An Airyscan 2 confocal laser scanning microscope for the Wolfson Light Microscopy Facility

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Human diseases arise because of defects in fundamental biological processes. These processes depend on interactions between molecules within cells, between cells within tissues and tissues in the whole organism. In order to understand and identify effective therapeutics we need to understand the dynamic nature of biological processes and observing such processes in living cells is fundamental to this understanding. Visualisation both validates other experimental approaches but, importantly, often allows us to formulate new hypotheses. At the University of Sheffield biomedical researchers are exploring the fundamental way in which molecules, cells and tissues behave in order to understand what goes wrong in diseases such as cancer, infection, inflammation, deafness and neurodegeneration. In order to observe biological processes we often attach fluorescent labels to components of interest and follow their behaviour using fluorescence microscopes. The time-scale of biological processes is highly variable: some processes happen very quickly, meaning that images need to be acquired speedily while others occur over a much longer time-scale of minutes to hours. There are a number of challenges associated with capturing fluorescence images because the exposure of cells to light can cause phototoxicity which damages cells and causes aberrant behaviour. Additionally, some fluorescent labels can be quite dim which makes the fluorescent signal difficult to detect. The aim of this proposal is to obtain funding for the latest Airyscan 2 confocal laser scanning microscope (CLSM). This microscope will not only replace the functionality of two existing but very old fluorescent microscopes which are difficult to maintain, but will also improve our ability to observe very small structures within cells and/or to observe highly dynamic processes which occur very rapidly. The advanced performance of the Airyscan 2 CLSM will overcome current limitations in understanding fundamental mechanisms that underpin disease.