Zeiss Lightsheet 7 Microscope: Transforming Imaging for Bioscience Discoveries

Microscopes allow us to see a world that is not visible with the naked eye. We can see in astonishing detail how the machinery of individual cells work. This includes how cells respond to nutrients and store energy, how brain cells process information controlling behaviour or change during ageing and how our immune system fights off attack from infections. Our current microscopy equipment allows us to see inside cells in very high resolution by focussing only on one "slice" of information at a particular depth. Information above and below the "slice", which would make the image blurred and hard to understand, is ignored. However, this only works for very thin slices, perhaps one or a few cells thick. Moreover, the illumination these systems use can cause damage to cells and tissues. This limits how long they can be imaged, particularly when using live cells. Light sheet microscopes revolutionise conventional microscopy. Using special chemical methods, we can make samples more transparent, and by shining light, we can visualise whole organisms or organs in three dimensions without damaging the tissue. In addition, light sheet microscopy takes a fraction of the time it would take to image different depths in the cell with our existing microscopes. As an example, we can use this method to image a whole rodent brain, visualising an astonishing variety of nerve cells that connect throughout the brain in exquisite detail. This will let us see new connections that hold the key to understanding how we collect and process information from our environment, how this may influence things such as obesity, diabetes, mood or addiction or how to promote healthy ageing in the brain and prevent conditions such as dementia. This new equipment would transform the range of exciting work we can do at the University of Aberdeen. We already have funding for a range of projects from the BBSRC that could be taken to a new level by using light sheet microscopy. This would drive forward our world leading research in areas such as nutrition and metabolic health, healthy ageing and infection and parasitology. It would also open exciting new opportunities for ground-breaking research to understand the fundamental rules of life. We have a dedicated University supported facility for microscopy at the University of Aberdeen with highly skilled staff who train researchers and provide expert advice at all stages of our projects. The light sheet microscope would be part of this world-class facility keeping us at the cutting edge of bioscience imaging. Importantly, there are no similar facilities or equipment in the north of Scotland and the most exciting applications involve live imaging which requires on site facilities. Simply put, the combination of this cutting-edge equipment with the world-class expertise in key priority areas for BBSRC funding mean that the award of this funding would genuinely transform the capacity for even greater high impact, exciting research in nutrition, healthy ageing, dementia, infection and much more at the University of Aberdeen and the north of Scotland more widely.

We request funds for a Zeiss Lightsheet 7 to transform a diverse range of projects that are central to BBSRC's priority areas and strategic plan at the University of Aberdeen. There is no equivalent equipment anywhere in the north of Scotland. Hence, this would provide a hub of cutting-edge imaging for academic and industry researchers in the wider region of Scotland urgently in need of this capability. The light sheet microscope will be housed in the University's Microscopy Core Facility and will be maintained by our expert facility staff who have a strong track record of providing training, advice and imaging services in state-of-the-art microscopy to both the University and external users.
Conventional confocal microscopes enable high resolution images of fluorescently labelled samples through elimination of out of focus light. However, photobleaching and phototoxicity are major limitations, especially for live cell imaging, as the entire depth of the sample is exposed to light. Also, the depth of imaging is restricted to around 100 um. In contrast, light sheet microscopy enables fast, non-destructive imaging of live specimens or large whole organs and tissues at high resolution. Light sheet microscopes illuminate a single section of the sample at a time with a thin sheet of laser light. The signal is then collected only from the in-focus plane, minimising phototoxicity. Large samples, up to 2 cm, such as entire embryos, organoid cultures, zebrafish, nematodes and adult rodent organs, can be imaged at unparalleled subcellular resolution. This provides exquisite detail and information impossible to gain using conventional sectioning and histological approaches. Hence, on site-access to the Lightsheet 7 microscope will provide a major advance in our capacity to generate high impact, exciting novel discoveries in the biosciences by multiple research groups across the University and the north of Scotland.