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."
ounter
is3,932
|
