Development and application of automated multiwell plate fluorescence microscopy

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This project involves the development of a modular open source automated fluorescence microscope platform based on Micromanager and incorporating an optical autofocus module. This will enable automated fluorescence lifetime imaging (FLIM) for assays of protein interactions and changes in cell metabolic processes. A multibeam multiphoton excitation scheme will be explored for optical sectioning and label-free contrast based on autofluorescence. Automated super-resolved imaging with single molecule localisation microscopy techniques will also be implemented. This platform will be developed with open source software and low-cost components where appropriate to widen access to these advanced microscopy techniques. Applications of these imaging modalities to medical research will be explored including to heterogeneity in the host-pathogen of macrophages for COPD, to studies of cellular metabolic changes associated with the differentiation of embryonic stem cells and with cancer and to the temporal and spatial regulation of activation-induced deoxycytidine deaminase (AID) in the cell nucleus.