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Zebrafish are ideal subjects for studying genetic modification (Photo by Kristin Seward)
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Issac Skromne, associate professor at University of Richmond (Photo by Jamie Betts)
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Dr. Usua Oyarbide, a member of Dr. Corey's laboratory (Photo by Kristin Seward)
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Wilmer Amaya-Mejia, a member of Dr. Corey's laboratory, creates a presentation comparing zebrafish (Photo by Kristin Seward)
Zebrafish, Asian freshwater fish with zebra-like stripes, just might be life savers.
They’re natives to India, but they’re making a splash in medical research in two laboratories in Richmond: at Virginia Commonwealth University, where they are subjects in leukemia research, and at the University of Richmond, where they’re being used to test treatments for bone diseases.
Isaac Skromne, an associate professor in biology, is using the fish in his UR laboratory to test ways to administer medication directly to the bones through nanodots of carbon. The goal is to develop a treatment for osteoporosis that may bypass side effects such as nausea that are associated with current treatments. The work may even lead to ways to reverse the bone loss that occurs with the condition.
Zebrafish make great research subjects, and they have been in use since the 1970s. They’re cheaper to maintain than mice or rats; they develop faster, so researchers can complete generations’ worth of studies at a faster pace; and they share a majority of genes with humans. Also, their embryos are transparent and develop outside of the parent, so scientists can see how development occurs.
That’s an asset in Skromne’s work, which includes observing how a fertilized egg organizes its organs and tissues. He looks at the genes to see which part of the nervous system becomes the brain and which part becomes the spinal cord. In using a subject with a transparent embryo, he is able to physically see where and when the nervous system splits.
Chicken and mice also share a number of genes with humans and are good subjects for genetic research, but their embryos are not transparent as in zebrafish, which are ideal subjects for the study of genetic modification. Skromne says his researchers can see exactly what is being affected and how development changes based on the modifications they make to the fish genes.
“What’s exciting to me about working with zebrafish is their versatility,” he says. “One can use them to study almost everything: how a single cell develops into a full organism, how animals learn, addiction, cancer, etc.”
Part of Skromne’s research involves retinoic acid, a medication commonly used to treat acne. The acid is applied to the retinoic pathway, the gene thought to affect bone growth, with a goal of stimulating bone re-formation. “If it works, we can move to other signals, one at a time,” says Skromne.
The impact could be immense. Osteoporosis eventually affects 1 in 3 women and 20 percent of men. Available treatments stop the process but do nothing to replace tissue that has already been lost.
By applying carbon nanodots directly to problem areas on a bone to administer medication, areas that need bone tissue replacement can be treated without disrupting functions in the body elsewhere. That’s crucial, because stimulating the wrong cells could lead to such problems as triggering a cancer in the bone, Skromne says.
The project is a collaboration with Miami University, which is manufacturing the carbon nanodots and the medications. The work is funded through $343,881 in federal grants.
Skromne is also involving undergraduates in the research, allowing them to learn about the biology of zebrafish and the chemistry behind the components used in the project.
At VCU, scientists are using zebrafish to help find ways to prevent and treat blood cancers.
Seth Corey, professor and chief and Children’s Hospital Foundation Endowed Chair at the Children’s Hospital of Richmond at VCU, and his researchers are trying to develop a diagnostic test to identify people at risk for developing cancers such as bone marrow syndrome and other inherited disorders. He is using zebrafish to speed up the research process. It takes only four or five days for a zebrafish to develop its major organs while it takes a mouse 21, and it takes only four months to develop the first generation of genetically engineered zebrafish while it takes almost a year in mice. Having more zebrafish in the correct condition at one time gives researchers statistical power.
“They develop quickly,” says Corey. “They lay, like, 100 eggs at a time, so you can use statistics to pick up small differences easier.” And as an added bonus, he notes: “They are cute and don’t bite.”
Corey has been investigating myeloid leukemia and bone marrow failure syndromes for 20 years, but it is only in the past nine years that he has been using zebrafish. The pace of research has accelerated in the last four years because technology has improved, he says. “Sometimes you have to wait for the technologies to develop before you can answer the questions,” he says.
The VCU researchers are trying to induce leukemia in the fish by changing genes. Once they determine which genes are involved in the disease process, they hope to test drugs that mayprevent leukemia.
Corey says his team is much like meteorologists studying a hurricane. While weather-watchers assess data to see where a storm formed, where it will go next and how hard it will hit, his team uses zebra-fish to collect data to see where hereditary diseases and cancers originate, when and where they will occur, and how severe the impact will be. The goal is to understand how leukemia develops and what can be done to prevent it in children and adults.
“We need more knowledge quickly, and we want to translate that knowledge to better therapies for our patients,”Corey says.
