A new microscope at the University of Leicester will use ultrathin sheets of light and virtual reality to watch living cells, proteins, and tissues interact in real time, deep inside three-dimensional biological samples. Standard microscopes struggle to see clearly into thick, living tissue without damaging it with too much light. This lattice light-sheet microscope solves that problem by illuminating only a single thin slice of the sample at a time, using specially shaped beams that are far thinner than conventional light sheets. This boosts resolution while minimising light exposure, so cells stay alive and active during imaging. Adding a virtual reality toolkit lets researchers navigate through the resulting 3D data, revealing interactions between molecules and cells that were previously hidden deep inside the sample. If successful, this facility will accelerate fundamental discoveries in how organisms develop, regenerate, fight infection, or succumb to disease. It will also help replace, refine, or reduce the use of animals in research by enabling detailed live-cell imaging instead. The system is primarily a tool for fundamental biology—understanding the multiscale machinery of life—rather than a device with immediate clinical or commercial applications. Past investments in similar advanced microscopes have led to unexpected insights into cell division, cancer progression, and immune responses.
View original technical description
Multiscale biological processes mediate human health and the diseases we suffer. To develop an integrated understanding of these processes in a manner that allow us to exploit them to our advantage requires that we 'see' how biological agents (organs, tissues, cells, proteins) interact with each other and their environment. Live microscopy of biological systems allows us to visualise these agents in action. To visualise the agents of interest, we 'label' them with a fluorescent molecule, which can be detected by fluorescence microscopes. The rationale is that when these agents are alive or inside a living system, these fluorescent labels can help show the real-time activity of the agents they are bound to, i.e. we can see agents in action: an approach referred to as live cell imaging. We can thus monitor the movements of proteins or their interactions and visualise which cells organise together or move apart during disease. Light-sheet microscopes are specialised fluorescence microscopes that visualise these labels by illuminating only a thin slice of a sample with sheets of light, enabling 3D optical sectioning. In Lattice Light-sheet microscopy, advanced beams are used to create lattice-shaped light sheets, which are significantly thinner than standard light sheets. This significantly enhances resolution and minimises samples' exposure to light. By combining selective labelling with advanced methods to distinguish two or more molecules with different labels, we can even visualise and investigate the intracellular machinery non-destructively, revealing interactions between multiple molecular mechanisms within living cells. Further, combining this setup with Virtual Reality toolkits that enable advanced visualisation and analyses open up previously inaccessible regions of interest deep within the sample. This allows us to study these processes in more detail than previously possible. The University of Leicester (UoL) is a recognised leader in conducting world-leading biomedical research and part of the vibrant life science imaging community in the Midlands. UoL researchers are devoting significant activity to understanding the multiscale biology of development, regeneration, diseases, and infection. However, lack of a suitable microscope and facility is impeding critical research, discovery, and innovation. We aim to overcome this by installing the Lattice Light-Sheet 7 microscope that will enable improved depth penetration for live cell imaging combined with high-throughput, high-content imaging. This system will be fitted with virtual reality toolkit to undertake sophisticated analyses that will drive our science, training, and public outreach. We will always develop a facility to house this system. Ultimately, with Zeiss, this facility and system will help us develop a centre of excellence in bioimaging that will serve the Midlands and beyond. This will significantly enhance our capability to contribute to BBSRC's strategic priorities, including 1) understanding the multiscale biology of development, regeneration, and disease; 2) understanding host-microbe interactions; 3) combatting infections; 4) developing techniques to replace/refine/reduce use of animals; and 5) engineering biology. This setup will also turbocharge the university's efforts to advance our interdisciplinary biomedical research, teaching, and training. Our proximity to industrial and academic partners in Leicester and the Midlands, especially our interactions with them contextualised by the Centre of Excellence, will result in an unprecedented pooling of expertise that will be transformative for development and commercialisation of transformative technologies that will ultimately secure better health, ageing and wellbeing for everyone.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know