Optical Functional Imaging For Metabolic Cell Model Engineering and Profiling

From the earliest invention of the camera, humans have been seeking to observe processes that are too fast or too complicated for the human eye and brain to determine. Our understanding of cellular function continues to evolve as we observe complex dynamic processes played out under a microscope, captured by a camera at high speed and slowly revealing its hidden intricacy. As biologists ask every more complex questions, so we must develop more sophisticated tools to rationalise the complex data that we observe. Our current understanding of protein interaction in cells is informed, principally, using microscopical tools to delineate localisation and compartmentalisation of signalling events within cellular organelles such as mitochondria. We will develop advanced microscopical tools to enable the study of metabolism using fluorescent biosensors to elucidate fundamental processes occurring throughout cells and tissues using either light-producing molecules the cells naturally produce or novel biosensors. This project transcends traditional disciplinary boundaries, so we will focus our optical and electronic engineering solutions for application to multiple complementary fields such as neuroscience and cancer, demonstrating similarity in research methods but striking differences in research questions. We will measure small numbers of fluorescent molecules; for the nanoscale, enabling us to probe the dynamic responses of cellular components such as the mitochondrion (the cell’s metabolic power plant) or the connections between cells (such as the synapses between neurons int the brain); for the cellular scale, to observe cell responses to cancer treatments, correlating immediate high-speed metabolic responses; and for the mesoscale, to observe contrasting metabolic profiles in cell types (cancer and normal tissues or neurons and glia within bioengineered organoids). With these tools we will deepen our understanding of how metabolism and homeostatic signalling at the nanoscale, propagates across distances within single cells and across tissues. This new model of molecular communications will allow exquisite acquisition of live quantitative data directly connected to cellular activity, through simultaneous imaging of large multicellular volumes.