Integrative Biological Imaging Network (IBIN)

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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.