4D imaging of the dynamic molecular, cellular and tissue organization in living systems

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Microscopy is an essential tool for revealing how living systems are composed and how they function. Recent advances have enabled researchers to see deep inside tissues and at high resolution within cells. A limiting factor, however, has been that the powerful illumination required causes damage to living samples, which reduces how long they can be observed. A new technology, called the inverted lattice lightsheet microscope, overcomes this problem and allows for the first time gentle long-term imaging of live cells and tissues. This new microscope is a game changer in our ability to observe living cells, the basic units of life, and examine their full range of behaviours in health and disease. In addition to low phototoxicity and high resolution into 3D multicellular structures, the Zeiss lattice lightsheet 7 microscope has a unique inverted design, which is ideal for imaging cell and tissue cultures. This configuration also allows multiple samples to be tracked in parallel in multiwell plates, which controls for sample bias and generates statistically powerful datasets from a single long-term imaging experiment. The multiwell option can greatly increase experimental throughput and enable small scale chemical and genetic screens.This proposal is to purchase and install an inverted lattice lightsheet microscope in the University of Exeter Bioimaging Center. The microscope will be available to life sciences researchers across Exeter and in our partner Universities in the SouthWest, Bath, Bristol and Cardiff. Using this instrument, we will be able to see in great detail how cells change identity and build tissues during development, how different cell types communicate and cooperate to provide complex functions, and how multicellular tissues are disrupted by infection and disease.The Exeter Bioimaging Centre has a range of high-resolution microscopes but lacks an instrument capable of tracking cell behaviour in multicellular structures or small organisms. Our team of applicants brings together world-leading senior researchers, microscope technology specialists, and highly talented junior independent investigators. The cutting-edge research that will benefit from the microscope includes studies on fungi, plants, marine invertebrates, zebrafish and human. Example projects span investigations into molecular signalling, stem cell fate, embryo formation, organogenesis, drug safety, cell-cell communication, plant pathogen interactions, and the biophysics of ciliary motion. The high volume of quantitative data obtained with the new microscope will foster interdisciplinary collaborations between biologists and mathematicians and physicists aimed at elucidating the rules of life using rich, complex and exciting long-term imaging information.