Zeiss LSM 980 Airyscan 2 Microscope for Shared Mental Health Research

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Project Summary/Abstract This proposal represents a request from a group of 6 NIMH-funded investigators with overlapping imaging needs for funding to acquire a shared Zeiss LSM980 Airyscan 2 confocal / super-resolution imaging platform to facilitate the visualization and quantification of the three-dimensional spatial organization of fixed cells and tissues as well as living specimens, with the latter including the need to monitor time-dependent changes. The system will be housed in the Washington University Center for Cellular Imaging (WUCCI), a shared technology resource at the School of Medicine. The current laser scanning confocal / super-resolution Airyscan microscopes in the WUCCI are already heavily subscribed and additional dedicated capacity is needed to facilitate the work of the NIMH- funded Major user projects described herein. The Zeiss LSM980 Airyscan 2 microscope platform is configured with (i) a Zeiss Axio Observer 7 inverted motorized microscope frame, (ii) 405 nm, 488 nm, 561 nm, and 639 nm excitation lasers, (iii) high-sensitivity PMTs, a 32-element spectral detector and a super-resolution Airyscan 2 detector, (iv) a variety of dry and immersion-based objective lenses and (v) a stage-top incubation system to facilitate the physiological imaging of living specimens. Six investigators from the Departments of Genetics and Neuroscience at the School of Medicine will make use of this imaging platform to enable a wide-range of studies aimed at investigating the genetic regulation of synapse-localized translation, the molecular mechanisms of gene regulation as well as the discovery and characterization of genetic etiological factors involved in Autism Spectrum Disorder (ASD), how mGluR5 mediated signal transduction is implicated in anxiety and depression and how loss of hippocampal activity leads to learning and memory deficits in cognitive disease. While the instrument has been configured to meet the specific needs of the NIMH major user group, we thoroughly expect it to impact many other research programs. The expertise and institutional support for this instrument are exceptional. Dr. James Fitzpatrick, the Scientific Director of WUCCI, and Dr. David Piston, the Chair of Cell Biology & Physiology and Chair of the WUCCI Advisory Board, are both world-renowned experts in cellular microscopy and their combined leadership brings over 40 years of experience in providing cost-efficient training and support for high- quality quantitative cellular imaging to a wide range of NIH-funded users. In support of this S10 grant application, the institution will also commit a total of $140,000 over five years to ensure the long-term success of this instrument.