Light Sheet Microscopy for Developmental Biology

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The Crick is a partnership between the Medical Research Council, Cancer Research UK, the Wellcome Trust and three leading universities: UCL (University College London), Imperial College London and King's College London. The Crick aspires to be one of the world's leading medical research institutes. The Crick achieves operational and research efficiencies and economies-of-scale through centralised facilities and functions, known as Science Operations, that provide all researchers at the Crick, irrespective of affiliation, with access to cutting-edge equipment, animals for research and laboratory enabling functions such as light microscopy.Light microscopy is a fundamental research tool with powerful instruments available to perform different functions. Different instruments are required because different arrangements of the basic components of a light microscope - a light source, a lens system, a sample and a detector - have strengths and weaknesses for their application depending on their arrangement. Confocal microscopy can be used to study the dynamics of fluorescently labelled cells in culture, however the method is poorly suited for the study of thicker tissue samples. The result is an image of specific cell structures without knowing where the cells sits in an organ, a bit like not being able to see the wood for the trees. In contrast, Light sheet microscopy, the subject of this grant application, uses a light source and lens arrangement that is able to develop an image from near-parallel light i.e. a light sheet. This allows visualisation of cells and sub-cellular structure deep within samples such as tissue and developing zebrafish embroys. This attribute makes light sheet microscopy particularly powerful for studying how cells grow, move and organise during normal growth e.g. as embryos develop, or abnormal growth e.g. as cancer develops. By understanding how cells grow, move and organise we expect to able to identify where problems arise and investigate how to solve problems, ultimately leading to new medical approaches to support human fertility, treat cancer or other diseases that are caused by abnormal cell functions.