Researchers Create Chemical 'Light Switches' to Aid Study of Gene Function (8/9/2007)

Zebrafish

Researchers at North Carolina State University have received a five-year, $1.4 million grant from the National Institutes of Health (NIH) to develop a series of "photo-switchable" compounds that will allow scientists to turn individual genes on and off within zebrafish embryos, enabling them to determine the function of particular genes.

Dr. Alex Deiters, assistant professor of chemistry in the College of Physical and Mathematical Sciences, and Dr. Jeff Yoder, assistant professor of molecular and biomedical sciences in the College of Veterinary Medicine, are the lead researchers on the project.

Zebrafish have long been used as a model for studying the functions of genes during embryonic development, due in part to the fact that the transparency of the zebrafish embryos makes observation much easier. The recent sequencing of the human and zebrafish genomes and identification of more than 30,000 genes have increased the zebrafish's importance as a model organism in helping to resolve the function of these individual genes.

"Traditionally, scientists have tried to figure out a gene's function by either over-expressing or genetically disrupting a particular gene and looking at what happens to the embryo as a result," Yoder says. "Does the embryo's heart or circulatory function change? Does it mimic a disease?"

The problem with this approach is that it lacks a mechanism for "spatio-temporal" control of the gene's expression. In living animals, genes are activated at particular times within an organism, and then switched off after they serve their purpose.

"To determine what the genes do, you must mimic nature's precision in turning genes on and off," Deiters says.

In order to address this problem, Deiters and Yoder have come up with a novel solution - the construction of photo-sensitive organic compounds that can bind to a specific RNA molecule and are responsible for "telling" the RNA, or expressed gene, when to switch off and on. These artificial gene switches are then introduced into zebrafish embryos and exposed to ultraviolet light, creating a literal "light switch" for genes.

Deiters and Yoder hope to create an entire array of these photo-sensitive compounds that are tailored to different types of RNA, in effect providing a suite of tools for the spatio-temporal control of gene expression in zebrafish.

"One of the major advantages of this approach is that it will allow scientists to switch off a gene that has previously been activated," Deiters says, "which currently is not possible. In addition, scientists can direct the light to individual cells, and that will enable them to see exactly what the gene in question is doing within the organism."

Note: This story has been adapted from a news release issued by North Carolina State University

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