Nav: Home

Engineers create most efficient red light-activated optogenetic switch for mammalian cells

March 13, 2018

A team of researchers has developed a light-activated switch that can turn genes on and off in mammalian cells. This is the most efficient so-called "optogenetic switch" activated by red and far-red light that has been successfully designed and tested in animal cells--and it doesn't require the addition of sensing molecules from outside the cells.

The light-activated genetic switch could be used to turn genes on and off in gene therapies; to turn off gene expression in future cancer therapies; and to help track and understand gene function in specific locations in the human body.

The team, led by bioengineers at the University of California San Diego, recently detailed their findings online in ACS Synthetic Biology.

"Being able to control genes deep in the body in a specific location and at a specific time, without adding external elements, is a goal our community has long sought," said Todd Coleman, a professor of bioengineering at the Jacobs School of Engineering at UC San Diego and one of the paper's corresponding authors. "We are controlling genes with the most desirable wavelengths of light."

The researchers' success in building the switch relied on two insights. First, animal cells don't have the machinery to supply electrons to make molecules that would be sensitive to red light. It's the equivalent of having a hair dryer and a power outlet from a foreign country, but no power cord and no power outlet adapter. So researchers led by UC San Diego postdoctoral researcher Phillip Kyriakakis went about building those.

For the power cord, they used bacterial and plant ferredoxin, an iron and sulfur protein that brings about electron transfer in a number of reactions. Ferredoxin exists under a different form in animal cells, which isn't compatible with its plant and bacteria cousin. So an enzyme called Ferredoxin-NADP reductase, or FNR, played the role of outlet adapter.

As a result, the animal cells could now transfer enough electrons from their energy supply to other enzymes that can produce the light-sensitive molecules needed for the light-activated switch.

The second insight was that the system to make light-sensitive molecules needed to be placed in the cell's mitochondria, the cell's energy factory. Combining these two insights, the researchers were able to build a plant system to control genes with red light inside animal cells.

Red light is a safe option to activate genetic switches because it easily passes through the human body. A simple way to demonstrate this is to put your hand over your smart phone's flashlight while it's on. Red light, but not the other colors, will shine through because the body doesn't absorb it. And because it's not absorbed, it can actually pass through tissues harmlessly and reach deep within the body to control genes.

Bioengineers built and programmed a small, compact tabletop device to activate the switch with red and far-red light. The tool allows researchers to control the duration that the light shines, down to the millisecond. It also allows them to target very specific locations. Researchers showed that the genes turned on by the switch remained active for several hours in several mammalian cell lines even after a short light pulse.

The team recently received an internal campus grant to use the method to control gene activation in specific regions of the brain. This would allow them to better understand gene function in a variety of neurological disorders.

The researchers patented the use of ferredoxins and FNR to target the enzymes needed to make light-activated molecules. The technology is available for licensing.

Importantly, insights about how to produce plant molecules in animal cells could also one day enable production of other molecules that can lead to the cultivation of plants that do not need fertilizer and make biofuel production more efficient.
-end-
The study was supported by the Kavli Institute for Brain and Mind at UC San Diego and the Salk Institute, the National Science Foundation, and the National Institutes of Health.

The research team included researchers from the Division of Biological Sciences, the Neurosciences Graduate Program and the School of Medicine at UC San Diego, as well as researchers at Quinnipiac University and the University of Iowa.

Biosynthesis of Orthogonal Molecules Using Ferredoxin and Ferredoxin- NADP+ Reductase Systems Enables Genetically Encoded PhyB Optogenetics

Phillip Kyriakakis, Marianne Catanho, Nicole Hoffner, Walter Thavarajah, Vincent Jian-Yu, Syh-Shiuan Chao, Athena Hsu, Vivian Pham, Ladan Naghavian, Lara E. Dozier, Gentry Patrick, and Todd Coleman

DOI: 10.1021/acssynbio.7b00413

University of California - San Diego

Related Molecules Articles:

The inner lives of molecules
Researchers from Canada, the UK and Germany have developed a new experimental technique to take 3-D images of molecules in action.
Novel technique helps ID elusive molecules
Stuart Lindsay, a researcher at Arizona State University's Biodesign Institute, has devised a clever means of identifying carbohydrate molecules quickly and accurately.
How solvent molecules cooperate in reactions
Molecules from the solvent environment that at first glance seem to be uninvolved can be essential for chemical reactions.
A new way to display the 3-D structure of molecules
Berkeley Lab and UC Berkeley Researchers have developed nanoscale display cases that enables new atomic-scale views of hard-to-study chemical and biological samples.
Bending hot molecules
Hot molecules are found in extreme environments such as the edges of fusion reactors.
At attention, molecules!
University of Iowa chemists have learned about a molecular assembly that may help create quicker, more responsive touch screens, among other applications.
Folding molecules into screw-shaped structures
An international research team describes the methods of winding up molecules into screw-shaped structures.
Artificial molecules
A new method allows scientists at ETH Zurich and IBM to fabricate artificial molecules out of different types of microspheres.
Molecules that may keep you young and alive
A new study may have uncovered the fountain of youth: plant extracts containing the six best groups of anti-aging molecules ever seen.
Fun with Lego (molecules)
A great childhood pleasure is playing with LegosĀ® and marveling at the variety of structures you can create from a small number of basic elements.

Related Molecules Reading:

Molecules: The Elements and the Architecture of Everything
by Theodore Gray (Author), Nick Mann (Photographer)

Reactions: An Illustrated Exploration of Elements, Molecules, and Change in the Universe
by Theodore Gray (Author)

DMT: The Spirit Molecule: A Doctor's Revolutionary Research into the Biology of Near-Death and Mystical Experiences
by Rick Strassman (Author)

Molecules Of Emotion: The Science Behind Mind-Body Medicine
by Candace B. Pert (Author)

Napoleon's Buttons: How 17 Molecules Changed History
by Penny Le Couteur (Author), Jay Burreson (Author)

We Are All Made of Molecules
by Susin Nielsen (Author)

Atoms and Molecules (My Science Library)
by Tracy Maurer (Author)

Taste Buds and Molecules: The Art and Science of Food, Wine, and Flavor
by Francois Chartier (Author)

The Billion Dollar Molecule: One Company's Quest for the Perfect Drug
by Barry Werth (Author)

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Circular
We're told if the economy is growing, and if we keep producing, that's a good thing. But at what cost? This hour, TED speakers explore circular systems that regenerate and re-use what we already have. Guests include economist Kate Raworth, environmental activist Tristram Stuart, landscape architect Kate Orff, entrepreneur David Katz, and graphic designer Jessi Arrington.
Now Playing: Science for the People

#504 The Art of Logic
How can mathematics help us have better arguments? This week we spend the hour with "The Art of Logic in an Illogical World" author, mathematician Eugenia Cheng, as she makes her case that the logic of mathematics can combine with emotional resonance to allow us to have better debates and arguments. Along the way we learn a lot about rigorous logic using arguments you're probably having every day, while also learning a lot about our own underlying beliefs and assumptions.