DESCRIPTION (provided by applicant): We request funds to purchase a Zeiss LSM800 Confocal Microscope system with Airyscan to replace our 14 year old Zeiss/BioRad Radiance system that Zeiss can no longer guarantee to support or repair. The new instrument will be housed within the Program in Membrane Biology (PMB) Microscopy Core at the Massachusetts General Hospital (MGH) in the multidisciplinary Simches Research Center building. The mandate of this MGH approved Core facility is to provide access to a full range of techniques using microscopy and imaging to 2 NIH funded P30 Centers, Thematic Center members in the Simches building, and individual research groups within the MGH community and beyond. The PMB Core has developed considerable expertise in static and live cell imaging techniques that that been used by our extensive user base over the years. Our sophisticated imaging capabilities were enhanced 4 years ago by the incorporation of a Nikon A1R confocal platform to function alongside our older Zeiss Radiance, and together these instruments have been able to provide sufficient imaging bandwidth to serve our users. However, the Nikon is extensively used for longer term, live cell imaging, including FRET and FRAP experiments on live cells, while many of our users require instead consistent and timely access to a simpler confocal to perform more basic static imaging of fixed specimens. Unfortunately, we can no longer promise our many users that such access will continue after any given point in time, based on the fact that Zeiss can no longer guarantee to repair the Radiance. Therefore, the purpose of this application is: 1) To ensure that we can continue to provide routine confocal microscopy services to our extensive Core user base in the face of an old and potentially non repairable existing system; 2) To expand our Core capabilities to provide higher sensitivity and higher resolution (via the Airyscan detector) to our user base that will expand their imaging capabilities for exploring cellular details more precisely. The Airyscan detector provides a remarkable increase in resolution that is achieved easily and without the expense and specimen preparation issues that are associated with many other super resolution techniques. Since the PMB Core was founded in 1986, it has become a central part of the MGH/HMS medical research community. Over 37 NIH funded PIs and their numerous lab members within the HMS/MGH and in other institutions made significant user of the Core confocal in the past 12 months alone, and we have supported literally hundreds of peer review publications over the years. The Core has an ongoing quest to constantly improve and upgrade Core facilities in support of its user base. This has been achieved using funds from NIH SIG applications as well as considerable institutional support from the MGH leadership. Providing our Core users with continued access to an up to date fluorescence imaging platform is essential to maintaining the MGH community at the cutting edge of NIH funded, health related research.

PUBLIC HEALTH RELEVANCE: The use of sophisticated microscopes coupled with the development of new fluorescent molecules to prove cell function has revolutionized our understanding of how cells work and become defective in diseases, including kidney, heart, brain and lung disease. This application requests the purchase of a powerful microscope which uses lasers to understand how various proteins interact and function in different cell types.