Molecular probes that allow in vivo imaging of neural signaling events are important for investigating the basis of brain activity and neuron disorders. Taking advantage of the malleable nature of the substrate binding pocket of P450 BM3 and the power of directed evolution, we successfully developed P450-based magnetic resonance imaging (MRI) contrast agents for in vivo detection of neurotransmitters including dopamine and serotonin. These genetically-encodable biosensors potentially allow us to noninvasively visualize neural activity in living animals.
We will continue to engineer P450-based sensors with high specificity and sensitivity for molecules of interest, using powerful new capabilities for incorporating non-natural hemes and non-natural amino acids. We are also branching out into new protein engineering applications in neuroscience.