Project Summary The School of Medicine’s Light Microscopy Imaging Core (SOM-LMIC) at Case Western Reserve University requests funding for a Zeiss Lightsheet 7 microscope, which would have an enormous benefit to our active research community. Currently, the Cleveland area does not have a commercial light-sheet microscope (LSM) available to its researchers. This is particularly surprising considering the excitement and increased use of LSM. Obtaining this imaging system would allow us to continue to provide state-of-the-art imaging to our expanding user base. The Zeiss Lightsheet 7 provides several advantages that our current instrumentation cannot provide, allowing our current users to ask new questions as well as attracting new projects we currently cannot support. First, the system enables one to acquire cellular resolution over sizeable fields of view. Many of our users have struggled to assess the spatial extent of molecular changes over larger regions (e.g., entire brain region, throughout embryonic heart, prostate biopsy, etc.). Second, the Zeiss Lightsheet 7 has much higher acquisition rates than standard confocal microscopy. Because an entire sheet is collected in comparison to point by point for confocal, the acquisition rates are much higher. This will benefit all of our users by enabling them to either save time, realistically image larger samples for a study, or provide higher temporal resolution for live imaging. Third, several of our users have problems with photobleaching or phototoxicity (e.g., live imaging applications). The Zeiss Lightsheet 7 only illuminates tissue that is being imaged which greatly reduces the required light levels and photobleaching/phototoxicity compared to confocal microscopy. The Zeiss Lightsheet 7 will ensure the continued success of many NIH-funded programs at CWRU and nearby institutions. For this proposal, we have identified 10 major and 4 minor users. This imaging system will allow our users to make contributions to a diverse number of fields including developmental biology (Atit, Bearer, Jenkins, Ward), 3D histopathology (Gupta, Madabhushi), virology (Levine), otolaryngology (McDermott), subcellular dynamics (Mears, Kisley), cardiology (Rollins), neurology (Tesar, Pieper), and clinical applications of microfluidics (Gurkan). We anticipate that this instrument will foster collaborations within our user groups and that other users will benefit from this resource especially after they become aware of its potential. Without the Zeiss Lightsheet 7 many of the projects described in this proposal will not be possible. As one of Case Western Reserve University’s 11 Institutional Core Facilities, significant investment into administration and infrastructure has been made to support our daily operations. To support the long-term operation of this instrument, the University has agreed to further contribute nearly 130k. The requested Zeiss Lightsheet 7 is essential to the needs of our evolving research, clinical ...