Martha Bagnall leads an NIH grant investigating neuromodulators with collaborators at four other universities.
The Jeffrey T. Fort Neuroscience Research Building was designed to bolster the collaborative spirit of Washington University School of Medicine in St. Louis‘ groundbreaking research focused on the many mysteries of the brain and the body’s nervous system.
Martha Bagnall, PhD, an associate professor of neuroscience in the Department of Neuroscience, is taking that collaborative spirit internationally with a new National Institutes of Health grant that involves researchers at three U.S. universities and the University of Edinburgh in Scotland.
Bagnall is leading the $5.2 million grant further exploring neuromodulators, including dopamine and serotonin, and their effects on spinal circuits for movement managed through the National Institute of Neurological Disorders and Stroke. While previous research shows neuromodulators, which are chemical messengers released by neurons that regulate other neurons, can affect movement through spinal cord activity and output, much is unknown about their natural functions and targets. Bagnall and her collaborators will attempt to measure where and when these neuromodulators are released in the spinal cord during movement. They will use genetic tools to see exactly what types of neurons respond and block the effects of these neuromodulators to study how movement is changed.
“Earlier work used pharmacology to change neuromodulators everywhere throughout the spinal cord, for long periods,” Bagnall said. “But under normal conditions, we would expect these neuromodulators to be released in a more targeted fashion. Until now, we haven’t had a way to measure that. New fluorescent indicators, developed by several labs, have changed that landscape. Now, we can image the spinal cord and see exactly where these neuromodulators act and when. We’re aiming to put together that type of experiment, along with our deep knowledge about spinal cord motor circuits, to understand how neuromodulators are acting — where and why.”
A new tool developed by a grant collaborator, Duke University’s Mike Tadross, MD, PhD, allows for the selective blocking of the neuromodulator receptors in genetically targeted cell types, taking the group from observation to manipulation to understand what changes these neuromodulators cause.
The other collaborators on the grant include Adam Douglass, PhD, University of Utah; David McLean, PhD, formerly with Northwestern University but now at the University of Edinburgh; and James Murray, PhD, University of Oregon.
“These moments of discovery deliver glimpses, and we get something new that no one else knows.”
Martha Bagnall, PhD
Collaboration provides several benefits, Bagnall said, including introducing new skills, resources and ideas.
“Across these five labs, we’ve all read a few of the same papers, but collectively we’ve read a much wider scope of the literature, so we can ask more informed and deeper questions if we work together,” she said. “And collaboration builds community. The people in my lab will have a chance to work with and communicate with the people in these other labs, developing working relationships and broadening the community we consider ours.
“This work will rely on several graduate students, technicians and postdocs in my lab as well as others. An important thing we do is train the next generation of scientists. The individual discoveries of science, exciting though they are, are generally less important than the community that we build of people trained in thinking rigorously, creatively and thoughtfully about science — and then in doing those experiments.”
When first approaching the grant, Bagnall looked for collaborators who would push boundaries and find something new and creative. She’s previously worked with McLean and met the others through conferences, such as Douglass, with whom she discussed science during a post-conference train ride.
“Collaboration is important because scientific research can be isolating working on problems with a small group of people,” Bagnall said. “At the bench, you are by yourself, grappling with your data, theory or puzzle. The work can feel isolating. It’s great to have a lab of people to discuss and then — with a grant like this — to extend it across more territory. More people are puzzling over shared questions.”
The grant also represents a new direction for Bagnall’s lab, which studies how sensory information about orientation and movement drives appropriate body movements to adjust posture. Using the new fluorescent tools for visualizing neuromodulators, Bagnall is approaching the established research with a fresh outlook while drawing upon her background in spinal neuron function and the descending control of motor circuits.
“Research is a chance to discover new things,” she said. “The whole excitement of science is studying what others have for years and decades and looking at what we know and don’t know. You can push on this small little corner and find something. Or you can push that boundary a little farther out. It’s gratifying. It’s a lot of troubleshooting, but these moments of discovery deliver glimpses, and we get something new that no one else knows.”