Optical Functional Imaging For Metabolic Cell Model Engineering and Profiling

Spatial-temporal regulation of cell-signalling, and metabolism is crucial to maintain function within cells and tissues.

In this proposal we will develop advanced microscopical tools which will enable the study of metabolism using fluorescent biosensors to elucidate fundamental processes occurring across diverse scales of time and space.

The development of advanced microscopical tools transcends traditional field boundaries, so we will develop two complementary fields (neuroscience and cancer), demonstrating similarity in research methods but striking differences in their research questions.

We will develop imaging methods; for the nanoscale, enabling us to probe the spatio- temporal response of mitochondrion or at the cellular interface; for the cellular scale, to observe cell responses to perturbation, correlating immediate high-speed metabolic response; and for the mesoscale, to observe contrasting metabolic profiles in cell types within tissue and engineered constructs in correlation with complementary technologies.

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 organoids.

This new model of molecular communications will allow exquisite acquisition of live quantitative data on calcium, ATP metabolism and any other fast-changing dynamic processes directly connected to cellular activity, through simultaneous imaging of large multicellular volumes.