Light switch added to gene tool opens new view of cell development

April 4, 2012
University of Oregon biologist Phil Washbourne collaborated with an Oregon company to develop a UV light-activated on-off switch for the vital gene-blocking molecule, an accomplishment that may help researchers around the world who are studying early developmental processes. Credit: University of Oregon

University of Oregon scientists collaborating with an Oregon company that synthesizes antisense Morpholinos for genetic research have developed a UV light-activated on-off switch for the vital gene-blocking molecule. Based on initial testing in zebra-fish embryos, the enhanced molecule promises to deliver new insights for developmental biologists and brain researchers.

The seven-member team describes the advancement in an open-access paper published in the May issue of the journal Development. UO neuroscientist Philip Washbourne, a professor of biology, says the paper is a "proof-of-concept" on an idea he began discussing with scientists at Gene Tools LLC in Philomath, Ore., about four years ago. Gene Tools was founded in the 1980s by James Summerton, who first invented Morpholino oligos. The company holds the exclusive license to distribute these molecules to researchers around the world.

Morpholinos are short-chain, artificially produced oligomers that bind to RNA in cells and block . For a decade, biologists have used them in , mice and African clawed toads to study development, but they remained in the active, or on, position. Gene Tools created and introduced a light-sensitive linker, allowing researchers to control the molecule -- even leaving one on in one cell and off in an adjacent cell -- with a pinpoint beam.

Researchers in Washbourne's lab -- led by associate Alexandra Tallafuss -- were challenged to give the new molecules a test run. They applied them to their work in zebra fish. "Now we can turn them on and off," Washbourne said. "You can insert them and then manipulate them to learn just when a gene is important, and we learned two things right away."

Researchers have known that if a gene known as "no tail" is blocked in development, zebra fish fail to grow tails. They now know that the no-tail gene does not need to produce protein for tail formation until about 10 hours, or very late, into an embryo's development.

Secondly, the researchers looked at the gene sox10, which is vital in the formation of neural crest cells, which give rise to dorsal root ganglion cells -- neurons that migrate out of the spinal cord -- and pigment cells. "Again, we found that sox10 is not needed as early in development as theorized," Washbourne said.

"These light-sensitive molecules significantly expand the power and precision of molecular genetic studies in zebrafish," said Robert Riddle, a program director at the National Institute of Neurological Disorders and Stroke (NINDS). "Researchers from many fields will be able to use these tools to explore the function of different genes in embryonic regions, specific cell types and at precise times in an animal's lifespan."

The NINDS and National Institute of Child Health and Human Development, both at the National Institutes of Health, supported the research through grants to Washbourne and Eisen.

"This successful collaboration between our scientists and this Oregon-based company shows that commercial innovation can come quickly by jointly addressing common needs," said Kimberly Andrews Espy, vice president for research and innovation at the UO. "This is a remarkable example of turning a concept into a working tool that likely will benefit many researchers around the world."

Related Stories

Recommended for you

A math concept from the engineering world points to a way of making massive transcriptome studies more efficient

November 17, 2017
To most people, data compression refers to shrinking existing data—say from a song or picture's raw digital recording—by removing some data, but not so much as to render it unrecognizable (think MP3 or JPEG files). Now, ...

US scientists try first gene editing in the body

November 15, 2017
Scientists for the first time have tried editing a gene inside the body in a bold attempt to permanently change a person's DNA to try to cure a disease.

Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)

November 15, 2017
The first genetic mutation that appears to protect against multiple aspects of biological aging in humans has been discovered in an extended family of Old Order Amish living in the vicinity of Berne, Indiana, report Northwestern ...

Genetic variant prompts cells to store fat, fueling obesity

November 13, 2017
Obesity is often attributed to a simple equation: People are eating too much and exercising too little. But evidence is growing that at least some of the weight gain that plagues modern humans is predetermined. New research ...

Discovering a protein's role in gene expression

November 10, 2017
Northwestern Medicine scientists have discovered that a protein called BRWD2/PHIP binds to histone lysine 4 (H3K4) methylation—a key molecular event that influences gene expression—and demonstrated that it does so via ...

Twin study finds genetics affects where children look, shaping mental development

November 9, 2017
A new study co-led by Indiana University that tracked the eye movement of twins finds that genetics plays a strong role in how people attend to their environment.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.