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Scientific
research crucial to UNT's vision of the future
The
ability
of a human embryo to survive and thrive depends in large measure on healthy
heart development. Many researchers suspect that heart defects in the
early stages of human development may be a major cause of fetal deaths.
Biologist Warren Burggren, Ph.D.,
dean of the College of Arts and Sciences at the University of North Texas,
is on a quest to learn more about how the heart develops before birth.
By studying animal embryos with hearts similar to those of humans before
birth, he hopes ultimately to help correct human heart defects.
"I decided to pursue prenatal cardiac research because
of my interest in the beginnings of life," says Burggren.
"The fact that a fragile egg, housing an embryo, will
grow into a fully developed animal fascinates me," he adds.
A
common thread
With
funding from the National Science Foundation, Burggren seeks to understand
and find ways to discourage anomalies that would prevent a fetus from
growing into a fully developed, healthy human being.
He uses the scientific approach created by the 19th-century
Danish animal physiologist August Krogh, who assumed that there is a specific
animal most suited to determine an answer to every human physiological
problem. Simply put, the observation of animals reveals valuable information
about human anatomy and physiology.
According to Burggren, life is like a colorful quilt.
Fish, reptiles and mammals are conceived from the same thread, but fetal
development eventually weaves humans and animals in different directions.
"It's this thread, running through our lives, that's
similar to the rest of the animal kingdom that intrigues me," says Burggren.
Emerging
life
Burggren
envisions an embryo as life waiting to burst forth and develop, "like
a rocket being propelled from a launch pad." He notes that any number
of things may happen to the rocket. It may function well and reach its
destination, or it may malfunction and change course. Understanding why
"course changes" occur in developing fetuses and how corrections are made
may ultimately reduce infant mortality.
Burggren says many variables may alter the way a heart
develops. These include environmental factors, such as oxygen and acidity
levels and temperature. In addition, he says maternal experiences —
such as the quality of nutrition or the amount of exposure to toxins,
alcohol and other chemical substances —
may have an effect. Studies show that genetic factors also play a part.
To learn how the fetal heart operates, Burggren conducts
his research in three laboratories —
an aquarium room, an incubation room and an experimental lab area. Each
has a distinct function.
Fish
exercise
The
40 aquariums lining the walls of the aquarium room serve as a gymnasium
of sorts for zebra fish. The hearts of these fish are similar to the human
heart in an early stage of development.
"These fish are actually trained to exercise by swimming against currents
of various speeds during their development," says Brian Bagatto, Ph.D.,
who just completed his degree in biology at UNT.
"Looking at the cardiovascular systems of active and
non-active fish, we noted hearts became more efficient at pumping blood
in active fish," says Bagatto. "This is because exercise causes lowered
oxygen levels in the growing fish."
UNT researchers will attempt to discover why lowered
oxygen levels in developing fish produce healthier hearts, while lowered
oxygen rates in developing human babies seem to have detrimental effects.
Bagatto notes that a human fetus has a lowered oxygen level when the mother
smokes.
Although the researchers will conduct more aquatic
studies about low oxygen levels in embryonic hearts, they have already
formed important conclusions about heart development.
For example, they determined there is a "critical window"
in development when swimming exercise is most effective in changing a
growing heart. Therefore, they conclude exercise before or after this
"critical window" has little effect.
Knowing at what point in development these critical
windows occur can provide insight into how environmental factors may influence
human fetal development.
On
camera
Like the hearts of the zebra fish, hearts in the eggs
of emus, chickens, quail and snakes are very similar to human hearts in
their early stages of development. All these types of eggs are nurtured
at one time or another in the incubation room.
Burggren selects the emu eggs for their large size
and ease of examination. Snake eggs are chosen because they can absorb
moisture in dry regions. They may provide valuable information about how
life develops with low water reserves.
More information about hearts is collected in the experimental room of
Burggren's lab. Like a television studio, it is wired for lights, camera
and action. In this room, Burggren and his colleagues can view individual
red blood cells in an animal as small as a larval fish or as large as
an emu embryo.
Equipped with the latest in computer imaging, this
lab room includes a bank of microscopes that serve different purposes.
An inverted microscope allows a specimen to be viewed from underneath.
Another microscope is attached to a light-sensitive camera and a computer.
The device enables UNT scientists to view an embryonic fish's entire cardiovascular
system at one time. Photographs trace the paths of its tiny red blood
cells.
Burggren can videotape the beating heart of an intact,
undisturbed fish embryo through a transparent egg to calculate the amount
of blood squeezed out of the heart with each beat. He illuminates a translucent
egg, which exposes blood circulating through veins. He can then determine
the amount of oxygen in the blood by looking at the intensity of color
— a bright red
indicates more oxygen than a dull red.
With a different bank of instruments, researchers can
view the developing hearts in larger animal eggs. Burggren can measure
blood flow in an emu egg, which weighs nearly one and one-half pounds.
"Actually, in many ways emu embryos are just like chick
embryos and just like zebra fish embryos early in development," says Burggren.
"We use them, in part, because they are large."
Large embryos are better suited for some experiments
because their entire, intact cardiovascular systems are easier to observe.
Other experiments focus on smaller embryos because they fit more easily
under a microscope.
In this way, says Burggren, researchers put together
that colorful quilt woven from the threads of many animals.
From
the heart of Texas
In
1999, UNT initiated the formation of the Environmental
and Genetic Growth Sciences (EGGS), a global collaboration of physiologists
interested in heart development.
The importance of this cooperative effort is reflected
by major international support of grants funded by the U.S. National Science
Foundation, UNT, the state of Texas, Austria, Germany, Britain, Japan,
Israel and Chile.
EGGS conducts global research designed to investigate
the cardiovascular growth of developing animals. The collaboration also
seeks to understand how genetics and environment shape the developing
heart.
EGGS researchers have concluded that genes and environment
interact in ways that were far more complex than first theorized. This
has led them to rethink the simple "nature vs. nurture" view of development.
Although his research influences global science, Burggren's
contribution to science and education starts at home in Texas. His lab
is a classroom for post-doctoral, graduate and undergraduate students
from the United States and such countries as Japan, Canada, Germany and
Austria. Their studies in heart development prepare them for careers in
basic research, applied health sciences and medicine.
The
future
"At
no time in its history has the study of the development of vertebrate
organisms been at a more exciting juncture," says Burggren.
"Researchers in this area are now employing new microscopic
tools and blending computer hardware and software in fantastic new ways."
He notes that our understanding about how animals develop is leaping to
a new level.
"International commitment, talented students, new tools
and experimental models along with funding are allowing us to learn more
at a faster rate," he says.
As the leader of the EGGS project, Texas is making
a major contribution to this field of study.
"The state of Texas can be proud of her students, professors
and researchers, because they are dedicated to studies that may one day
save human lives," Burggren says.
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