The objective of the C-SiG Optical Microscopy Core, is to be a state-of-the-art, user-friendly service that connects investigators with the many optical technologies and applications at a reasonable cost. Under the direction of Dr. Mark McNiven, a well-established cell biologist, the Core integrates existing resources from the Mayo Microscopy and Cell Analysis Core and from individual investigators in the Division of Gastroenterology and Hepatology (GIH) as well as providing additional new technologies not previously available.
The Specific Aims of this core are three-fold. First, to provide reliable, accessible, state-of-the-art microscopic technology to all C-SiG members that will facilitate their study of Gl cellular signaling cascades. Second, to educate and train C-SiG members;in the use of both basic and sophisticated cellular imaging methods. Emphasis is placed on providing technical instruction as well as educating faculty on how such approaches can expand the scope and breadth of their scientific programs. Third, to develop and apply state-of-the-art optical imaging technologies, including fluorescent probes and biosensors, to study Gl tissues and/or cells. The most popular Core service is access to the well-maintained C-SiG Confocal Microscopes. The Core also provides instruction, technical advice, data interpretation, and development of novel, innovative optical approaches to the study of signaling pathways in Gl cells and tissues. These services cover a wide range of topics including: real-time computer/video imaging of live cells;confocal microscopy coupled with computer-based 3-D image reconstruction;Fluorescence Resonance Energy Transfer (FRET) applications to measure dynamic protein-protein interactions;Fluorescence Recovery After Photobleaching (FRAP) that allows the quantitation of protein recruitment/turnover;Fluorescence Loss in Photobleaching (FLIP);microinjection of living cells;expression and use of fluorescence-based bioprobes that facilitates the study and localization of specific signaling molecules including both proteins and lipids;the development and application of specific photo-activatable caged-compounds that allow a precise temporal and spatial activation of desired signaling molecules in live cells;Total internal reflection (TIRF) microscopy; multiphoton microscopy, and super-resolution microscopy. Core services have been used by 58% of CSiG members and supported 106 publications.

Public Health Relevance

Gastrointestinal diseases and their complications have a significant effect on public health and health care utilization costs. The C-SiG Optical Microscopy Core supports scientific advancements of C-SiG members that are critically important for furthering understanding of the mechanisms that underlie digestive diseases, which can lead to practical applications for the diagnosis, prevention, monitoring and treatment of human disease.

National Institute of Health (NIH)
Center Core Grants (P30)
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Special Emphasis Panel (ZDK1)
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Mayo Clinic, Rochester
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Yang, Liu; Kwon, Junghee; Popov, Yury et al. (2014) Vascular endothelial growth factor promotes fibrosis resolution and repair in mice. Gastroenterology 146:1339-50.e1
Guenzel, Adam J; Hillestad, Matthew L; Matern, Dietrich et al. (2014) Effects of adeno-associated virus serotype and tissue-specific expression on circulating biomarkers of propionic acidemia. Hum Gene Ther 25:837-43
Bi, Yan; Mukhopadhyay, Dhriti; Drinane, Mary et al. (2014) Endocytosis of collagen by hepatic stellate cells regulates extracellular matrix dynamics. Am J Physiol Cell Physiol 307:C622-33
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Peng, Ying; Clark, Karl J; Campbell, Jarryd M et al. (2014) Making designer mutants in model organisms. Development 141:4042-54
Yaqoob, Usman; Jagavelu, Kumaravelu; Shergill, Uday et al. (2014) FGF21 promotes endothelial cell angiogenesis through a dynamin-2 and Rab5 dependent pathway. PLoS One 9:e98130
Koh, Kwi Hye; Pan, Xian; Zhang, Wei et al. (2014) Kr├╝ppel-like factor 9 promotes hepatic cytochrome P450 2D6 expression during pregnancy in CYP2D6-humanized mice. Mol Pharmacol 86:727-35
Razumilava, Nataliya; Gradilone, Sergio A; Smoot, Rory L et al. (2014) Non-canonical Hedgehog signaling contributes to chemotaxis in cholangiocarcinoma. J Hepatol 60:599-605
Bhat, Mamatha; Chaiteerakij, Roongruedee; Harmsen, William S et al. (2014) Metformin does not improve survival in patients with hepatocellular carcinoma. World J Gastroenterol 20:15750-5
Tabibian, James H; O'Hara, Steven P; Splinter, Patrick L et al. (2014) Cholangiocyte senescence by way of N-ras activation is a characteristic of primary sclerosing cholangitis. Hepatology 59:2263-75

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