Activity biosensors reveal signaling dynamics in living systems

We developed several general strategies for engineering fluorescent biosensors to track the activities of second messengers, kinases and phosphatases. Quantitative measurement from live-cell fluorescence imaging can be combined with mechanistic computational modeling for systems analyses of signaling networks. We further demonstrated the first high-throughput compound screen based on reading dynamic kinase activities in living cells and are realizing live-animal imaging of dynamic signaling activities in collaboration with the Rick Huganir laboratory (JHU), extending the application of these fluorescent biosensors to chemical probe identification, drug discovery and mechanistic studies in en vivo contexts.