and tools useful for molecular detection and monitoring of intracellular interactions. The Biomolecular and Proteomics facility has a long history of supporting SRP researchers particularly in the areas of LC/MSMS quantitation. It has expanded capabilities to include identification and quantitation (using iTRAQ) of large numbers of proteins and their post-translational modifications from complex mixtures. These imaging and proteomic technologies require expensive instrumentation, are constantly evolving and are practiced by highly specialized personnel. The Multiscale Imaging and Proteomics Core is vital to our program in two respects: (1) it provides advanced technology that enables sophisticated scientific imaging, protein analysis and data management at the frontiers of interdisciplinary work, and (2) it provides the capacity for the sharing of knowledge through science communication (e.g., Dr. Karin’s work and the March 2010 cover of Science showing the power of electron microscopy), which will help our Research Translation Core and Community Engagement Core meet its aims.
Scanning electron micrograph of Drosophila melanogaster that appeared on the cover of Science magazine (recorded by the UCSD SRP Imaging Core). Sestrins were shown to control ROS output and tissue damage.
Zhong, Z., Umemura, A., Sanchez-Lopez, E., Liang, S., Shalapour, S., Wong, J., He, F., Boassa, D., Perkins, G., Ali, S. R., McGeough, M. D., Ellisman, M. H., Seki, E., Gustafsson, A. B., Hoffman, H. M., Diaz-Meco, M. T., Moscat, J., Karin, M. (2016) NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria. Cell. 2016 Feb 25;164(5):896-910. doi: 10.1016/j.cell.2015.12.057.
Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress. (2015) Antonucci, L., Fagman, J. B., Kim, J. Y., Todoric, J., Gukovsky, I., Mackey, M., Ellisman, M. H., Karin, M. Proc Natl Acad Sci U S A. 112(45), E6166-74. doi: 10.1073/pnas.1519384112.
Dowding, J. M., Song, W., Bossy, K., Karakoti, A., Kumar, A., Kim, A., Bossy, B., Seal, S., Ellisman, M. H., Perkins, G., Self, W. T., Bossy-Wetzel, E. (2014) Cerium oxide nanoparticles protect against Aβ-induced mitochondrial fragmentation and neuronal cell death. Cell Death. Differ. 21(10), 1622-32.
Pamenter, M. E., Perkins, G. A., Gu, X. Q., Ellisman, M. H., Haddad, G. G. (2013) DIDS (4,4-diisothiocyanatostilbenedisulphonic acid) induces apoptotic cell death in a hippocampal neuronal cell line and is not neuroprotective against ischemic stress. PLoS One. 10.1371/journal.pone.0060804.
Perkins, G. A., Scott, R., Perez, A., Ellisman, M. H., Johnson, J. E., Fox, D. A.. (2012) Bcl-xL-mediated remodeling of rod and cone synaptic mitochondria after postnatal lead exposure: electron microscopy, tomography and oxygen consumption. Mol Vis. 18, 3029-48
Lee, J. H., Budanov, A. V., Talukdar, S., Park, E. J., Park, H. L., Park, H. W., Bandyopadhyay, G., Li, N., Aghajan, M., Jang, I., Wolfe, A. M., Perkins, G. A., Ellisman, M., Bier, E., Scadeng, M., Foretz, M., Viollet, B., Olefsky, J., Karin, M. (2012) Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab.16(3), 311-21.
Falivelli, G., De Jaco, A., Favaloro, F. L., Kim, H., Wilson, J., Dubi, N., Ellisman, M. H., Abrahams, B. S., Taylor, P., Comoletti, D. (2012) Inherited genetic variants in autism-related CNTNAP2 show perturbed trafficking and ATF6 activation. Hum Mol Genet. 21(21), 4761-73.
Jobe, T. O., Sung, D. Y., Akmakjian, G., Pham, A., Komives, E. A., Mendoza-Cózatl, D. G., Schroeder, J. I. (2012) Feedback inhibition by thiols outranks glutathione depletion: a luciferase-based screen reveals glutathione-deficient γ-ECS and glutathione synthetase mutants impaired in cadmium-induced sulfate assimilation. Plant J. 70(5), 783-95. doi: 10.1111/j.1365-313X.2012.04924.x.
