This application requests funds to purchase a Miltenyi UltraMicroscope Blaze fluorescence light sheet microscope, to be included in the existing Integrated Cellular Imaging Core (ICIC). The primary goal of the ICIC is to provide investigators at Emory and surrounding Georgia institutions access to cutting edge light-based microscope technology, services, and expertise. This open shared resource has assisted 207 NIH grants held by 142 investigators in the last 5 FYs. Within the facility, the UltraMicroscope Blaze will be used to study an open and broad range of applications that bridge the gap from molecular level fluorescence specificity to systems level distributions and connectivity. Tissue clearing and light sheet imaging technology provide a high 3D resolution (~1 µm) across samples as large as 10 cm. From molecular level hormone distributions in neurological studies that span regions of an entire spiny mouse brain hemisphere (Kelly), to metastasis sites and their corresponding tumor microenvironments in whole mouse oncology (Lesinski), this relatively new microscopy technique provides a more complete picture than ever before. Further applications include 3D printing and bio fabrication investigations with direct clinical application for heart disease and brain development (Serpooshan), ophthalmological studies of retinal pigment epithelium cells and neurosensory connectivity in macular degeneration (Nickerson), 3D remodeling of intrahepatic bile ducts in liver injury (Gracz), and a combination of 3D pathology with single cell RNA transcriptomics in human intestine (Kugathasan). These case studies represent a small subset of the vast interest on Emory campus, and highlight the diversity and collaborative nature between institutions. An Emory/Georgia State University collaborating case study truly exemplifies the broad impact attainable from length scales encompassed by this light sheet microscope, detailing how novel molecular level metastatic regulators can be utilized in both MRI and fluorescence light sheet imaging, providing a unique, comprehensive, and longitudinal view of the key determinants of liver metastasis (Yang, GSU). The Miltenyi Blaze combines a unique balance of ease of use, flexibility, speed, together with the largest viable samples, thus providing researchers with expedited answers to their disease related longitudinal questions. This microscope will be managed as part of the facilities under the same stringent policies to ensure optimal usage and minimize downtime. The shared resources at Emory have a strong commitment marked by the largest set of core facility suites on Emory campus, housed in the soon to be completed 2nd Health Science Research Building (HSRB II), and the ICIC has a strong financial commitment from the School of Medicine and Winship Cancer Institute, including deficit coverage and supporting purchase funds. We feel the Miltenyi Blaze is an essential tool for addressing both current and future research ne...