Adrian Rothenfluh: Faculty Spotlight
Jun 30, 2020 10:00 AM
Adrian Rothenfluh, PhD, MSc
by Kyle Wheeler
What do you get when a fly and a neurobiologist/geneticist walk into a bar? The answer may not be the punchline of a joke, but a reality that can teach us a lot about our brains. When it comes to intoxicated drosophila, Adrian Rothenfluh PhD, MSc is more the designated driver, looking for answers embedded within the brains of the drunk flies in his lab.
As noted in his research statement: "Dr. Rothenfluh's research focuses on the genetics of psychiatric disorders, especially addiction. His lab uses Drosophila to model various neuropsychiatric conditions and to investigate the molecular, signaling, and neuronal mechanisms that mediate behavior. His lab has a continued commitment to translate his findings to human studies."
Working at a unique intersection of human genetics and neurobiology with findings that have a translational impact on our understanding of psychiatry, Dr. Rothenfluh came to the University of Utah with his "better-half, looking for a place with a trajectory," they liked. At the University of Utah, they found a place where they've enjoyed the collegiality, collaboration, and can-do attitude characteristic of their colleagues.
Before finding his way to the University of Utah, Dr. Rothenfluh completed a Master's of Science in molecular biology at Universität Basel in the early '90s. He went on to complete a PhD in genetics at Rockefeller University, which he followed up with a postdoctoral fellowship at UC San Francisco. Dr. Rothenfluh subsequently spent nearly a decade as an assistant professor at UT Southwestern in Dallas, Texas before ultimately coming to the University of Utah in 2016. Throughout his career, flies—drosophila—have taken a leading role in Dr. Rothenfluh's research and findings.
As an outsider to Dr. Rothenfluh's vein of research, a natural question arises with the use of flies, particularly when it comes to understanding the human brain: why flies?
When discussing drosophila, Dr. Rothenfluh brings up world-renowned physicist, molecular biologist and behavioral geneticist, Seymour Benzer. He points to the observations Benzer made in noting that flies stand as a convenient intermediate step between the complexity of humans and the simplicity of yeast. That says nothing of the tremendous cost efficiency and scalability found in using drosophila.
Dr. Rothenfluh continues to cite Seymour Benzer's work as told in "Time, Love, Memory" by Jonathan Weiner. He notes that flies exhibit perhaps unlikely, albeit real similarities with humans in circadian rhythms—which Dr. Rothenfluh studied while working on his PhD—courtship, and learning and memory. Thus, flies become even more compelling test subjects for their translational relevance.
After noting that Seymour Benzer had many skeptics regarding the usefulness of studying flies and their brains, Dr. Rothenfluh notes how Benzer continues to be vindicated in his assertion that fly brains have translational worth. When talking about studying drosophila, Dr. Rothenfluh speaks in the modest tones of a scientist who defers to the data and says of flies that, "even though the brain looks very different, the logic and circuit organization of the brain may turn out to be more similar than we thought. I think both the combination of understanding the molecules as well as the logic of the circuits, might lead to more insights which might be somewhat translatable."
Image of a fly brain. The circle in the middle of Figure A is the ellipsoid body, a pre-motor center thought to be involved in alcohol tolerance.
Continuing to discuss translational application, Dr. Rothenfluh notes a recent publication he co-authored wherein the study led to the discovery of several new genes. But understanding the mechanisms of those genes is difficult. Thus, he says, "I think mechanistic validation, as well as mechanistic understanding of those molecules and genes is something that model organisms are really useful for."
Coming back to the fly as a drinking companion, Dr. Rothenfluh's research has shown tremendous promise in exploring addiction behavior through the study of flies. In his lab, they have found that much like humans, flies are initially averse to alcohol. He says with a smile, "people generally start out with low-percentage or sweet-tasting alcohol. And mice don't like it that much either. With mice, you have to literally sugar-coat it." He goes on to suggest one might naturally assume flies eat rotten things, so they must like alcohol. "It turns out, they don't. But this is brilliant because it is the same for us. It turns out that flies over time learn to like it."
Dr. Rothenfluh notes the perfection of this similarity. It is exactly what addiction is: "an experienced dependent liking." And with that addiction, there are two components. On the one hand, how sensitive are you
to the rewarding effects? And on the other, how sensitive are you to the aversive effects? Those who are more sensitive to the negative effects are less likely to become alcoholics. Embedded in this question is an unexplored frontier, which Dr. Rothenfluh has been studying. There is great promise in this area because of the potential to discover a way to make substances less appealing.
With a promising research frontier, Dr. Rothenfluh's work with flies will continue to be a compelling area of interest. So next time you swat a fly away from your drink, maybe consider sharing a sip and raising one to the tremendous work that Dr. Rothenfluh is doing.