Model Redefined

A model organism doesn’t just mean a mouse or fruit fly anymore.

Nipam Patel didn’t set out to study the tiny gray crustacean Parhyale hawaiensis, otherwise known as the beach hopper; he was trained in fruit fly neurobiology. But as the University of California, Berkeley, professor dug deeper into the evolution of arthropods, he realized that he needed to go beyond the fruit fly if he wanted to understand how different arthropod limbs are created and organized.

“We know that basic principles are incredibly well conserved [among species]. If that’s true, how do you generate the kind of diversity that we see?” Patel says. “Looking at just one organism you know you are not getting a complete view.”

Patel, an HHMI alumnus investigator, is just one of an increasing number of scientists who are moving beyond traditional lab research models to find organisms that can help illuminate the larger commonality and diversity of nature. He served as an editorial advisor on a two-volume series called Emerging Model Organisms, a lab manual recently published by Cold Spring Harbor Press that tells scientists how they too can use some of the models drawing current interest. A few examples: amoebas, comb jellies, spiders, quail, turtles, and even yams.

Thousands of scientists focus on traditional organisms, such as mice, roundworms, and fruit flies. A lab group studying a less common organism, on the other hand, may be one of just a handful that, like Patel’s, finds a model that might help investigate a particular research question. But they can be enthusiastic evangelists for the merits of their organism.

“I really admire the scientists who work on these funny animals,” says Richard Behringer, a developmental biologist at the University of Texas M.D. Anderson Cancer Center who was also an advisor on the Cold Spring Harbor books and recently started studying reproduction in bats. “They often work with little or no funding, which makes them very efficient. They persist because they love it so much.”

Behringer, who does research on the early stages of reproduction and embryonic development, has spent his career studying mice but recently added bats and wallabies in an attempt to get at some of the universal rules of reproduction.

His most recent study subject, the short-tailed fruit bat, is more humanlike than a mouse. Its uterus has the same basic structure: it menstruates and usually has only one pup. The mouse, on the other hand, has an estrous cycle but does not menstruate, a uterus divided into two long tubes, and large litters. The Tammar wallaby’s reproduction is completely different. Whereas humans and many other mammals create a two-part blastocyst, the preimplantation stage of an embryo, marsupials like the wallaby deviate from the start. Yet they still successfully create an embryo.

“What is clear is that the classic model organisms provide a sort of template,” Behringer says. “You can look at your animal and see how it compares.”

Patel is doing just that with his beach hopper, which a graduate student looking for crustaceans to study found living in a filtration system at the Shedd Aquarium in Chicago. Right away, he discovered that the hopper had the most important characteristic for any new model: it is easy to raise in the lab. It also has a reasonable generation time, reproduces prolifically, and eats almost anything.

Patel has been surprised by the differences he has found between his traditional fruit fly model and the beach hopper. For example, beach hoppers can replace their germline cells—those cells that pass genes from one generation to the next as sperm and eggs—after embryo formation and development, which fruit flies are not able to do.

“Maybe it’s not that unusual—we don’t know because we haven’t gotten to that level of detail in many species,” he says. “But it has remarkable properties we had not anticipated.”

Those surprising findings are just what scientists studying these newer organisms hope for. Many lab research animals are being called “models” to illustrate their potential to help scientists understand human disease. But many of their reasons for studying these animals have “nothing to do with humans whatsoever,” says Steve Klein, program director in the developmental systems cluster in the National Science Foundation’s biology directorate. “Studying additional, and more appropriate, animals will tell us what we want to know, fundamental universal principles: How do cells communicate? How do they migrate? How do they differentiate?”

The organisms that have become standard lab models were not chosen because they have any specific connection to humans or are particularly representative, explains Rudy Raff, a professor at Indiana University who has written about models and studies sea urchins in his own lab. “[The standard animal models] are special ones—easily raised in the lab, amenable genomes, fast reproduction. For example, Drosophila is not a typical insect.”

Raff advocates moving beyond calling any lab organism a model. “What are we modeling, exactly? It has become a cliché.” And saying that an animal is a model gives the wrong impression to nonscientists, who sometimes still think of a model organism as a replica of humans or human disease, Raff says.

“We need to get away from the idea that the only biology that is worthwhile is biology that is related to medicine,” he says. “If we are liberated from that restraint, it gives me hope that we can examine a broader swath of nature.”

-- Andrea Widener
HHMI Bulletin, November 2011

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