Optogenetics: Revolutionizing a revolutionary technology

Optogenetics, a technology that allows scientists to control cells with light, has blown the doors wide open in neuroscience since its debut less than a decade ago.

With a new $1-million grant from the W.M. Keck Foundation, a team of neuroscientists at Brown University and Central Michigan University will strive to make it even more powerful in the brain and beyond.

The revolution that optogenetics technology has brought to biology — neuroscience in particular — could be transformed all over again if a new project getting underway at Brown University and Central Michigan University (CMU) is successful.

First introduced in a practical form in 2005, optogenetics gave brain scientists the amazing new capability to use pulses of laser light to control almost any type of neuron in any area with precise timing. Prior means of controlling neurons weren’t ideal. Electrical pulses were powerful but drove all the cells in an area, not just desired cell types. Drugs couldn’t confine control to a particular area and didn’t have precise timing. Optogenetics could do it all by genetically engineering cells to become excited or suppressed by different colors of light.

But optogenetics can still do more, said Christopher Moore, associate professor of neuroscience at Brown, who leads the new project, funded by a new $1-million grant from the W.M. Keck Foundation. His goal is to make cells “smart” enough to emit light precisely when needed in order to optogenetically control themselves or their neighbors. If optogenetics is ever approved for human use, this new form of self-regulation — which would not involve injecting light into the body from outside — could produce new ways to treat problems ranging from epileptic seizures to Parkinson’s disease to diabetes.

‘BL-OG,’ and beyond

In 2013, Moore’s collaborator Ute Hochgeschwender, associate professor at CMU, demonstrated how to make optogenetic cells emit their own light using a capability widely found in nature: bioluminescence. Bioluminescence is the natural chemical reaction that allows fireflies and many sea creatures to make light. The advance of pairing bioluminescence with optogenetics allowed scientists to make the technology wireless. In most optogenetic experiments, laser light is delivered into the body by a fiber optic cable, but with BL-OG — shorthand for BioLuminescent-OptoGeneticsBioLuminescent-OptoGenetics — a cool, biologically compatible light could be triggered in cells just by administering a drug.

Now the team of Moore, Hochgeschwender, and Brown professors Barry Connors, Julie Kauer and Diane Lipscombe, interim director of the Brown Institute for Brain Science, will pursue the next big step.

“In the new grant, what we’re doing is taking BL-OG and bringing it to where it starts to get transformatively different from anything else that’s existed,” Moore said.

The idea is to program BL-OG cells to emit their light when they sense a need. As living entities, cells spend their lifetimes sensing their environment and carrying out genetic instructions to implement complex activities, such as expressing proteins, generating energy, or even countering threats. Why not try to combine that programmability with BL-OG to help cells help each other or themselves?

“Right now I could give a pill that makes cells glow and it would have an effect for a period of time,” Moore said. “What would be really neat is if we could regulate a circuit only when it’s behaving badly. What you’d love to do is let the cell have its normal pattern of activity, and then intercede at that [problematic] moment. It’s a real-time feedback approach.”

Epilepsy, for example

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