A Chemical Imaging Platform for Discovery Biosciences (CIP-DB).

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Understanding the biology of cells, their component molecules and behaviors and characteristics when aggregated into tissues has always been a key goal in life science and medicine. Advances in microscopy are profoundly changing the way cells, sub-cellular structures, molecules and tissues can be studied. For a research intensive institution, such as UCL, to remain a competitive leader in biomedical sciences, it is essential to adopt transformative imaging technologies when their power is recognized, the technology is affordable, well understood and established as viable for transformative bioscience work. Furthering our understanding of health and diseases requires a deep knowledge of the cell, its constituents and their development from very early stages of life. How to image intact, large-scale, live or preserved postmortem cells, tissues and organisms at high spatial and spectroscopic resolution with and sensitivity remains a key challenge.UCL's international reputation as a key contributor in bioscience/biomedical discoveries has, in part, been successful because of it's sustained commitment to be an early adopter of new, transformative technologies. One new and powerful pathway toward this goal is to image directly (without the use of reporter probe molecules) the chemical and biochemical properties of cells and tissues over time. This must be done with equipment that is capable of capturing at high speed images with sufficient fine spatial detail and at very high chemical resolution so that hitherto, unknown processes can be discovered and studied. Raman imaging technology is particularly suited to the study of key distibutions and properties of biomolecules during embryogenesis, tissue differentiation, changes in phenotype during health and disease and performance of their biochemical function. CIP-DB will add a new dimension of support to cutting edge research in life and biomedical sciences. The Raman microscope is a unique system that enables acquisition of highly detailed, qualitative and quantitative information on the chemical composition of a tissue or cellular sample pixel-by-pixel. From this data images displaying the distribution of chemical species much like a multi-idimensional virtual staining, but without the introduction of probes, dyes, antibodies or genetically encoded markers, can be constructed. These images provide rich biochemical and molecular biological information and their spatial distribution. This characterization of biological samples is essentially orthogonal to that collected through other light microscopic techniques like the fluorescence imaging used almost universally and exclusively in modern cellular biosciences. Furthermore confocality and near infrared illumination will allow deep probing of samples and 3D chemical image reconstruction. Contour tracking technology will allow application of the technique to non-flat, rough or complex surfaces. This will allow unprocessed tissue samples to be analysed as well as samples where the thickness is changing over the duration of the experiment through growth, swelling or other changes.The main co-applicants on this proposal are, therefore, research groups at UCL and colleagues in nearby research institutes whose focus is on aspects of molecular cell and developmental biology and biochemistry trying to elucidate the fundamental processes and key events/factors that underlie organismal development in both health and disease. In addition, the microscope will be accessible to a large number of diverse research projects addressing many outstanding questions in fundamental biosciences. The requested funds will enable us to obtain a one of the leading Raman microscope that will significantly enhance our research capabilities and lead to new scientific discoveries.