An Unremarkable Fish Provides Remarkable Insights into the Human Digestive System

Assistant Professor of Biology Ken Wallace is in the fourth year of his study on the development of digestive system neurons. Wallace’s research is funded by a $238,500 grant from the National Institutes of Health’s National Institute of Diabetes, Digestive, and Kidney Diseases last year.

“My digestive research is interesting because while a lot is known about the physiological aspects, less is known about the genetic aspects. It’s an understudied system, which makes it both important and fascinating to look at,” says Wallace.

Wallace's research focuses on the development and genetics of the enteric neurons and smooth muscle layers that surround the intestine. These are the neurons that initiate and maintain the movement of waste and food through the digestive tract in many species, including humans. Problems with these neurons can result in many common digestive diseases that cause numerous health issues. In serious cases when neurons are absent, the muscle is not active and passage through the digestive tract is severely limited.

In order to study this system, Wallace uses zebrafish, a vertebrate species commonly found in pet stores. Over the past decade, zebrafish has become a major vertebrate model system because of its ease of genetic manipulation and because embryogenesis occurs over the course of five days in an externally developing transparent embryo. It also provides a model of the human digestive process, which means information that researchers learn about the zebrafish digestive system is translatable to humans.

“In many different species, the same genetic pathways are used as organ systems develop, including humans," explains Wallace.

Not only does Wallace use the zebrafish in his research, he raises them too. “We raise the zebrafish to produce embryos because this gives us the material that we work with,” he says. “After embryos are fixed at different developmental stages, we can detect gene and protein expression and visualize it under the stereomicroscope or a fluorescent compound microscope.” The research also involves injecting the embryos at different cell stages to alter protein expression or cause specific defects by inhibiting a specific gene or signaling pathway.

Wallace’s study is especially relevant because there are many human digestive diseases whose genetic origins are not completely understood, including Hirschsprung’s disease, a congenital disorder of the intestinal neurons that affects approximately one in every 5,000 live births. With his research, more can be learned about the origins and possible cures of these genetic digestive diseases.

Wallace shares his lab and study with four students — three undergraduates and one graduate student. He says, "They work with me on a regular basis. I give them their own projects within the study and they get to try to figure out the next step." This makes for solid research as well as great learning opportunities for students. "I’ve learned many techniques that I wasn’t familiar with before, like using a fluorescent microscope, and embedding and sectioning zebrafish embryos," says graduate student Tanveer Ahktar.

Wallace has been teaching at Clarkson for four years. He received a Ph.D. in molecular genetics from Ohio State University and completed his postdoctoral work at the University of Pennsylvania. In addition to conducting research labs with students, Wallace teaches comparative vertebrate anatomy, molecular and cellular biology, and developmental biology. When he’s not teaching or researching, Wallace chairs the animal welfare committee and organizes the seminar series for the biology department.

Wallace also hopes that the study will continue on even after his three-year grant is finished. “My research will always extend further and further into the future. There’s always more to learn,” he says.