University scientists are using a seemingly unlikely animal to study development, cell function and the effects of debilitating human diseases.
The library of fish tanks can be found down a flight of yellow and red stairs, in the Lokey Science Complex.
Danio rerio (zebrafish) are tiny, striped fish with astounding capabilities for research.
These shiny little fish, miles away from humans in terms of physical description, are remarkably similar to us in many ways.
First and foremost, zebrafish are vertebrates — they have a backbone. They also have eyes, blood, a digestive tract, a pancreas and many other similar features to humans.
Ninety percent of zebrafish’s amino acids are in the same order as a human’s. Because of these similarities, zebrafish make excellent model organisms for research on human diseases.
Zebrafish are small, relatively easy to breed and don’t require excessive luxury. The lab I visited housed around 70,000 zebrafish, in rows and rows of stacked tanks. Thousands of mutant strains of zebrafish are kept on liquid nitrogen in the bowels of building — if anyone needs a particular mutation, all he needs to do is thaw the sperm and fertilize an egg in vitro. The zebrafish sperm can last years on liquid nitrogen, so researchers have access to mutations whenever they need them, as more discoveries are made.
Some mutant eggs are fertilized in vitro, meaning “in the glass,” or in a Petri dish. Once the egg is fertilized, the researchers use micro-needles to inject molecular agents, such as proteins, into the egg that will help “mark” what areas or aspects of the mutant strain are different than the wildtype (or “normal”) zebrafish. This will make it easier to see what exactly is going on in a mutant fish.
John Postlethwait, professor of biology and principle investigator at one of the zebrafish labs on campus, offered a good analogy for what investigating the effects of a mutation is like:
Suppose you’re exploring the inner workings of your car and you find a mysterious wire that doesn’t have an obvious function. How can you find out what that wire does? Cut it. Then do some testing. Do the brakes still work? The lights? The air conditioning? The engine? If all those answers are yes, than that wire doesn’t affect those functions of the car. But if you discover that the windshield wipers are no longer wiping, it’s very likely that was the wire’s purpose. The same can be applied to genes. Mutate a gene in a growing zebrafish, and see how the embryo develops.
“Clearly that is something that you cannot do on intact people,” said Postlethwait.
How is this research relevant to University students? Consider the disease Fanconi Anemia (FA). It’s a very rare genetic disease that causes early bone marrow failure and disrupts the production of red blood cells (your body’s oxygen delivery service), white blood cells (the warriors of the immune system, fighting diseases) and platelets (the healers that help form blood clots). This disease also raises the likelihood of getting cancer or leukemia 1000 fold.
“There are 14 genes that cause FA when mutated in humans. All of those genes are present in zebrafish,” Postlethwait said.
In the lab, researchers can study the effects of certain mutations in the genes that cause FA and can investigate possible treatments. Zebrafish with FA get submersed in “drug baths” containing drug-like molecules and look for the substances that “rescue the DNA repair defect.”
“Such compounds become candidates for substances that might be developed into human therapeutic agents,” said Postlethwait.
Generations upon generations of zebrafish are raised in these labs, being cared for by a team of scientists, graduate students and undergraduate students. Sophomore Jessica Butt, a marine biology major, took me to work with her one day so I could see the lab for myself. As she went down the lines of fish tanks confirming the correct number of fish were actually in each tank, I explored the lab and got a tour from Tim Mason, the facility manager. He showed me the room where they keep the frozen sperm, both procedure rooms where fertilization and injections are done, and the nursery, where the baby fish hatch. My inner child was a little disappointed when I found out baby zebrafish feed on brine shrimp — more commonly known as sea monkeys — though it was cool to see the little orange sea monkeys in the transparent stomachs of the tiny baby zebrafish.
Once again I was left in a sense of awe as I stared at a tank containing 18 fish, all of whom were trying desperately trying to swim through the plastic wall at me (they probably thought I was there to feed them). The research that is being done on these tiny little fish can create enormous changes in the world of developmental biology, medicine, and even in the study of toxins. The study of zebrafish is a revolutionary model for research developed at the University by George Streisinger. It started off as a side project that became the new standard for research.
“You can make a lot of discoveries about a fish that have to do with humans,” Mason said. “All for the greater goal of human health.”
[email protected]