Lightsheet microscopy is a technology that provides the ability to rapidly acquire millimeter-scale fluorescence image volumes at subcellular resolution, providing a practical solution to the challenge of fluorescence microscopy of large optically-cleared tissue samples. This is a proposal for funding to purchase an Alpenglow 3Di Open-Top-Lightsheet microscope system that would be installed, maintained and managed by the Indiana Center for Biological Microscopy, a core facility of the Indiana University School of Medicine, the Indiana University NIDDK U54 George M. O'Brien Center for Advanced Renal Microscopy and Molecular Imaging, the NIDDK-P30 Indiana Diabetes Research Center and the NIDDK-U54 Indiana Cooperative Center of Excellence in Hematology. The proposed system will be the first and only lightsheet microscope system available to all IU School of Medicine investigators, thus fulfilling a currently unmet need to support large-scale, high-resolution microscopy. The particular system has been chosen based upon an “open-top” design that is uniquely compatible with the slide-mounted samples used by the researchers described in the proposal, and a novel hybrid optical path that supports both high-speed, low resolution imaging as well as diffraction-limited high- resolution imaging. The system will be supported by matching funds obtained from the Department of Medicine and the Division of Nephrology that will be used to obtain additional equipment and support a technician to promote productive utilization of the system by users described in the proposal as well as future IU investigators. The new system will enable project investigators to conduct exciting and entirely new studies that will enhance their NIH-funded research and advance their goals to address serious issues in human health.