The Dynamic Embryo Imaging Platform

了解细胞及其组成部分的生物学一直是生命科学和医学的关键目标。显微镜的进步正在深刻地改变细胞、亚细胞结构和组织的研究方式。对于像伦敦大学学院这样的研究密集型机构来说，要保持生物医学科学领域的竞争领先地位，采用变革性的成像技术是至关重要的。要加深我们对健康和疾病的了解，需要对细胞、其成分及其从生命早期阶段的发育有深入的了解。如何在没有光毒性或光漂白的情况下，用具有合适灵敏度的探测器捕捉低信号强度，以高空间和时间分辨率对完整的、大规模的活体生物进行成像仍然是一个关键挑战。作为生物科学/生物医学发现的关键贡献者，伦敦大学学院的国际声誉之所以成功，部分原因是它通过投资资本和资源，始终致力于成为新的、变革性技术的早期采用者。实现这一目标的一个主要途径是描绘细胞随时间推移的行为和功能特性。这必须使用能够以足够精细的细节和非常高的速度捕获图像的设备来完成，以便能够发现和研究迄今未知的动态过程。LightSheet成像技术特别适合于研究胚胎发育过程中的关键事件，特别是快速细胞事件，部分原因是它能够扫描整个活组织，并构建高速发展的生物体的三维图像。先进的光学技术，如光片显微镜，使这种动态研究成为可能，同时也允许研究人员操纵细胞功能。将这项技术添加到UCL核心成像学院将使研究人员能够获得以下能力：a)快速特征跟踪，以研究细胞内过程、细胞迁移和胚胎发育。b)解决与其他成像技术相关的光学散射问题，并允许深入厚样本进行成像。c)快速捕获细胞信号事件，如钙成像，深入整个胚胎区域，如CNSD)，以检测活组织中细胞内和细胞之间的分子相互作用事件，如斑马鱼胚胎。因此，这项提议的主要共同申请者是，伦敦大学学院的研究小组专注于胚胎发育的各个方面，试图阐明支撑生物发育和健康疾病的基本过程和关键事件/因素。他们代表了伦敦大学学院的一些主要研究人物，他们的研究得到了BBSRC、MRC、CRUK和Wellcome Trust赠款的广泛支持。此外，显微镜将可用于大量不同的研究项目，解决与胚胎发育、细胞生物学和神经生物学有关的许多悬而未决的问题。申请的资金将使我们能够获得一台领先的LightSheet显微镜，这将显著增强我们的研究能力，并导致新的科学发现。

Understanding the biology of the cell and its component parts has always been the key goal in life science and medicine. Advances in microscopy are profoundly changing the way cells, sub-cellular structures and tissues can be studied. For a research intensive institution, such as UCL, to remain a competitive leader in biomedical sciences, it is essential to adopt transformative imaging technologies. Furthering our understanding of health and diseases requires a deep knowledge of the cell, its constituents and their development from very early stages of life. How to image intact, large-scale, live organisms at high spatial and temporal resolution with multiple fluorophores/reporters without phototoxcity or photobleaching with detectors of suitable sensitivity to capture low signal intensity remains a key challenge. UCL's international reputation as a key contributor in bioscience/biomedical discoveries has, in part, been successful because of it's sustained commitment to be an early adopter of new, transformative technologies, by investment of capital and resources. One main path toward this goal is to image the behavior and functional properties of cells over time. This must be done with equipment that is capable of capturing images with sufficient fine detail and at very high speed so that, hitherto, unknown dynamic processes can be discovered and studied. Lightsheet imaging technology is particularly suited to the study of key events during embryogenesis, especially fast cellular events, in part because of its ability to scan through living tissue and construct three-dimensional images of developing organisms at high speed. Advanced optical techniques, such as lightsheet microscopy allow for such dynamic studies while also allowing researchers to manipulate cellular functions. The addition of this technology to UCL core Imaging faculty will give researches access to capabilities such as:a) Rapid feature tracking to study intracellular process, cell migration and embryo development.b) Address optical scattering problems that are associated with other imaging techniques and allow imaging deep into thick samples.c) Rapid image capture of cell signalling events such as calcium imaging, deep into whole embryos regions such as the CNSd) To detect molecular interaction events within and between cells in live tissues and whole organisms such as zebra fish embryos.The main co-applicants on this proposal are, therefore, research groups at UCL whose focus is on aspects of embryo development trying to elucidate the fundamental processes and key events/factors that underlie organismal development and in health disease. They represent some of the major research figures at UCL, whose research is extensively supported through BBSRC, MRC, CRUK and Wellcome Trust grants. In addition, the microscope will be accessible to a large number of diverse research projects addressing many outstanding questions relating to embryonic development, cell biology and neurobiology. The requested funds will enable us to obtain a one of the leading Lightsheet microscope that will significantly enhance our research capabilities and lead to new scientific discoveries.