Duke University (Durham, NC) researchers have developed a method to activate genes with blue light (known as optogenetics) in any specific location or pattern in a lab dish by crossing a bacterium's viral defense system with a flower's response to sunlight.
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With the ability to use light to activate genes in specific locations, researchers can better study genes' functions, create complex systems for growing tissue, and perhaps realize wound healing technologies. The study was led by Charles Gersbach, assistant professor of biomedical engineering at Duke University.
"This technology should allow a scientist to pick any gene on any chromosome and turn it on or off with light, which has the potential to transform what can be done with genetic engineering," says Lauren Polstein, a Duke PhD student and lead author on the work. "The advantage of doing this with light is we can quickly and easily control when the gene gets turned on or off and the level to which it is activated by varying the light's intensity. We can also target where the gene gets turned on by shining the light in specific patterns; for example, by passing the light through a stencil."
The new technique targets specific genes using an emerging genetic engineering system called CRISPR/Cas9. Discovered as the system that bacteria use to identify viral invaders and slice up their DNA, the system was co-opted by researchers to precisely target specific genetic sequences.
The scientists then turned to another branch of the evolutionary tree to make the system light-activated. In many plants, two proteins lock together in the presence of light, allowing plants to sense the length of day which determines biological functions like flowering. By attaching the CRISPR/Cas9 system to one of these proteins and gene-activating proteins to the other, the team was able to turn several different genes on or off just by shining blue light on the cells.
"The light-sensitive interacting proteins exist independently in plants," explained Gersbach. "What we've done is attached the CRISPR and the activator to each of them. This builds on similar systems developed by us and others, but because we're now using CRISPR to target particular genes, it's easier, faster, and cheaper than other technologies."
Potential applications include control of the level of a gene's activity from its natural position in chromosomal DNA, which would allow more accurate interpretation of the gene's role, says Gersbach. The light-induced system, he says, could also provide more control over how stem cell cultures differentiate into various types of tissues. And by creating different patterns of gene expression, Gersbach hopes the system can be used in tissue engineering.
Full details of the work appear in the journal Nature Chemical Biology; for more information, please visit http://dx.doi.org/10.1038/nchembio.1753.
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