Stowers Institute for Medical Research
Kansas City, MO
Nicolas Rohner, Ph.D.
Assistant Professor, Department of Molecular & Integrative Physiology
The University of Kansas School of Medicine
It is rare that one sheds light on matters of fish genetics and medieval history simultaneously. This feat was, however, accomplished by Stowers Assistant Investigator Nicolas Rohner when he was a Ph.D. student in the lab of Christiane Nüsslein-Volhard at the Max Planck Institute for Developmental Biology in Tübingen, Germany.
In 2009, Rohner co-authored a Current Biology paper reporting that in zebrafish, a gene called Fibroblast Growth Factor Receptor 1 is necessary for fish to develop scales. It turns out that monks in the Middle Ages bred carp to lack scales, making meal preparation less laborious. Rohner’s work shows precisely what genetic mutation emerged during the monks’ domestication of carp, a historical tidbit that Rohner savors as much as the science itself.
“People in the Franconia region of Germany are obsessed with carp,” he says, marveling that Americans don’t appreciate this delicacy. “It is very rewarding that I ended up finding the genetic basis for why a fish that nearly everyone in my hometown eats has no scales.”
Currently, Rohner’s research centers on investigating why vertebrates, and fish in particular, exhibit such diverse traits. However, basic research in developmental biology hasn’t always been at the forefront of his scientific interests. As an undergraduate at Friedrich-Alexander University (FAU) near his home in Erlangen, Germany, Rohner considered a career in applied science. In 2002, he earned a BS in biology and pursued postgraduate studies on antibodies targeting leukemia cells.
Upon receiving his MS in 2005, he sought a different challenge and decided to pursue a doctorate in developmental biology, despite the fact he’d never had a class in it. In particular, he found zebrafish to be an attractive model system. “I’d always had fish in a tank as a kid,” he chuckles. “I knew zebrafish would be easy to maintain - they were always outliving the other fish in my tank!”
His Ph.D. work confirmed that fish were a great model system for studying evolution, so he embarked on a postdoc in the lab of developmental biologist Cliff Tabin, Ph.D., at Harvard Medical School, where he focused primarily on the genetics of the cavefish Astyanax mexicanus.
Cavefish exhibit two seemingly strange traits: the adults lack eyes (which are dispensable in a cave) and the fish may feed only once a year–feasting when food is available. The question was, how had the cavefish adapted to nutrient-poor conditions that would easily starve a carp or a zebrafish?
To answer this question, Rohner undertook a genetic screen that revealed that unlike “normal” fish, cavefish had a mutation in a gene for a receptor called MC4R, apparently allowing them to binge eat to the point of obesity. That work was published this year in the Proceedings of the National Academy of Sciences. In normal fish, intact MC4R likely serves as a satiety signal that cavefish lack. Intriguingly, the human counterpart of MC4R is mutated in some forms of inherited obesity.
An additional cavefish curiosity is that weight gain is a positive, not a health risk as it often is in humans. “Cavefish are healthy and live a long time, despite having high body fat levels,” says Rohner. “Maybe this will lead to insights on how individuals with high body fat levels can also be healthy.”
As a postdoc, Rohner also published a newsworthy Science paper in 2013 relevant to a concept biologists called “canalization,” which—in short—proposes that organisms can harbor traits in their genome that remain masked until needed.
Case in point: cavefish ancestors clearly did not become “eyeless” the day they wandered into a cave. Their very existence in fact suggests that their sighted ancestors might have harbored hidden mutations that would allow eye shrinkage if necessary.
The idea that organisms are “prepped” genetically for environmental change is controversial, but Rohner conducted a simple experiment proving it is at least possible. He raised normal fish in water that contained a chemical that blocks a protein called Hsp90, a candidate “masking factor.” That manipulation, meant to simulate the stress of a dark environment, was enough to stimulate emergence of small eyes in offspring of treated fish.
Other researchers had proposed this mode of adaptation but Rohner says they lacked a “real world” example. “We provided the experimental evidence that if you perturb a system by stress, variation becomes visible,” he says. “How prevalent Hsp90 is in other evolutionary scenarios remains to be seen.”
In his lab at the Stowers Institute, Rohner studies the genetic basis of adaptation and speciation primarily in the cavefish model. He was drawn here primarily by the freedom to take risks in research: “I came in with what sounded like a crazy model system and the Institute has provided me the tools to develop it into an important one to help us better understand developmental biology.”