Integrative Biological Imaging Network (IBIN)

为了了解和对抗人类疾病的起因，我们必须了解构成人体组织和器官的单个细胞的基本结构和功能。例如，为了设计针对癌症的有效疗法，我们首先需要回答关于细胞的生长、分裂和运动是如何被控制的基本问题。罗伯特·胡克在1665年第一个使用显微镜来描述细胞结构，从那时起，显微镜已经成为世界上细胞生物学家最强大的工具之一。光学显微镜自发明以来，其功率当然不断提高，但最引人注目的进步是在最近十年左右出现的。在此期间，物理学家们已经找到了测量细胞中单个蛋白质位置的方法，其精确度比以前认为的要高十倍。这很重要，因为我们现在可以更详细地看到细胞的内部结构和组织。与此同时，物理学家与生物学家一起开发了显微方法，这种方法不仅可以绘制细胞内特定蛋白质的位置图，还可以绘制出一种蛋白质与另一种蛋白质结合的精确位置图。这是一个根本性的进步，因为细胞功能是由特定蛋白质之间的这种相互作用的途径和网络控制的。这些新型显微镜有可能为我们提供一扇了解细胞内部工作原理的窗口，使我们能够看到这些蛋白质网络。然而，目前，最详细的图像只能从化学保存的细胞中获得，而不是从活细胞中获得，每张图像都需要几分钟才能记录下来。这是一个严重的问题，因为控制细胞功能的蛋白质之间的相互作用发生在秒的时间尺度上，并且可能发生在活细胞内的不同地方。这些方法目前也仅限于观察单个细胞中的这些分子，而不是细胞群体。这提供了非常有限的理解细胞如何在组织内沟通，以及这些过程如何在不同的疾病环境中出错。在目前的提案中，生物学家、物理学家、化学家和数学家将作为一个团队共同开发新技术和方法，以成像三维组织中活细胞中发生的事件。通过结合来自不同科学背景的想法，我们将能够开发出解决这些问题的新方法，并在一系列不同类型的技术方面培训科学家，使他们具备进行创新实验的关键技能。我们认为，这些新的发展将释放显微镜的潜力，向我们展示细胞在分子水平上是如何工作的，并为我们分析细胞在正常健康组织和疾病中是如何工作的提供方法。

To understand and combat the causes of human disease, we must understand the basic structure and function of the individual cells that make up the tissues and organs of the human body. For example, to allow the design of effective therapies to target cancer we first need to answer fundamental questions about how the growth, division and movement of cells are controlled. Robert Hooke was the first to use microscopes to describe cell structure in 1665, and since then microscopy has become one of the most powerful tools for cell biologists across the world. The power of light microscopes has of course continued to increase since their invention but, remarkably, the most dramatic improvement has come in the last ten years or so. In that period physicists have worked out how to measure the location of a single protein in a cell with a precision about ten times better that was previously thought possible. This is important because we can now see the internal structure and organisation of cells in much more detail. In parallel, physicists working together with biologists developed microscopical methods that, instead of just producing a map of the locations of one particular protein inside a cell, can produce a map of precisely where one protein is bound to another. This is a fundamental advance, because cell function is controlled by pathways and networks of such interactions between specific proteins. Potentially these new microscopes provide a window into the internal workings of a cell that allow us to see these protein networks. However, at the moment, the most detailed images can only be obtained from chemically preserved rather than living cells, and each image takes minutes to record. This is a serious problem, because the interactions between proteins that control cell function take place on the time scale of seconds and can occur at different places inside living cells. These methods are also currently restricted to looking at these molecules in single cells, not populations of cells. This provides very limited understanding of how cells communicate within tissues, and how these processes go wrong in different disease settings. In the present proposal, biologists, physicists, chemists and mathematicians will work together as a team to develop new technology and approaches to image events that occur in live cells within 3-dimensional tissues. By combining ideas from different scientific backgrounds, we will be able to develop novel ways to tackle these problems and train scientists in a range of different types of techniques so they are equipped with key skills to perform innovative new experiments. We think that these new developments will unlock the potential of microscopy to show us how cells work at the molecular level and provide ways for us to analyse how cells work in normal healthy tissues as well as in diseases.