'Second brain' research collaboration helps shape the future for DO-PhD student

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Scientists and physicians alike have long said that we don’t fully understand how the brain works. New research from Brian Gulbransen, an MSU Foundation Professor in the College of Natural Science’s Department of Physiology and Mustafa Ahmadzai, a seventh-year DO-PhD student in the College of Osteopathic Medicine, may provide new clues.

The pair’s paper, published this month in the Proceedings of the National Academy of Sciences, looked at the enteric nervous system, which is often referred to as the “second brain” in our gut. Most people are familiar with neurons, which carry signals throughout the nervous system via electrical activity. But together, Gulbransen and Ahmadzai discovered more about the true role of glia, a type of cell that was once considered a passive player in both the central and enteric nervous systems.

Their work reveals that glial cells play a more important part than once thought by modulating signals in the enteric nervous system’s signaling network. Glia don’t drive the signals, per se, but they impact the delivery of those signals in meaningful ways. These insights may present new opportunities to treat gut disorders, and may even provide hints at how some less-understood aspects of brain signaling work.

Ahmadzai, the paper’s lead author, sees this research as the result of both his DO-PhD education and his natural tendency to ask questions. After starting in the MSU College of Osteopathic Medicine DO program, he realized he missed the research work he did in his masters degree program. When working in clinical settings, Ahmadzai found himself inclined to ask “why.”

“Even if there was something that we did as a standard of care, I looked it up on my own. So there was always that tension to investigate,” he explained. Eventually, Ahmadzai transferred to the DO-PhD program, which currently has 43 students.

Ahmadzai wanted to join Gulbransen’s functional physiology lab back when he initially started the program, but there was no space. Luckily, a year later when Ahmadzai had finished his clinical rotations, a space had opened up.

For his part, Gulbransen says DO-PhD students bring a special skill set to the table in his lab. “They’re the kind of people who are going to jump in, really get in there, answer the questions, and do a great job. They bring fresh ideas to the field. I think the perspectives they bring are unique, and it's really driven the research forward.”

Driving the field of medicine forward is a primary motivation for Ahmadzai. “What really compelled me to transfer to the program is something I think is unique among DO-PhDs. It’s this feeling that I have something to contribute that could fundamentally alter clinical care. Real change and real revolution in medical care comes from the interface between clinical practice and research. To me, that is really powerful.”

Above all, this paper wouldn’t have been possible without a strong mentorship relationship, Ahmadzai said. “Brian's an amazing mentor because he always gives me intellectual latitude. But he also brings me back down to earth and says, ‘Okay, how do we distill this into very well-dissected questions?’”

As for what’s next, Ahmadzai has completed his PhD and is in his final year of medical school. At the moment, he’s interviewing for residency programs in anesthesiology, an area of medicine where he sees a lot of opportunity to contribute. “To me, it’s the interface between every domain of medicine and that functional aspect of physiology. You modulate human physiology, you have a very hands-on role, and it's a service profession, so you interact with every domain of the hospital.”

In this way, he hopes to continue working on neural networking research. “I keep thinking, if this is how complex it gets in the enteric nervous system, what about the brain? How can we even conceive of having models of artificial intelligence if we don't really understand the role of glial cells? We have so much of an incomplete picture that I think a lot of what we conceive as consciousness research is probably still in its infancy,” Ahmadzai explained. As a dual degree graduate, he looks forward to working with patients so he can take his observations from those clinical settings, ask good questions, and use his basic science background to investigate them in a laboratory setting.

Meanwhile, Gulbransen and his team will follow up this paper by studying networks of neurons and glia change after inflammation, which is one of the main factors that drives changes in GI motility and visceral pain. “The thought is that these networks of neurons and glia in the gut become remodeled somehow by episodes of acute inflammation,” Gulbransen explained. “We think that understanding how these networks of neurons and glia change will give some kind of insight into the mechanisms that drive gastrointestinal disorders like IBS and IBD.”

Aside from a strong mentorship relationship, Ahmadzai believes the supportive, collaborative environment in Gulbransen’s lab played a huge role in his success. “They say a supportive environment is important, but what’s often overlooked is what a supportive environment actually looks like,” Ahmadzai pointed out. “A supportive environment isn't one where you're worried about asking a question because you’re afraid of how it might make you look. You're allowed to speak your mind. And that's a prerequisite to being able to ask compelling questions.” His advice for graduate students in general: “Find a place where you know you'll thrive as a person, where you'll be happy, where you'll be allowed to grow.”

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