Three-dimensional imaging of cells and tissues with ultrahigh spatiotemporal resolution by lattice light sheet microscopy

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Resolving the highly dynamic organization of biomolecules into functional units is the key to mechanistic understanding of biological processes. With its compatibility with life cell imaging, its very high sensitivity and selectivity as well as its versatile tools and reporters to probes mo-lecular and cellular functions, fluorescence microscopy offers unique possibilities to tackle this challenge. Overcoming the diffraction limited resolution by different so-called superresolution imaging techniques has stimulated tremendous developments in fluorescence microscopy of molecular processes in cells. At the Biology Department of the University of Osnabrück, these exciting developments were early on taken up to tackle fundamental cell biological questions in very different biological context. Supported by the expertise of the Division of Biophysics, we fo-cused on single molecule localization-based imaging techniques that we felt were most suitable to unravel the spatiotemporal dynamics of molecular processes in living cells. These efforts are fostered and coordinated by a joint research initiative, the Collaborative Research Center 944 “Physiology and Dynamics of Cellular Microcompartments” that took off in 2011. Currently, nine groups from Osnabrück and four groups from Münster collaborate in this CRC from different bio-logical perspectives on the overarching question how biomolecules in cells dynamically self-organize into functional microcompartments. Important asset of this CRC is a dedicated advanced light microscopy facility that we established during its first funding period. Close interfacing of method development and application to highly diverse biological problems and model systems has yielded a unique expertise in live cell single molecule localization microscopy.