Seattle Children's Shared Light Sheet Microscopy Facility - PROJECT SUMMARY The goal of this application is to provide biomedical researchers at the Seattle Children’s Research Institute (SCRI), University of Washington (UW) and other partner institutions in the Seattle area with a new light-sheet microscopy system (LifeCanvas Technologies SmartSPIM) to image tissue structure from whole organism scale to microscopic resolution. The requested equipment will support a diversity of basic and translational studies headed by leaders in their respective fields, with projects tackling neurodevelopmental disorders, cancer biology, developmental biology, stem cells and tissue regeneration, and vascular biology. This imaging resource will support the activities of 13 major users and 4 minor users supported by a portfolio of 24 NIH grants, as well as funding from other federal agencies and foundations. This exciting new technology will allow researchers to obtain broader and holistic data sets that will improve the quality of data collected and accuracy of the results. It will allow researchers to overcome technical limitations of conventional 2-D histology, which fails to capture the 3-D architecture of vascular networks, the localization of cellular subpopulations and connectivity of neural circuits. Further, some projects involve the use of delicate tissue preparations or lightly adherent cell types that will be affected by handling/processing of thin tissue sections. Our application is supported by ample pilot data demonstrating need for the equipment and expertise in performing light-sheet imaging and image analysis. There is strong Institutional commitment for the instrument, including state-of- the-art imaging space, coverage of service contracts, maintenance personnel effort in at least the first 5 years, backed-up data storage, and 3-D image analysis resources. This imaging resource would immediately influence the productivity and innovation of ongoing work and will be critical in furthering the long-range objectives of the biomedical community at SCRI and in the greater Seattle area.