Multimodal coherent Raman and two-photon fluorescence imaging as a discovery tool in bioscience

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Bioimaging is a fundamental technology underpinning bioscience and has been instrumental in unravelling the complexities of biological systems that control tissue development, differentiation and that drive disease processes. Our approach has been to combine label-free coherent Raman imaging modalities, which generate image contrast using the Raman active vibrational frequency of a given chemical, with two-photon fluorescence imaging modalities to provide insight into both subcellular and tissue organisation. Recent advances in biorthogonal chemistry which allows Raman tagging and subsequent visualisation of small drug molecules, drug delivery vehicles and cellular constituents has extended the benefit of this technology to a much wider scientific base.Several advances in instrument design have been made since we set up our current multimodal imaging platform in 2011 which means that we can significantly enhance and extend the imaging capabilities by increasing the stability, sensitivity, accuracy and speed of our measurements, while also enabling imaging of far-red fluorophores which are becoming increasingly popular in the design of in vivo probes due to the enhanced penetration of higher wavelengths into tissue. The new set-up will provide a unique platform to carry out intravital imaging in live animals, including mice and zebrafish, providing unrivalled insight into spatial and temporal control of fundamental biological processes. In addition, access to the expertise and knowledge of the consortium of researchers that have put together this proposal (who have an excellent track record of publications and securing financial support including from the BBSRC) will drive success and ensure maximal impact of the research undertaken. This will support scientific advances and enable technological innovation that will impact all areas of the biological sciences.The aim of this proposal is to provide a state-of-the-art multimodal imaging platform available to scientific communities across the UoE, other academic institutions throughout the UK, and our partners in industry. The proposal brings together a multidisciplinary consortium of researchers (chemists, biologists, engineers) with expertise in bioimaging with a broad range of diverse research goals. The new platform will therefore underpin scientific research in several key strategic BBSRC priorities for the next decade: combatting microbial resistance; 3Rs in research using animals; sustainably enhancing agricultural production; systems approaches to the biosciences; technology development for the biosciences; synthetic biology.