Multipurpose Upright Optical Microscope for Imaging Core - Abstract Funds are requested to acquire a Zeiss LSM 900 fluorescence confocal microscope to support the research efforts of multiple NIH-funded investigators at the Virginia Commonwealth University (VCU). The microscope will meet increasing demand multicolor 3D imaging of cell cultures and tissue samples in automated manner. Numerous research questions, developed in recent years, require visualization of these specimens at multiple scales, from cell population down to subcellular structures (vesicles, endoplasmic reticulum tubules, cytoskeletal filaments). None of the microscopes currently available at VCU (confocal or structured illumination) have the combination of imaging speed, ease of magnification changes and ergonomic operation, needed to execute these tasks robustly for large number of samples. The requested Zeiss system is configured around an Axio Imager Z2 upright stand and equipped with a motorized (piezo) stage with a 4-slide holder. The microscope has 3 high-sensitivity fluorescence confocal detectors, a transmitted light detector and a color camera for wide-field imaging. These features will make the LSM 900 a significant upgrade of the only upright VCU confocal microscope, Zeiss LSM 700 and its wide-field counterpart, Zeiss/MBF Neurolucida. The former system has experienced heavy usage since its installation in 2013. However, performance of the LSM 700 no longer meets requirements of contemporary experimental protocols and its further maintenance no longer guaranteed by the manufacturer (Zeiss). The new system will be housed in a well-established and highly productive Microscopy Shared Resource (MSR) facility. MSR is directed by the PI, who has expertise in multiple aspects of microscopic imaging. During the past five years (2019 - 2023), 135 different laboratories, representing 312 investigators from 17 different departments at VCU have used the MSR and its services (widefield fluorescence, confocal, TIRF, SIM, electron microscopy, image analysis, and sample preparation). The projects conducted by these researchers represent a broad range of studies (cell biology, microbiology, neurobiology, bioengineering, virology, pharmacology, physiology, etc.). Representative studies of major users (from 12 labs; 5 departments) and minor users (from 3 labs; 2 departments), who are funded by NIH, have been highlighted in this proposal. Acquisition of a versatile confocal/wide-field microscope will have a major impact on research at VCU as it will preserve and expand the capacity of a well-used core facility and attract additional users (whose needs cannot be met by the equipment available at VCU).