A.3.I. Molecular Imaging Reporter Core (MIRC)The Molecular Imaging Reporter Core is a central facility providing expertise, materials andcollaborative assistance for design and execution of biological aspects of molecular imaging. If one was toidentify the one Core that represented the essence of ICMIC innovation at Washington University, it wouldbe the Molecular Imaging Reporter Core. The MIRC serves investigators possessing a wide range ofresources and experience in molecular biology, cell culture, and animal experimentation. One of the mostimportant activities of this core is discovery research and dissemination of our novel molecular imagingreagents and genetically-encoded reporters to investigators within our institution, to other P50 program sitesand to cancer biology and imaging investigators throughout the world. Discovery research in this Coreprovided the research community with: 1) Novel PET- and bioluminescence-based reporters of proteinproteininteractions in vivo based on modified two-hybrid transcriptional strategies, 2) Novel firefly luciferaseprotein fragment complementation strategies for real-time imaging of protein-protein interactions in vivo, 3)Novel fusion protein strategies for imaging proteasome function in vivo, 4) Innovative platform strategies tointerrogate ubiquitin-induced degradation of ligand-regulated proteins in signaling pathways in real time(e.g., kB, p-catenin and Cdc25A), 5) Second generation fusion reporters and triple-modality reporters formulti-modality imaging (PET/bioluminescence/ fluorescence), 6) Engineered convenient vectors for cloningand expression of click beetle luciferases, firefly luciferase, Renilla luciferase, mtHSV1-TK, mtSSTR-2 andothers for a variety of imaging applications, and 7) Production of transgenic and knock-in molecular imagingreporter mice (e.g., Gal4-Fluc, p21-Fluc, ROSA26-LSL-CGR-mGFP).Indeed, this Core has been and continues to be one of our most productive andcomprehensive activities, discovering and developing novel reporters and impacting a broad rangeof research programs throughout the world. Many investigators within the Washington Universitycommunity as well as outside institutions have directly received material and support from the WU MIRCduring the 5 year period covered by the progress report. These activities include new initiatives,continuation collaborative projects as well as pilot projects that now extend our reach far beyond the focusof the original projects proposed for the Center Program. Overall, as of June 2006, we have distributed ourcollection of molecular imaging reporter reagents and cells to dozens of WU investigators as well as 86investigators throughout the world. Several other P50 ICMIC institutions have requested and received ourcells and reagents, including investigators at the Johns Hopkins University ICMIC (split firefly luciferase,Ub-FLuc plasmid, IkB-FLuc and control plasmids); investigators at the Stanford University ICMIC (IkB-FLuc,FLuc vectors, stable reporter cells expressing IkB-FLuc, coelenterazine analogues); investigators at theUniversity of Michigan ICMIC (split firefly luciferase, Ub-FLuc plasmid); and investigators at Harvard (splitfirefly luciferase, IkB-FLuc). Our most popular reagents (implying high impact) include plasmids encodingour luciferase complementation fragments (split luciferase), IkB-firefly luciferase fusion construct, polyubiquitinated-firefly luciferase, mutant NLS-sr39HSV1-TK-EGFP fusion reporter, and Gal4-firefly luciferasereporter. Publications in high profile journals (e.g., PNAS 2006, 103:1313-1318) have already appeared inthe literature citing us as the source of these molecular imaging reagents for their respective projects.
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