Let there be - Sheets of - Light.

Bioimaging is one of the fastest evolving technologies. Just a decade ago visualising and measuring developmental and disease processes in molecular detail in living cells, in three dimensions, was unimaginable. While standard confocal and wide-field fluorescent microscopes can image in 2D, bioimaging in the third dimension in live samples over time is a challenge. High laser light doses damage biological processes and kill cells and organisms. Slow image acquisition and distortions in the Z (or axial) plane limit 3D studies. A new generation of microscope which use sheets of light for 3D live imaging has been pioneered to address these limitations. We are applying for the most recent version of this technology a Lattice Light Sheet Microscope. This new instrument uses structured sheets of light to speed image acquisition, enabling fast acquisition of 3D images at sub-micron resolution with minimal distortion. Zeiss launched the Lattice Light Sheet 7 (LLSM) in 2022, developed in consultation with core facilities and end users. It is straight-forwards to use, does not require complicated sample preparation, is stable over several days and able to image a wide range of samples using micron thin sheets of light. We need sub-micron resolution for our science. Previous iterations of the technology couldn't show us the detail needed due to: lack of resolution, sample preparation requirements which were incompatible with our biomedical research applications, issues with the illumination field or complexity of operation for our facility users. The equipment will be housed in the Advanced Imaging Resource (AIR), Institute of Genetics and Cancer (IGC), University of Edinburgh (UoE). AIR comprises equipment and six expert technical staff have particular expertise in very high-resolution imaging of fixed and live samples. Coupled with methods developed from our molecular and developmental biologists, this will ensure that the LLSM is used in a wide array of biomedical applications. The IGC has specialist expertise in interrogating how small changes to DNA in the genome impact development, cancer and disease. We are delighted to have several early career researchers onboard with this application. The LLSM will be used to tackle biomedical questions including; How gene regulation from the non-coding genome controls development of the face and eye, How variations in the human genome contribute to poor cancer, and other disease, prognosis and outcomes How liver bile ducts form and are repaired How the molecular construction of cilia contributes to disease We are committed to open science. To ensure the technology is available to a wide audience we will incorporate the LLSM into ESRIC (The Edinburgh Super-Resolution Interdisciplinary Consortium), a national centre of excellence for super-resolution microscopy. ESRIC is a collaboration between the IGC and Heriot Watt University, it offers an open access core facilities across both sites, with some equipment being housed within AIR - 'a facility in a facility'. ESRIC is one of seven sites which comprise the UK node of EuroBioimaging, providing national infrastructure for open-access state-of-the-art bioimaging resources. We offer specialist training courses to pass on our expertise. To summarise, the LLSM will enable a significant step forward in research capabilities, at a large MRC Unit, within the IGC, regionally within Edinburgh. It will also benefit research both nationally / internationally through the EuroBioimaging UKnode.