Enabling Live-Cell Super Resolution Imaging Through Lattice Light Sheet Microscopy

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The aim with this application is to set up a world-leading pole of excellence for live-cell Super-Resolution imaging. The cell is the fundamental unit of all complex life forms and so understanding the biology of the cell and its component parts is a key goal in life science and medicine. Next-generation microscopes are profoundly changing the way cells, sub-cellular structures, and tissues can be studied. More than ever before, our ability to remain a leading research institution in biomedical sciences requires us to stay abreast of new, transformative imaging technologies. To further our understanding of health and diseases requires a deep knowledge of the cell and its constituents. One main path toward this goal is to be able to image the behavior and functional properties of large populations of cells over time. This must be done at high spatial and temporal resolution so that dynamic processes can be discovered and studied. Importantly, imaging of cells and tissues must also be done while preventing photo-toxicity, which can lead to artefacts and even cell death. Advanced optical techniques such as light sheet microscopy, allow for such dynamic studies at low photo-toxicity. Here we request funds to enable us to acquire and set up a novel ultra-fast, exquisitely sensitive, lattice light sheet microscope that will transform our research capabilities in cell and developmental biology. The microscope will be accessible to a wide variety of researchers addressing many outstanding questions relating to embryonic development, cell biology and neurobiology in both normal and disease conditions.To accurately understand and study cellular systems requires imaging at low-illumination minimizing light-induced perturbation of the sample. Photo-toxicity is a main issue in light microscopy, that is know to induce artefacts and cell death. This critical problem is being addressed at UCL with the aim to provide our research-community with the capacity to follow cells at high-resolution and with minimal perturbation. UCL has been instrumental in developing and implementing optical approaches tackling the problem of photo-toxicity. In the recent years, UCL has entered a new and exciting partnership with a small size company, 3i, whose area of expertise is to design and assemble state-of-the-art microscope, including new generating light sheet microscopes which enable live cell imaging with minimum photo-toxicity. Together UCL and 3i are engaged in joint projects that aim at developing new technologies enabling Super-Resolution long-term imaging, through light-sheet microscopy (LLSM). Here we request for support to acquire a LLSM - considered the best performing microscope for simultaneous imaging depth, speed, resolution and specimen viability. This system is uniquely available through 3i and will be transformative for cell and developmental biology at UCL by enabling long-term, Super-Resolution imaging of cells and subcellular structures and compartment. The LLSM will complement another type of light sheet microscope called Dual-View Inverted Selective Plane Illumination Microscope (diSPIM), which will be assembled by 3i at the LMCB as part of our collaborative agreement. This particular combination of instruments will transform the ways UCL researchers are designing and implementing live and tissue imaging.