Advanced live imaging for the Eastern ARC with dual inverted light-sheets and AI-led analysis

Microscopy has turned into an incredibly exciting area of research over the last two decades, with two recent Nobel Prizes and many new technological developments. Scientists can now observe cells moving around, digesting, interacting, multiplying and assembling at high resolution and over long periods. But cells are easily damaged if intense light is focussed on them. So when observing cells with a microscope, it is important to minimise such photodamage by lowering the light intensity. However, lower levels of light result in poorer images in the microscope and less useful information, so there is a clear dilemma between high light (good image, but cells damaged) and low light (cells healthy but image worse). Lightsheet microscopy, a relatively new technique, can solve this issue by providing good images at low light intensity: Delicate cells, tissues and whole organisms are scanned with a 'sheet' or plane of light and can be observed over days, producing breathtaking movies. Together with collaborators across the Eastern Arc, which comprise the universities of Essex, Kent and East Anglia, we want to use a high-end light-sheet microscope in combination with cutting-edge software to address new and exciting biological questions. This will allow many research groups in the South East and East of England to use light-sheet microscopy for their investigations. By establishing a nation-wide light-sheet user group to share new ways to use light-sheet microscopes. By making this technology more accessible to users, imaging with light sheets is poised to give us new insights into biological systems in ways we may not have thought possible.

Within the Eastern Academic Research Consortium (Eastern Arc), comprising the universities of Essex, Kent and East Anglia, we want to use a unique light-sheet microscope, the Marianas LightSheet (MLS) by 3i, together with best-in-class image processing and analysis software Aivia. The MLS is a powerful imaging approach that enables high-speed, high-resolution imaging of live samples at low-to-no phototoxicity, with optical sectioning and large fields of view. It will be applied to functional and developmental imaging in a wide range of model systems. Powerful bioimaging technologies need to be available at a local level. This is particularly true for affordable technologies that have the potential to be widespread and are slowly finding their way into more general, non-specialist research settings, such as light-sheet fluorescence microscopy. In the South East and East, coverage of LSFM is sparse. This is a significant regional gap of LSFM expertise and instrument availability. An instrument at the University of Essex, where the main applicant is a highly research- and training-active member of the light-sheet community, would be an important first step towards filling this gap. We have the expertise and facilities to conduct the original research projects detailed in this application, establishing innovative ways to image important biological model systems that lie within the BBSRC's strategic priorities.