This proposal requests support for a confocal microscope with state of the art features for multi-fluorescent protein studies, FRET imaging and electrophysiological studies. The Zeiss LCS 510 META confocal microscope will provide technology that is currently unavailable to and is pivotal for the research effort of eleven independent laboratories in the biomedical sciences. Research programs in all eleven laboratories are now at a critical phase where long term, reliable, and frequent access to this equipment is essential for further progress. All investigators are NIH-funded with research programs that include the following areas of investigation: mechanisms of ion channel and transporter function, synaptogenesis, structure and function of opioid receptors, signal transduction pathways in early embryonic development, calcium signaling in cardiac and vascular smooth muscle, the regulation of expression and localization of muscarinic acetylcholine receptors, stem cell repair of cardiac infarcts, bacterial pathogenesis and metabolism and cellular actions of cannabinoids in neurons. Although the research in these laboratories is primarily basic science in nature, it also has major and direct implications for numerous human diseases and maladies, including cardiac and vascular disease, cancer, muscular dystrophy, bacterial pathogenesis, defects of the visual system and drug addiction and abuse. The core investigators represent five separate departments in two schools. The broad range of projects proposed by the primary user group is representative of a larger group of potential users of the new microscope system. The requested instrument would be placed in the established Keck Imaging Facility located on the University of Washington campus and would be made available to other investigators when it is not being used by the core group of researchers. The operation and management of this equipment, the internal advisory committee and institutional support for the confocal microscope are described. The Keck Imaging Center and its director, Greg Martin, are widely known and valued at the University of Washington and its affiliated institutions, thus assuring that the new instrument and its state-of-the- art capabilities will have a broadly based clientele.
