GLOW-IN-THE-DARK ZEBRAFISH AT UH HOLD
KEYS TO BIOLOGICAL CLOCKS
Professor Gregory M. Cahill’s Research Illuminates a ‘First’
in This Species
HOUSTON, Feb. 1, 2005 – Using genetically altered zebrafish
that glow in the dark, University of Houston researchers have found
new tools that shed light upon biological clock cycles.
Gregory M. Cahill, associate professor of biology and biochemistry
at UH, and Maki Kaneko, a fellow UH researcher who is now at the
University of California-San Diego, presented their findings in
a paper titled
“Light-dependent Development of Circadian Gene Expression
in Transgenic Zebrafish,” appearing Feb. 1 in the Public Library
of Science’s PLoS Biology, an online journal that, along with
PLoS Medical, is committed to making scientific and medical literature
a public resource.
“By injecting the luc gene that makes fireflies glow into
our zebrafish, our bottom-line finding goes back to nature versus
nurture,” Cahill said. “We found that these per3-luc
zebrafish contain something in their genetic makeup that gets their
clocks ticking without parental influence, however, we determined
that it does take some sort of environmental input for the clock
to start. In this case it was exposure to light/dark cycles after
the fourth day of development, about the age when the fish start
to swim and feed.”
The researchers used zebrafish (danio rerio) because they yield
such a high output of spawn, with hundreds of eggs being laid by
each female per week. This gives the scientists a better chance
of identifying mutant fish whose biological clocks run fast or slow,
providing the ability to trace the specific genes that create the
anomaly. Putting UH a bit ahead of other institutions engaged in
this type of research, Cahill and his team will be able to analyze
more than 2,000 zebrafish per week. The per3-luc zebrafish is the
first vertebrate system available for this level of high-throughput
measurement.
“Because we can test so many zebrafish at a time, the one
in a thousand odds of finding a mutant are more easily and efficiently
attainable,” Cahill said. “Ultimately, this type of
research can help with tracing why humans develop such things as
sleep disorders or mental illnesses like depression.”
Per3 is the naturally occurring clock-regulated gene. The protein
that it encodes is produced at highest levels near dawn, and when
the luc gene is inserted into it, the luciferase protein is produced
in a similar way. The result is that these fish glow rhythmically,
emitting more light during the day than during the night. The amount
of light is below the level of detection by the human eye, but it
is easily measured with an instrument called a luminometer.
“This has given us the tool we need to find other parts of
systems that influence biological clocks,” Cahill said. “We
are optimistic that this will shed light upon such things as reproduction
in other light-dependent animals.”
These findings have laid the groundwork for further study along
these lines. With a team now built, UH graduate students who assisted
with this project are now trained to work with Cahill to implement
the next steps of this research.
Prior to coming to UH in 1994, Cahill was a research assistant
professor in the Department of Anatomy and Cell biology at the University
of Kansas Medical Center in Kansas City and received his postdoctoral
training at Emory University. He received his doctorate in biology
and neuroscience from the University of Oregon in Eugene, where
he studied the mechanisms of circadian responses to light. He graduated
with his bachelor of science from the College of Biological Sciences
at the University of Minnesota in Minneapolis/St. Paul. His research
interests include molecular, cellular and physiological mechanisms
of vertebrate circadian rhythmicity, photoreceptor cell and molecular
biology, and neurobiology. He is a member of the Society for Research
on Biological Rhythms and the Society for Neuroscience and is currently
funded under a $1.2 million National Institutes of Health grant
through 2007 as the principal investigator on “Genetic analysis
of zebrafish circadian rhythmicity,” under which this latest
study falls.
UH’s Biological Clocks Program is one of the world’s
leading centers for circadian rhythms research, with five laboratories
and a team of more than 30 scholars. In addition to Cahill, the
group is led by four other tenured faculty members in the biology
and biochemistry department – Professor Stuart Dryer, Professor
Arnold Eskin, Professor Paul Hardin and Professor Michael Rea. For
more information on the biological clocks program at UH, visit http://www.bchs.uh.edu/research_clocks.htm.
PLoS Biology was first published in October 2003 and has been embraced
worldwide by scientists, as well as receiving international media
acclaim for the high-impact research it publishes. The PLoS is a
nonprofit organization of scientists and physicians dedicated to
opening doors to a worldwide library of the latest scientific research,
giving unlimited access to scientists, physicians, patients and
students, alike. The ultimate goal is to enable anyone with interest
to develop innovative ways to implement the world’s vast treasury
of scientific ideas and discoveries. For more information and a
copy of Cahill and Kaneko’s article, visit www.plos.org.
SOURCE: Cahill, 713-743-2694; gcahill@uh.edu
Web page: http://vnet.uh.edu/webpages/bio/homepage_bio.lasso?155622-961-5=gcahill#
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