Light-sheet fluorescence microscopy has emerged as a powerful imaging technique that provides exceptionally high imaging speed and high spatial resolution while minimizing the amount of light energy used to interrogate the specimen. This combination of capabilities makes light-sheet microscopy indispensable for developmental and functional in vivo imaging of complex biological systems with high spatio-temporal resolution.
We are developing advanced implementations of light-sheet microscopy, such as our SiMView, hs-SiMView, and IsoView microscopes for simultaneous multi-view imaging of large living specimens, and are further enhancing these instruments by adaptive imaging techniques for improving spatial resolution and automating complex imaging experiments. We are using these methods to systematically reconstruct whole-embryo development in multiple model systems (fruit fly, zebrafish, and mouse) at the single-cell level and to perform high-resolution functional imaging of the entire early nervous system.
Complementing these imaging techniques, we are developing strategies for automated, efficient and robust image processing of the resulting large-scale microscopy data sets, including methods for multi-view data processing, cell segmentation, and cell tracking. This combined experimental and computational framework allows us to quantitatively analyze neuronal activity across the nervous system of behaving animals, systematically extract developmental lineages and their interrelationships at the system level, and link this developmental building plan to emerging functional properties of the early nervous system.