Engineering fluorescent biosensors to spy on cell signaling and metabolism

The ever-broadening selection of high performance fluorescent protein (FP)-based biosensors is revolutionizing our ability to spy on the otherwise invisible world of intracellular signalling and metabolism. In this seminar I will describe our most recent efforts to use protein engineering to make a new generation of genetically encoded biosensors, and chemigenetic biosensors augmented with synthetic molecules, with improved properties and an expanded range of potential applications. Key to this effort is our reliance on the use of directed protein evolution to iteratively and reliably improve the properties of biosensors. These biosensors include ones for inorganic ions such as Ca2+, K+, and Na+and metabolites such as lactate, pyruvate, and citrate. By creating biosensors with different colors and specificities, we are opening up new opportunities for researchers to use multiplexed imaging to investigate the spatiotemporal interplay of neural activity and neural metabolism in model organisms.