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Shining new light on gene expression
CAMBRIDGE, Mass.—Innovative new technology developed by researchers from Harvard University and MIT working at the Broad Institute in Cambridge, Mass., can rapidly start or stop the expression of any targeted gene simply by shining light on the cells. Employing a technique called optogenetics that uses proteins that change function in the presence of light, the team of researchers adapted light-sensitive proteins to stimulate or suppress the expression of a specific gene in response to light.
In this study, the researchers tried targeting nearly 30 genes in neurons grown in the lab and in living animals. Using this technique, gene expression could be stimulated or suppressed almost immediately. The light-sensitive proteins could be targeted to precisely alter a specific epigenetic marker at a specific location. This ability to precisely control timing and duration of gene expression is vastly superior to existing methods of perturbing gene expression.
Professor of bioengineering at Stanford University and one of the inventors of optogenetics, Dr. Karl Deisseroth, says the most important innovation seen in this new technique is its ability to control of genes that occur naturally within the cell, rather than relying on manipulating engineered genes delivered by scientists. Deisseroth was not part of the research team.
The implications of this new technology are many, but the most immediate applications may be in research focused on learning and memory. The technology should allow researchers to use a beam of light to activate and deactivate certain processes in animal or human brain cells to see how genes are involved in the process of learning and memory formation.
Another promising area of application may be using this technique to study epigenetic changes in cells more broadly. Using the technology in conjunction with histone or DNA modification can allow researchers to precisely alter an epigenetic marker, giving robust insights into that marker's function.
"This could allow you to go into the cell and make changes at a specific location to see what the epigenetic marker is doing," says Dr. Feng Zhang, a core member of the Broad Institute and MIT's McGovern Institute for Brain Research.
The next steps for further research into this emerging technology focus on expanding the level of control of gene expression. So far, the technique only uses blue light, but the researchers hope to be able to use other colors of light in the future.
The researchers are now trying to expand the types of histone modifiers they can incorporate into the system.
"It would be really useful to expand the number of epigenetic marks that we can control," said Mark Brigham, a graduate student at the Harvard School of Engineering and Applied Sciences, in a media release about the research's impending publication. "At the moment, we have a successful set of histone modifications, but there are a good deal more of them that we and others are going to want to be able to use this technology for."
"We want to be able to change more and different histone markers," says Zhang. "We also want to begin to apply this technique to studying learning, memory and brain function."
Brigham and Silvana Konermann, a graduate student at MIT, are co-lead authors of the paper published in Nature describing the technique. Zhang, an assistant professor of neuroscience and biological engineering at MIT, had worked with Deisseroth to develop optogenetics in 2010. This latest research was among the first projects on which he and the co-authoring graduate students began collaborating together in the lab.
The research was funded by a Hubert Schoemaker Fellowship; a U.S. National Institutes of Health (NIH) Transformative R01 Award; an NIH Director's Pioneer Award; the Keck, McKnight, Vallee, Damon Runyon, Searle Scholars, Klingenstein and Simons foundations; and Bob Metcalfe and Jane Pauley.