
AMES, Iowa – The tropical freshwater zebrafish (Danio rerio) is widely used as a model biological system for researchers studying human health. Like humans, zebrafish are vertebrates with similar organ systems for respiration and reproduction. Surprisingly, the species shares about 70% of its genome with humans. It also produces large numbers of transparent embryos that mature quickly, which makes the results of genetic manipulation relatively easy to see. Even with these advantages, scientists still lack specialized genetic tools to make full use of this powerful animal model for health studies.

A research team led by two Iowa State University geneticists has made significant progress to address this challenge over the past decade. The National Institutes of Health just recognized their leadership with support of almost $4 million over four years, allowing them to refine tools they originated and continue to train and support other researchers and students in use of the technologies.
Maura McGrail, a professor of genetics, development and cell biology, leads the new NIH project, working with her long-time partner in the lab and in life, Jeffrey Essner, a professor in the same department. The scientific duo have developed a state-of-the-art zebrafish discovery platform to research the genetics of health and disease.
With this new funding, they plan to build on their past work to better understand enzymes inside cells that help regulate the function of the genome, sometimes over generations. Another focus will be to explore metabolic disease biology, especially disorders of mitochondria, tiny organelles within cells where many of the processes of respiration and energy production take place. Problems with genome regulation and mitochondria can lead to a number of diseases in humans and other animals.
“Our overall goal is to continue to advance zebrafish as a model for human health research by opening new areas of investigation related to genetic development and disease,” McGrail said. “This research is widely applicable to other model systems, including humans, other animals and even plants.”
For this project, they are partnering with Iddo Friedberg, associate professor in the Department of Veterinary Microbiology and Preventive Medicine at Iowa State. Friedberg is a computational biologist who will help develop software to insert their experimental gene sequences in just the right places. Other partners on the new NIH project include Stephen C. Ekker at the University of Texas at Austin and Karl J. Clark at Texas A&M University.
This project builds on McGrail and Essner’s previous decade of NIH funding and seven collaborative publications on the development of CRISPR (clustered regularly interspaced short palindromic repeats) for genome engineering. Recent advances in CRISPR-engineered genes from McGrail’s lab are the driving innovations of the new grant’s proposed research. The modified genes have an element inserted into their DNA that allows precise control of when and where a mutation is introduced in an animal. With this critical advance, genes can now be studied in specific tissues and organs, to better understand how they contribute to human disease.
Funding for the zebrafish facility at Iowa State was largely supported by the Roy J. Carver Charitable Trust.
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Contacts:
Maura McGrail, Department of Genetics, Development and Cell Biology, 515-294-4445, mmcgrail@iastate.edu
Jeffrey Essner, Department of Genetics, Development and Cell Biology, 515-294-7133, jessner@iastate.edu
Iddo Friedberg, Department of Veterinary Microbiology and Preventive Medicine, 515-294-5959, idoerg@iastate.edu
Ann Y. Robinson, Agriculture and Life Sciences Communications, 515-294-3066, ayr@iastate.edu