Project Summary/Abstract We are requesting funds to support the purchase of a Zeiss LSM 980 Confocal Microscope with AiryScan2. This instrument will be housed within the Neuroscience Microscopy Core (NMC) at the University of North Carolina (UNC) School of Medicine. The mandate of this core facility is to provide a full spectrum of advanced systems for cellular and molecular imaging of fixed and live samples, to implement new imaging technologies, and to offer training, consultation, data analysis, image processing, and centralized technical expertise to support the imaging needs of UNC and other researchers. Confocal microscopy is an essential service provided by the center. The NMC currently has two 700-series Zeiss confocal microscopes, which constitute ~45% (over 4,000 hours of usage during FY 2020) of the facility’s annual hourly usage. Because Zeiss has announced that they will not be offering service contracts for the 700-series microscopes after 9/30/2022, we cannot rely upon these heavily-used instruments to maintain their current usage availabilities, and anticipate that they will become subject to more extended down-times. As there are an additional four 700-series confocal microscopes on campus that are heavily used and facing the same obsolescence cliff, investigators utilizing these microscopes will need access to a modern confocal to support their projects (see Letters of Support from Drs. Ariel, Perdue and Bear). Demand for confocal imaging at our Core will stay at and extend beyond capacity in order to maintain the current imaging needs for NIH-funded investigator’s research on campus. The need for this instrument is demonstrated in this application with several diverse NIH supported projects in fields including; Neurobiology, Cell Biology, Developmental Biology, Infectious Disease and Cancer Biology. We describe 8 NIH-funded projects that require the use of high-resolution optical sectioning provided by the AiryScan2, in order to distinguish fine cellular features with high spatial resolution within small or densely packed volumes (e.g., sites of RNA transcriptional activity inside the nucleus). Further, 9 NIH-funded PIs require increased speed of acquisition provided by the LSM 980 Confocal Microscope to acquire datasets with confocal spatial resolution (XYZ) over either large volumes (e.g., neuronal dendrites and axons in mouse brain tissue) or to measure rapid dynamics (e.g. dynamics and directionality of the neuronal growth cone, and intracellular dynamics of exosomes, mitochondria, and other cellular compartments and complexes). Since the NMC commenced operations 18 years ago, it has become an integral part of the medical research community currently supporting over 60 funded research projects. Acquisition of a Zeiss LSM 980 Confocal Microscope system is an essential addition to the repertoire of instrumentation available to NIH-funded investigators in order to not only maintain the current high-level of critical support fo...