Small fish are providing a big research opportunity for students at the University of Wisconsin-Superior.
Assistant professor of biology Jenean O'Brien is using zebrafish, which can be found at almost any pet store, to research the role two genes play in the development of rhabdomyosarcoma, a pediatric muscle cancer.
The striped tropical fish that grow up to 2 inches long have similar genetic structure to humans. They have high reproduction rates, develop quickly and embryos are transparent. That allows researchers to study tumor development closely, especially when those tumors are manipulated to glow green.
O'Brien has been building up the research project since she was hired in 2015.
"It's a necessary component to learning to be a scientist, to do hands-on research," she said. "I just think if you're going to learn science, you should do science."
The UWS biology department is historically strong in environmental research, but O'Brien's expertise is in health and molecular biology fields. The cancer study gives students interested in health-related careers an opportunity to focus on research that's more relevant.
"I know way more about cancer now than I ever imagined," said senior Aaron Clark, an independent study student in the lab who is double majoring in biology and broadfield science. " And if I do apply to medical school, it looks way better on my application than if I was studying plants for a year."
Both he and Kim Kobar, a UWS graduate who works as a research assistant for O'Brien's project, said they are now torn between becoming doctors or researchers.
"It started off just being a cool interest and we had to do some sort of research, but it kind of turned into a passion," Kobar said. "It's very interesting working with the fish. It's super cool to see kind of how everything develops and how all these techniques work."
The first zebrafish embryos were injected this week, after years of preparation.
"It's very exciting," Kobar said.
Manipulating fish genes involves injecting the right coding into the DNA of one-day-old embryos.
The student researchers first remove one of two genes from the fish. One is found in greater concentration in tumors and may promote cancer growth, the other is less concentrated in tumors and may help inhibit cancer growth. Then they will inject a code to induce mutation in a different gene to cause tumor growth, adding instructions cribbed off jellyfish that will make the cancerous cells glow. A similar process, minus the mutant gene, is used to give the neon fish found at pet stores their glow.
"Our tumor model will make fluorescent green tumors," O'Brien said.
About 10 students will perform independent study work on the project annually, and two to three students will be employed to feed the fish and check water chemistry. The cancer research project was just awarded a three-year, $250,000 grant from the National Institutes of Health, which will provide stipends for three student fellows each summer and help pay for salaries and supplies.
Getting to the first injection has been a journey.
The first year was spent creating the fish habitat. A new system to house the fish would have cost $20,000, but UWS biology professor Ed Burkett and a student built one from scratch for $2,000. University of Minnesota Duluth biology professor Jennifer Liang donated the tanks for the fish.
The next year was spent with benchwork — working with DNA, genotyping the fish and becoming familiar with molecular biology techniques.
When the grant was announced this summer, research ramped up. Kobar got the injector up and running and started breeding fish. Faced with low egg numbers and few successful pairings, she tweaked lab conditions to encourage breeding. By warming the room temperature, dimming the lights and feeding the fish more, their success rate soared.
"We're getting more tanks to lay, and when they do lay we're getting more eggs," Clark said.
Now, the research can begin.
The two genes the UWS project focuses on come from a gene family that contributes to at least 10 different types of cancer, O'Brien said. She worked with them in relation to breast cancer while doing post-doctoral work at the University of Colorado.
They also transfer well to zebrafish while being relevant.
"The gene sequence for our tumors is the human gene that causes tumors," O'Brien said, but it can be induced in fish.
Gearing up for the cancer research, and securing the grant, has involved working hand-in-hand with the local research community. While the results are still unknown, the journey is just as important.
"I chose a school that has a small campus because I want to give students one-on-one access to research," O'Brien said. "Their education matters to me. I didn't choose a campus where I would be doing full time research. I like teaching, I like shaping the next generation; I like providing experiences for children to figure out what's out there and how it works."