De Jaco, A., Lin, M. Z., Dubi, N., Comoletti, D., Miller, M. T., Camp, S., Ellisman, M., Butko, M. T., Tsien, R. Y., Taylor, P. (2010) Neuroligin trafficking deficiencies arising from mutations in the alpha/beta-hydrolase fold protein family. J Biol Chem. 285(37), 28674-82.
Lee, J. H., Budanov, A. V., Park, E. J., Birse, R., Kim, T. E., Perkins, G. A., Ocorr, K., Ellisman, M. H., Bodmer, R., Bier, E., Karin, M. (2010) Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science. 327(5970),1223-8. doi: 10.1126/science.1182228.
Yamaguchi, R., Lartigue, L., Perkins, G., Scott, R. T., Dixit, A., Kushnareva, Y., Kuwana, T., Ellisman, M. H., (2008) Newmeyer DD.Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization. Mol Cell. 31(4), 557-69.
Pezzoli, K., Tukey, R., Sarabia, H., Zaslavsky, I., Miranda, M. L., Suk, W. A., Lin, A., Ellisman, M. (2007) The NIEHS Environmental Health Sciences Data Resource Portal: placing advanced technologies in service to vulnerable communities. Environ Health Perspect. 115(4), 564-71. doi: 10.1289/ehp.9817
Bencheikh-Latmani, R., Obraztsova, A., Mackey, M. R., Ellisman,M. H., Tebo, B. M., (2007) Toxicity of Cr(lll) to Shewanella sp. strain MR-4 during Cr(VI) reduction. Environ Sci Technol. 41(1), 214-20.
Shi, J., Koeppe, J. R., Komives, E. A., Taylor, P., (2006) Ligand-induced conformational changes in the acetylcholine-binding protein analyzed by hydrogen-deuterium exchange mass spectrometry. J Biol Chem. 281(17), 12170-7.
De Jaco, A., Comoletti, D., Kovarik, Z., Gaietta, G., Radic, Z., Lockridge, O., Ellisman, M. H., Taylor, P. A., (2006) mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein family. J Biol Chem. 281(14), 9667-76.
Comoletti, D., De Jaco, A., Jennings, L. L., Flynn, R. E., Gaietta, G., Tsigelny, I., Ellisman, M. H., (2004) Taylor P.The Arg451Cys-neuroligin-3 mutation associated with autism reveals a defect in protein processing. J Neurosci. 24(20), 4889-93
Dooley, C. T., Dore, T. M., Hanson, G. T., Jackson, W. C., Remington, S. J., Tsien, R. Y., (2004) Imaging dynamic redox changes in mammalian cells with green fluorescent protein indicators. J. Biol. Chem. 279(21), 22284-93.
Jennings, L. L., Malecki, M., Komives, E. A., Taylor, P., (2003) Direct analysis of the kinetic profiles of organophosphate-acetylcholinesterase adducts by MALDI-TOF mass spectrometry. Biochemistry. 42(37), 11083-91.
Middleton, S. S., Latmani, R. B., Mackey, M. R., Ellisman, M. H., Tebo, B. M., Criddle, C.S. (2003) Cometabolism of Cr(VI) by Shewanella oneidensis MR-1 produces cell-associated reduced chromium and inhibits growth. Biotechnol Bioeng. 83(6), 627-37.
He, L., Perkins, G. A., Poblenz, A. T., Harris, J. B., Hung, M., Ellisman, M. H., Fox, D. A., (2003) Bcl-xL overexpression blocks bax-mediated mitochondrial contact site formation and apoptosis in rod photoreceptors of lead-exposed mice. Proc Natl Acad Sci USA. 100(3),1022-7
Main Contact Information
- Dr. Mark H. Ellisman
- Dr. Elizabeth A. Komives
- Dr. Roger Y. Tsien
Superfund Related Core Members:
- Guy Perkins
- Majid Ghassemian
- Hiroyuki Hakozaki
- Mason Mackey
UCSD Superfund Research Center
University of California, San Diego
9500 Gilman Drive, Mail Code 0722
La Jolla, CA 92093-0722