Acquisition of a Zeiss Lightsheet 7 Fluorescence Microscope for UT Austin Microscopy Core - PROJECT SUMMARY We request funds for a Zeiss Lightsheet 7 microscope for the Microscopy and Flow Cytometry (MFC) Facility at the University of Texas at Austin. The MFC is a centralized core facility used annually by over 500 researchers in 130 labs across 24 departments and 5 colleges. While the UT Austin campus offers several advanced microscopes, there is no shared light sheet microscope. With this microscope, exciting research approaches will be enabled for 17 investigators with 29 NIH-sponsored projects. Light sheet microscopes acquire large volumes quickly. A thin sheet of light is created by illumination objective(s) that are decoupled from the detection objective(s). A lower numerical aperture illumination lens creates the thin excitation sheet across the entire focal plane, and a higher numerical aperture objective resolves small features. Use of a camera allows fast capture with the inherent optical sectioning. Other microscopes risk sample damage from laser exposure, loss of fluorescence from photobleaching, and scattering artifacts deeper into a sample. When high resolution is needed or to image thin samples, our researchers have access to a suite of confocal microscopes, multiphoton microscopes, spinning disk, TIRF, and super resolution microscopes. But for rapid, 3D imaging, we do not have the right tool, a light sheet microscope. Developmental biology and neuroscience researchers, in particular, need light sheet microscopy. Many of our researchers use small, living organisms to investigate eye disease and injury, scoliosis and spinal development, spina bifida and other birth defects, and mitochondrial disorders. Others use mouse models to study brain disorders and will use a variety of clearing techniques to make large tissues transparent for even deeper light penetration. These users study strokes, motor control, Parkinson’s, substance abuse, and bipolar disorder. The third cohort of our group uses 3D cell constructs and organoids to model physiological tissues and study therapeutics in vitro. For all these samples, imaging is currently time-consuming, arduous, or impossible. The Zeiss Lightsheet 7 was designed for living samples, most of our imaging needs, but with large chambers and long working distance objectives, it can also image cleared organisms and tissues. To serve a world-class, multidisciplinary research institution, we chose the Zeiss because of its versatility and image quality. Our faculty have long wanted this technology, and our institution has committed funds to purchase service contracts, providing long-term sustainability. With this level of support, the need and enthusiasm of our users, and the care of the MFC, the Zeiss Lightsheet 7 will have transformative impact on current and future biomedical research at UT Austin.