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January 25, 2002, Special Edition

"Learning the Rules": Woodard's Flies Are Model Organisms for Genetic Research


PAUL SCHNAITTACHER

In Clapp Hall's "Fly Room," Craig Woodard, associate professor of biological sciences, uses fruit flies to study how steroid hormones control development.

"You don't want to drink too much coffee before doing this," says Craig Woodard. Peering into a microscope, the associate professor of biological sciences steadies a pair of jeweler's tweezers above a slide mount. He may be using the tools of a diamond setter, but Woodard's quarry today is in many ways more precious than glittering stones. "See that blob of fat?" says Woodard. "It's the innards of a fruit fly larva."
Woodard is studying how steroid hormones control development. When that phrase earns a blank look, the professor is quick to frame his research in lay terms: "Anyone who's been through puberty is intimately aware of this process." Steroid hormones direct the development of secondary sex characteristics in humans (for example, the growth of facial and underarm hair). "And," emphasizes Woodard, "they control metamorphosis in insects."

Woodard's laboratory on the third floor of Clapp Hall, dubbed the "Fly Room," buzzes with activity. On the first day of winter break students come and go, checking on their research projects or delivering last-minute holiday greetings. Divya Mathur '03 will board a flight home to Madras, India, in a few hours, but for now she huddles at a lab counter doing "fly maintenance." Mathur explains: "I'm putting my flies in new vials to keep the population going. I have to do this once every week because they multiply so fast." As Mathur transfers the insects and their larvae (more prosaically known as "flies" and "maggots") to their new homes, she gives them a fresh feast of yeast. "The yeast ferments and makes alcohol," Mathur explains, then adds with a smile: "You could say the alcohol aids in their mating."

Just the §FTZ-F1, Ma'am

Just as the steroid hormones testosterone and estrogen control the development of the human embryo, so the steroid hormone ecdysone controls the metamorphosis of the fruit fly by regulating the activity of genes. Produced in a gland and put into circulation, ecdysone acts through proteins called hormone receptors. When ecdysone is absent, these receptors "turn off" the activity within a specific gene. But when ecdysone is dumped into circulation and docks, space-station style, with its hormone receptor, the gene becomes active; tuned in and turned on, so to speak.

In the fruit fly, a gene called E93 is responsible for the "death" of the larval salivary gland, an event that must occur if the fly is to develop into a normal adult. Woodard's research has shown that at the beginning of the fly's twelve-hour metamorphosis period, ecdysone appears in high amounts, after which it drops to a low level. Then, at the end of the metamorphosis period, ecdysone jumps up to a high level once again. At the beginning of metamorphosis, that pulse of ecdysone doesn't tell the structure to die, and the salivary glands remain to do their job; at the end of metamorphosis, the same signal, a pulse of ecdysone, does tell the cells to die and the salivary glands disappear. How that happens is central to Woodard's research.

Woodard and his colleagues have discovered that in order for the E93 gene to turn on during that second pulse of ecdysone and do its work of destroying cells, a "competence factor" must be present. When this mediator, called §FTZ-F1, is absent, E93 will not be activated even when the animal's system is flooded with ecdysone. "To simplify," says Woodard, "ecdysone alone does not turn on E93: cells live; ecdysone plus the competence factor §FTZ-F1 turns on E93: cells die. Next question: Why isn't §FTZ-F1 hanging around during the first pulse of ecdysone? Woodard and his colleagues have shown that it is the very ebbing and flowing of the ecdysone level, the low-high-low pattern, that brings §FTZ-F1 into play.

"Basically, we've answered our central question in this one case," says Woodard. "That serves as a model case to begin to understand how these things are happening in other animals."

Why so much interest in the love life of Drosophila melanogaster, the common fruit fly? "We rely on the fly's mating behavior to do genetics," says Woodard. "We have to take males with a certain genetic makeup and mate them with females with a certain genetic makeup. So my students and I spend hours setting up crosses. Since a female fruit fly only wants to mate with one male, we have to get the females when they haven't mated yet." Woodard laughs and adds, "Basically, we spend a lot of time collecting virgins."

Research here in the Fly Room revolves around two central scientific mysteries. First, how is it that a single steroid hormone can bring about different responses at different times during development? Woodard offers, by way of example, the hormone testosterone. During the growth of a human fetus, testosterone controls the development of male sexual organs; then, years later during puberty, the same hormone directs an entirely different set of developmental responses, the onset of secondary sex characteristics.

The second question that drives Woodard's research is this: How can a single steroid hormone produce different responses in different parts of an animal? Woodard considers the fruit fly a prime example of this phenomenon, which makes the Drosophila metamorphosis an ideal system within which to explore this question. "You've got this animal," says Woodard, "that's got a larval body carrying the adult body around inside it. This one steroid hormone, ecdysone, at the exact same time, tells the larval body cells to die and the adult body parts to develop."

While flies undergo metamorphosis and humans undergo embryonic development, Woodard explains, the basic processes are very similar: cell division, cell movement, and changes in the shapes of cells. But cell growth is only one facet of the developmental process. Certain cells must die in order for an organism to continue its journey into adulthood. For example, a human embryo's hands are originally webbed—the fingers connected by skin. During the developmental process the cells of that webbing are destroyed by programmed cell death, "cellular suicide." A similar process takes place during the development of the fruit fly. Drosophila must get rid of the larval body in order to become a full-fledged adult. Studying how ecdysone accomplishes that is the crux of Woodard's research.

Woodard began his current study as a postdoctoral fellow at the University of Utah in 1992. But he began working with flies well before that, first as an undergraduate at Bates College and later as a graduate student at Yale University. "I've been working with flies," says Woodard with a grin, "since the mid-'80s."

Twenty years in the company of flies hasn't dampened Woodard's interest in other pursuits. When he isn't dissecting maggots, lecturing, or supervising his research assistants, Woodard might be found plunging down a mountain bike trail somewhere in the Holyoke Range. It's one of the passions the wiry, energetic 38-year-old has managed to keep burning in his life as a teacher, researcher, husband, and father of two young boys. "This is a great area to be a mountain biker," says Woodard, who rides with a group of enthusiasts from the College and local community. He lets out a big laugh at the mention of another of his alter egos: rock musician. Before the boys came along, "Woody" played harmonica and sang with his band, the G-Strings. These days, most of the professor's leisure time is spent hiking, biking, and skiing with his wife and kids, who share his love of outdoor sports.

Last spring, Woodard was awarded a National Science Foundation Research at Undergraduate Institutions (RUI) Program grant. The $350,000, three-year grant pays the salary of Woodard's full-time research associate, Tina Fortier '95, as well as for research equipment and supplies and Woodard's travel to professional conferences. "I couldn't do my research without it," says Woodard emphatically.

The professor also credits the ongoing yields of his laboratory to his students: "Mount Holyoke students are great. I've had such good fortune having excellent students to work in my lab. This is a really good place to go if you want to get research done at an undergraduate institution." Divya Mathur couldn't agree more. Working in Woodard's lab has been one of her favorite experiences at Mount Holyoke. Says Mathur, "Professor Woodard is so willing to listen and talk to you about any question—however strange and ridiculous. I owe him a lot for his wonderful guidance and encouragement and the absolutely splendid time I have doing research in his lab."

Like all of the Fly Room's student researchers, Mathur works alongside Woodard at the cutting edge of his ongoing efforts to parse the mystery of development. "How do genes control the cellular processes that are involved in development?" asks Woodard. "How do genes control the construction of an animal? From what we learn we can make inferences about how genes are controlling the development of a human. By studying a model organism like a fruit fly we're learning the rules."

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