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More Than Just Lab Rats: Researchers Extol Their Model Organisms

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More Than Just Lab Rats: Researchers Extol Their Model Organisms

More Than Just Lab Rats: Researchers Extol Their Model Organisms

By Catherine Kolf

August 2013–If there were a satisfaction survey about the model organism you study, how would you rate it? If our unofficial, random survey (n=5) is at all representative, most of the basic science researchers at Johns Hopkins would be “very likely” to recommend their model organism to undecided graduate students.

Erin Goley on Bacteria

Erin Goley, Ph.D., is an assistant professor of biological chemistry who works on a little-known bacterium called Caulobacter crescentus. She chose it because the bacterium is particularly well-suited for studying the protein fibers that crisscross inside cells, giving shape, providing structure and acting as “train tracks” for moving cellular machinery from one place to another. She first studied these protein fibers, known collectively as the cytoskeleton, during graduate school. She was mostly studying purified proteins from human cells. But it was around the same time that scientists discovered that bacteria have cytoskeletons, too, although not all bacteria have all three types of protein fibers that make up the cytoskeleton in human cells.

caulobacter C. crescentus

In her postdoctoral work and in setting up her own lab here at Johns Hopkins, Goley chose to study C. crescentus because it does have all three types of protein fibers. And not only are bacterial cells simpler than animal cells, they also yield a more complete picture in the sense that each cell is a complete organism. Plus, it’s easy to do a screen of their entire set of genes because they have so few of them (relative to higher organisms, at least).

Did you know?
C. crescentus makes the most of its nutrient-limited environment by dividing asymmetrically. A single bacterium will swim through its surroundings until if finds sufficient nutrients for growth. It then attaches to its surroundings through a stalk capped with “holdfast,” a sticky substance thought to be the strongest adhesive in the world. A “daughter cell” then splits off from the stalked cell and swims away, using a whip-like tail, to find another nutritious environment where the cycle can begin again.

When funding is tight, Goley says it can be harder for C. crescentus researchers to get grants because grants tend to first go to labs that study disease-causing bacteria.

Debbie Andrew on Fruit Flies

fruit fly

Deborah Andrew, Ph.D., a professor of cell biology, studies the formation of the trachea and salivary glands during fruit fly development. If you took a college-level genetics class, you may have had the experience of working with fruit flies. If so, the most vivid memory of that experience might have been the pervading smell of ether, used to put the flies to sleep so that they could be examined under the microscope. Andrew says that most research labs haven’t used ether for a couple of decades now: Carbon dioxide works even better and it’s odorless and nontoxic to the flies. Andrew switched to carbon dioxide in the middle of her postdoctoral research.

Andrew has been working with Drosophila melanogaster since graduate school. She particularly loves discovering things in Drosophila that no one has seen yet in other organisms. “Drosophila is well-suited to discoveries,” she says, “because their genetics are less complex than higher organisms. If you delete a gene in a mammal, for example, there may very well be other genes that can compensate for it, masking the true function of the gene. In Drosophila, the effects are generally much more clear.”

The tools available to Drosophila researchers and the huge, generous Drosophila scientific community are also perks, according to Andrew. “Everyone shares all of their genetic tools, protein-visualization tools and tricks of the trade,” she says. “And you can’t beat the ability to photograph live flies!”

Did you know?
Andrew explains that “for every four or five related genes in humans, there are usually only one or two equivalents in flies, so Drosophila is a very clean model organism. It’s not as simple as a single cell, but it can answer a lot of questions that can’t be answered in humans.”

You do have to be OK with a few escaped flies keeping you company as you work.

Michael Parsons on Zebrafish

Michael Parsons, Ph.D., is an associate professor of surgical oncology with the McKusick-Nathans Institute of Genetic Medicine who works with zebrafish. He is trying to decipher the molecular chain of events that causes insulin-producing beta-cells to develop in the pancreas. Because beta-cells don't function properly in diabetes, learning how zebrafish make them could teach us how to make them from human stem cells to treat diabetes.

“You have to ask the right questions of the right organism,” says Parsons. “We can do a drug screen of thousands of compounds, each at seven different doses with each dose tested on 16 different fish to find out which is best for a particular task. You can’t do that in many other organisms.” At least you can’t do that in any other organism so similar to humans, and Parsons wanted to work on something not too far from clinical application.

These little vertebrates are also small and transparent enough to be photographed well, and they have the advantage of developing outside of their mothers’ bodies, allowing continuous observation. The genetic tricks available for working with them are quite robust, too. For example, genes can be tweaked so that each protein they produce will glow, showing researchers where that protein is in the organism.

Did you know?
“Zebrafish can regenerate almost every body part, even parts of the heart,” Parsons says. “What do they have that we don’t?!”

Parsons can study beta-cell development in zebrafish that have been genetically engineered so that all of their beta-cells glow. However, it is hard to study the effects of diabetes in zebrafish, as they never remain diabetic for long. If you injure the pancreas of a zebrafish, it will simply regenerate and repair itself.

Julie Watson on Mice

Julie Watson, M.A., Vet.M.B., D.A.C.L.A.M., is an associate professor of molecular and comparative pathobiology and director of the rodent clinical programs. In other words, it is her responsibility to keep all of the research rats and mice at the Johns Hopkins University School of Medicine healthy. No small task.

Almost any enterprise that involves a large number of animals must employ veterinarians to help maintain the health of the “herd.” In this case, instead of protecting a herd of cattle, Watson’s job is to identify and treat new threats to the health and safety of our rodent herd. “My work is herd health on steroids,” she says. “It’s an amazing opportunity to study herd health under very controlled conditions.”

Did you know?
Mice are nocturnal, so their behavior can only be monitored in the dark. Bring your night-vision goggles and keep the lights off if you want to see any scurrying.

One of Watson’s biggest challenges comes from teeny, tiny parasites called fur mites. They’re microscopic so you can’t just go through a mouse’s fur with a fine-toothed comb to find them, and flea collars aren’t a good option either. They don’t seem to bother the mice too much but they can occasionally cause a rash. “Ideally, research mice are not battling anything unknown that could alter the results of someone’s research,” Watson explains. “We’re working hard to identify fur mite contamination and find a way to combat them.”

Bob Adams on Anything-Bigger-Than-a-Rat

Robert Adams, D.V.M., is the associate provost for animal research and resources and an associate professor of molecular and comparative pathobiology. He’s been at Johns Hopkins for a long time, caring for an ever-greater number of research animals of a wide variety of species.

“The choice of an animal model depends mostly on the scientific question being asked,” he says. “Cost is also a factor but not the strongest. And then there is how easy the animals are to care for and work with. Some of the animals bite, and bite hard.”

“As science progresses, it naturally moves its questions into the lowest species possible for answering the question at hand,” he says. “In the ‘60s and ‘70s, surgeons were just learning how to transplant organs— hearts, lungs, etc. Mice wouldn’t have been very useful there, but nonhuman primates weren’t necessary, either. Dogs were big enough and easy to handle. Now, those questions of ‘plumbing’ have been solved and the issue is immune rejection, where smaller animals like mice may work just as well.”

Did you know?
At Johns Hopkins, almost 90 percent of the research animal population is mice.

Sometimes the best model organism for a disease is not an easy one to work with. For example, the hepatitis B virus doesn’t generally infect mammals … except groundhogs (and humans). Punxsutawney Phil might look cute, but he also has some serious claws and two big front teeth. (No, we don’t work with groundhogs here.)