To truly understand how our brains regulate our behaviors, neuroscientists need genetic and molecular access to clear snapshots not just of the entire brain, but of specific neurons firing during a behavior.
“The problem is, there really is no perfect tool that allows us to interrogate those specific neurons that are firing at a given time,” says Wenjing Wang, Ph.D., who just began a new faculty position at the University of Michigan.
It’s a problem that Wang will tackle with her research program at the U-M Life Sciences Institute.
Wang is using her extensive protein engineering expertise to create tools that will use different light colors to ‘tag’ neurons firing in mice during a given activity. These tools help advance neuroscience research by allowing investigators to identify neurons that are active during a defined window of time. For example, researchers could label neurons activated by fear with one color, and label neurons activated by the reduction of fear using another color.
“Then we can actually study how the neurons differ at the molecular level and determine how the neuronal projections to different regions of the brain result in different valence,” explains Wang, who holds a joint appointment at the LSI, where her lab is located, and in the Department of Chemistry at the U-M College of Literature, Science, and the Arts.
These new tools will also have utility beyond neuroscience, enabling researchers to investigate the detailed ways in which other cell types, such as secretory endocrine cells, regulate activities like metabolism — and how disruptions in those pathways lead to disease.
The work builds upon a tool that Wang developed while working in the lab of Alice Ting, Ph.D., at Stanford University, where Wang recently completed her postdoctoral research. Working with mouse models, Wang engineered a protein-based tool called FLARE that was able to tag neurons firing during a defined time period. Preliminary studies of that tool have been encouraging, and Wang is eager to further improve the technique.
In a second exploratory line of investigation, Wang plans to develop regulatable nanobodies that can perturb specific protein molecules within cells, to improve research techniques for studying protein functions.
“Wenjing’s research could have far-reaching effects across many fields, by providing a powerful new set of protein-based tools for probing the function of complex biological systems,” says LSI Director Roger Cone, Ph.D. “She brings an outstanding research program that is emblematic of the type of collaborative research we want to continue fostering at the LSI and across U-M.”