Multiscale Imaging and Proteomics Core

Core B: Multiscale Imaging and Proteomics Core

Summary

​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

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.

Publication

PubMed Central ID: 

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

PubMedID: 26919428
PubMed Central ID: 

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.

PubMedID: 26512112
PubMed Central ID: 

Engineer, C. B., Ghassemian, M., Anderson, J. C., Peck, S. C., Hu, H., Schroeder, J. I. (2014) Carbonic anhydrases, EPF2 and a novel protease mediate CO2 control of stomatal development. Nature. 513(7517), 246-50.

PubMedID: 25043023
PubMed Central ID: 

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.

PubMedID: 24902900
PubMed Central ID: 

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.

PubMedID: 23577164
PubMed Central ID: 

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

PubMedID: 23288995
PubMed Central ID: 

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.

PubMedID: 22958918
PubMed Central ID: 

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.

PubMedID: 22872700

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.

PubMedID: 22283708
PubMed Central ID: 

Suhr, S. T., Chang, E. A., Tjong, J., Alcasid, N., Perkins, G. A., Goissis, M. D., Ellisman, M. H., Perez, G. I., Cibelli, J. B. (2010) Mitochondrial rejuvenation after induced pluripotency. PLoS One. doi: 10.1371/journal.pone.0014095.

PubMedID: 21124794
PubMed Central ID: 

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.

PubMedID: 20615874
PubMed Central ID: 

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.

PubMedID: 20203043
PubMed Central ID: 

Perkins, G., Bossy-Wetzel, E., Ellisman, M. H., (2009) New insights into mitochondrial structure during cell death. Exp Neurol. 218(2), 183-92.

PubMedID: 19464290
PubMed Central ID: 

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.

PubMedID: 18691924
PubMed Central ID: 

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.

PubMedID: 17450225

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.

PubMedID: 17265950

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.

PubMedID: 16484218

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.

PubMedID: 16434405

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

PubMedID: 15152050

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.

PubMedID: 14985369

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.

PubMedID: 12974645

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.

PubMedID: 12889027
PubMed Central ID: 

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

PubMedID: 12540825

Main Contact Information

Core Leader

  • Dr. Mark H. Ellisman

Mark H. Ellisman, Ph.D., Core Leader
University of California, San Diego
Neuroscience Department
9500 Gilman Drive BSB, m/c 0608
La Jolla, CA 92093-0608
P: 858-534-2251 F: 858-534-7497
E-mail: mellisman@ucsd.edu

Elizabeth A. Komives, Ph.D., Core Co-Leader
University of California, San Diego
Department of Chemistry and Biochemistry
9500 Gilman Drive NSB
4324 La Jolla, CA 92093-0378
P: 858-534-3058 F: 858-534-6174
E-mail: ekomives@ucsd.edu

Roger Y. Tsien, Ph.D., Core Co-Leader
University of California, San Diego
Department of Chemistry & Biochemistry and Pharmacology
9500 Gilman Drive CMME, Mailcode 0647
La Jolla, CA 92093-0647
P: 858-534-4891 F: 858-534-5270
E-mail: rtsien@ucsd.edu

Contact

UCSD Superfund Research Center
University of California, San Diego
Pharmacology Department
9500 Gilman Drive, Mail Code 0722
La Jolla, CA 92093-0722