CAREER: New Reporters for Temporally-Gated Integration of Neuronal Activity

With the support of the Chemistry of Life Processes Program in the Chemistry Division, Wenjing Wang of the University of Michigan will develop new molecular tools to study brain signaling-specific neuronal populations. Functional neuronal populations, activated during specific behaviors, underlie our cognitive functions and behaviors. They are usually sparsely scattered among other seemingly identical neurons, and, therefore, are challenging to access for further study. Currently, there is still a need for reporters to label these functional neurons with readout within minutes after detecting the neuronal activity. The proposed project to address this need has broad potential impact on molecular biology and neuroscience. Additionally, the proposed research will provide graduate and undergraduate students training opportunities to acquire knowledge of and advanced skills in molecular biology and protein engineering techniques. Frontline research results generated from this project will be incorporated into graduate level course materials and, in collaboration with the Museum of Natural History at the University of Michigan, in science communication with the public. This project seeks to develop a new class of reporters for labeling neuronal populations activated during specific behaviors. The reporters’ ability to answer quickly relies on the fast activation of an enzyme by chemical changes caused by neuronal activity. Directed evolution and rational protein design methods will be applied to the development and optimization of the reporters in cell cultures first and then in animal models. The optimized methods would allow the study of neuronal activity in animal models by immediate labeling of neurons upon detection of the signaling events. The new reporters have the potential to facilitate the interrogation of neuronal activity and circuits that underlie behaviors. The proposed methods, if successful, are expected to have broad scientific impact as they could, in principle, be applied to the study of a wide range of biological processes that involve protein-protein interactions. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.