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Research with a backbone

Tanner Conley

Staff Writer

A University of Wyoming professor is spearheading research that could potentially lead to the end of paralysis, by studying one peculiar fish.

Karen Mruk is an associate professor who was originally hired to teach pharmacology, but has since turned her attention to something that impacts between 250,000 to 500,000 people every year across the world according to the World Health Organization (WHO).

“I grew up in New Jersey and I got my undergrad degree at Drew University. Then I went and worked for Revlon for a year and a half. I was a chemist and I made hair products. I decided to go back to graduate school [because] my work wasn’t intellectually stimulating for me. I went to grad school at UMass Med [and] I studied ion channels. Then I did my postdoc at Stanford and studied zebrafish there. Then I came here,” said Mruk.

But what is a “zebrafish” and how is it supposed to be the key to unlocking the mysteries of spinal regeneration?

The zebrafish is a type of minnow that derives its namesake from five stripes that run horizontal along its body. The stripes tend to be blue which, when compared to their silver bodies, gives the impression the fish have a similar camouflage to a zebra. They can be found typically in freshwater habitats in South Asia and range as far north as the Southern Himalayas. These fish typically do not exceed 1.5 inches in length but can reach up to 2 inches depending on conditions.

So how can a tiny fish have such a big impact on the human world?

“Zebrafish have a huge advantage compared to a lot of the other models. The first is that they are vertebrate; they actually have a backbone like we do and that means they also have myelin like we do. If you are interested in the nervous system, the structure of their nervous system is pretty identical or pretty close to human structures. So that makes them a really nice model for studying human problems. The second big advantage is that they are transparent when they are young, so you can actually see through them. You get to actually see these organs develop and if you injure them you get to watch them regenerate in real time,” Mruz said.

Much of Mruz’s research revolved around the similarities between the structure of the zebrafish and the human form. These similarities extend to the genetic level as well.

“The third big [advantage] is that they have been sequenced. They are genetically tractable, so we can tell what their genome is, they are 80% homologous to humans, so genetically we can knock out a gene that we know is an issue in humans and see what the phenotype is and see how we rescue or treat that. They are just super easy to work with, much easier than mice in my opinion,” Mruz said.

Mruz, like many professors, guides the research of many students. One unique advantage she possesses is the advantage of program diversity within her lab.

“It’s really great because I get to have students from everywhere. I have one student from chemical engineering, a student from chemistry; I have a student from microbiology. You name it; they are probably here in the lab. I really like that I get that diversity,” Mruz said.

For Mruz, the culmination of her research comes in the form of simple improvements to people’s lives who have been afflicted.

“For humans, I think if you talked to doctors, they would say the goal for humans is that they get some of their quality of life back. We may not ever fully cure paralysis, but if we can give them better control over their bladder or temperature and heart rate after an injury, that would improve their quality of life substantially,” Mruz said.

But like any other research project, nothing is certain.

“From a fish perspective, one of the really interesting things about fish is that they regenerate almost everything, but in terms of the spinal cord, they regain their ability to swim before they fully regenerate it. That’s very much unlike a human, which doesn’t regenerate at all. So, if we can tap into understanding how they recover their function, we can make better progress on getting patients a better quality of life. That’s the overarching goal. Will it happen in my lifetime? I don’t know,” Mruz said.

But upon achieving her research goals, Mruz is well prepared for the future.

“Say we cured paralysis, one thing that we are really interested in understanding is if you have an injury, but there are other ways of injuring your spinal cord. You could have MS, ALS or Lou Gehrig’s disease…We are interested in understanding how those mechanisms change. Do you respond to being shot or stabbed differently than if you lost your myelin? Differently than if your neurons die because of a genetic disorder? If that’s true, do you recover the same way afterwards? Is there anything we can learn from spinal cord injury that we can then apply to something more neurodegenerative? The majority of brain disorders have an electrical component. So then can we take some of the stuff we’ve learned about the electricity of the circuits, and apply that to those kinds of diseases?” Mruz said.

While the future may be uncertain, one thing is clear in the present: this little fish could have a massive impact on the future of humanity.

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