Some "fishy" research — in a potentially lifesaving way — is planned for the University of Utah starting next year.
U. medical researchers have been awarded an $8.2 million grant to study congenital heart defects, which are the top killer for children under the age of 1.
The U. "Zebrafish center" will be one of four U.S. facilities that will be established to study the disorder.
By using zebrafish — a 1-inch-long tropical minnow — in their studies, Utah researchers can gain a genome-wide perspective of the developing heart, which will be a first, according to Joseph Yost, Ph.D., professor of neurobiology and anatomy andpediatrics at the U.
"Researchers have studied heart development one gene at a time, and that has given us a lot of progress," Yost said. "But it's time to look at the whole genome of the developing heart. Through our zebrafish center, we will be able to look at every decision point of every gene during the process of building a functioning heart."
According to the March of Dimes, congenital heart defects are the No. 1 birth defect in the U.S., affecting more than 25,000 American babies born each year — including more than 300 babies born annually in Utah.
The research is part of a $100 million effort by the National Institutes of Health, called the "Bench to Bassinet program," which also establishes consortiums of human genomics and clinical centers. The six-year grant is issued through the National Heart, Lung, and Blood Institute.
"It recognizes the University of Utah as a premier institute for doing pediatric heart research," Yost said.
He also credited the support of the Primary Children's Medical Center Foundation, which contributed seed money several years ago to get the project rolling and make sure it was feasible before applying for the grant.
The three other centers to be opened will be at Harvard University, the University of Pittsburgh and The University of California, San Francisco — all of which will use mouse models for their studies.
The zebrafish make an excellent model for studying human biology for a variety of reasons, Yost says. Their genome is very similar to that of humans; they are prolific breeders, with short gestation periods, and females can produce 200 offspring a week, allowing researchers to examine thousands of related fish at different stages of heart development at the same time. The fish are also transparent during development, making it possible to actually see organ formation and function. And at only 1-inch-long, researchers can easily keep 20 zebrafish — a whole family — in a two-liter tank.
Researchers say that while the fish heart is relatively simple, it does most of what human hearts do.
Yost plans to study both the normally and abnormally developing heart at distinct stages in development. He and his team will introduce 100 or more gene mutations to observe how they influence the networks that regulate the 22,000 genes involved in zebrafish heart development. He also plans to look at how mutations affect various aspects of heart physiology, such as the electrical current that controls the heart beat.
This multilayered molecular profiling of heart development has not been performed in any organism to date, according to Yost.
"The kinds of things we are doing in zebrafish, can't be done in other model systems," he said. "We can ask what's happening with every gene in the developing heart."
Yost's co-investigators on the project are Bradley R. Cairns, Ph.D., professor of oncological sciences and an investigator with the U.'s Huntsman Cancer Institute, and Dr. Martin Tristani-Firouzi, a pediatric cardiologist and associate professor of pediatrics.
Cairns will lead a bioinformatics effort to use computer-based analyses of genome-wide data. Tristani-Firouzi will spearhead the part of the study that looks at heart physiology. By comparing normal and aberrant developing hearts, the researchers expect to uncover the molecular signatures of heart defects.
Although it's hard to predict what breakthroughs may come from the research, Yost believes it will result in findings that aid patients.
"We want to understand how the whole genome works as a network to build a properly functioning heart," he said, "and then use that knowledge to find ways to treat and cure children with congenital heart defects. There certainly will be some new insights into how to treat kids."
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