PROJECT SUMMARY: Cell and Tissue Imaging Core A Advanced cellular microscopy is a powerful tool for biological research and has an important role to play in the study of the pathogenesis and eventual treatment of human diseases. Imaging technology has evolved rapidly over the last decade leading to improvements in resolution, sensitivity and speed which have created fundamentally new opportunities for studying processes across many orders of magnitude and in real-time in living cells and organisms. The Cell and Tissue Imaging Core A is comprised of a shared cutting-edge multi-scale microscopy facility that is essential to the research goals of the 3 projects in this P01 renewal application entitled “New Therapies for liver fibrosis and hyperproliferation in alpha1-AT deficiency (ATD)”. The facility is housed within the Washington University Center for Cellular Imaging (WUCCI) (http://wucci.wustl.edu), to leverage recent significant institutional investments at Washington University School of Medicine as well as to provide an integrated approach to investigating the structure and dynamic behavior of ATD specific cells and tissues. All projects within this P01 renewal plan to make heavy use of the diverse array of cellular microscopy approaches available in the WUCCI. Methodologies available to project PIs include optical microscopy modalities such as fluorescence microscopy, confocal and two- photon microscopy, live-cell microscopy (both confocal and Total Internal Reflection - TIRF), super- resolution microscopy (both PALM / STORM and SIM) and slide-scanning microscopy (both bright-field and fluorescence). Additional advanced fluorescence modalities such as FRET, FRAP, spectral and ratiometric imaging are also available. A complete array of ultrastructural approaches is also available to project investigators. These comprise both transmission and scanning electron microscopy (TEM and SEM), negative staining, traditional thin section EM, immuno-EM, serial block face Focused Ion Beam-SEM (FIB- SEM), X-ray microscopy, single particle cryo-EM and cryo-Electron Tomography (ET). Furthermore, the facility provides access to a wide range of image analysis and quantitation software as well as technical assistance in their appropriate use from facility staff. Since the facility, the equipment and the staff expertise reside in one contiguous location, seamless integration between the imaging modalities can be realized. The facility is accessible ID card 24/7 by trained users who can also book instrument time or submit sample- processing requests anytime through our on-line web-based e-management solution, Agilent CrossLab (formerly iLab solutions).