Light Sheet Microscopy for Developmental Biology

克里克是医学研究理事会、英国癌症研究中心、威康信托基金会和三所领先大学的合作伙伴关系：伦敦大学学院（伦敦）、伦敦帝国理工学院（伦敦）和伦敦国王学院（伦敦）。克里克立志成为世界领先的医学研究机构之一。克里克通过集中的设施和功能实现了运营和研究效率以及规模经济，称为科学运营，为克里克的所有研究人员提供了先进的设备，研究动物和实验室功能，如光学显微镜。光学显微镜是一种基础研究工具，具有强大的仪器可执行不同的功能。需要不同的仪器，因为光学显微镜的基本组件的不同布置-光源，透镜系统，样品和检测器-根据其布置具有其应用的优点和缺点。共聚焦显微镜可用于研究培养物中荧光标记细胞的动力学，然而该方法不太适合研究较厚的组织样品。其结果是一个特定的细胞结构的图像，而不知道细胞在器官中的位置，有点像不能看到树木的木材。相比之下，本授权申请的主题光片显微术使用光源和透镜布置，其能够从近平行光（即光片）显影图像。这允许可视化样品深处的细胞和亚细胞结构，例如组织和发育中的斑马鱼胚胎。这一特性使得光片显微镜特别适合研究细胞在正常生长（如胚胎发育）或异常生长（如癌症发展）期间如何生长、移动和组织。通过了解细胞如何生长，移动和组织，我们希望能够确定问题出现的地方并研究如何解决问题，最终导致新的医学方法来支持人类生育，治疗癌症或其他由异常细胞功能引起的疾病。

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.