Before joining Clemson’s faculty in 1999, Stephen Foulger spent a stint working in the fiber optics industry. Years later, that background drew his interest to a developing field that uses implanted fibers to deliver light signals deep within the brain to trigger neural activity.

Called optogenetics, the experimental technique offers a way to change activity in targeted regions of the brain from outside the skull, using pulses of light delivered to light-sensitive proteins in the neurons. Researchers have tested the approach in animal models to try to restore activity in regions affected by neurodegenerative disease, for example, or to damp down errant neural firing in epilepsy. Foulger, the Gregg-Graniteville Endowed Chair and Professor of Materials Science and Engineering, marveled at the technique’s potential for exploring brain function or treating disease.

“These light-sensitive proteins open or close synapses,” he explains. “You can localize synaptic behavior in regions of the brain using these light-tunneling fibers and these proteins.”

But the need to implant the optical fibers directly into the brain is a major limitation of the technique’s broader use. Researchers must remove a small piece of skull and leave the fibers in place for the duration of an experiment.

With his expertise in designing optical materials, Foulger realized it should be possible to accomplish the task without fibers. He is now working to harness the potential of optogenetics for wider use by designing new light-producing materials that could make the approach noninvasive and bring it within reach for medical applications.

BRIDGING WORLDS

Although X-ray-sensitive particles exist for many industrial applications, developing radioluminescent materials compatible with living systems comes with a different set of challenges. Biological environments are wet, messy and unpredictable. Materials may behave differently in cells than in a chemistry lab, and differently in a whole animal than in a pile of cells. Or their function may change with long-term versus short-term use.

Creating something for use in a living body adds many extra constraints that the materials science world doesn’t always face.

“You don’t have a complete open palette of materials you’d like to use because of toxicity,” Foulger says. “A lot of the stuff that’s out there that’s radioluminescent is going to poison you, so we have a pretty tight constraint on what we can develop and put into a biological system. When we do simple toxicity tests with something new and we find that the cells don’t seem to respond negatively to it — to us, that can be a great day because it means we can keep going with the chemistry.”

For these considerations, Foulger has worked closely with McMahon and Weick. They quickly discovered that bridging disciplines also requires a bit of translation. “Initially, their definition of nontoxic and our definition of nontoxic were really different,” McMahon says, describing the need to keep neural cells not just alive but also healthy and unstressed. “It’s taken us some time to learn each other’s languages because our worlds are very different.”

With their combined expertise, they’ve progressed to early functional studies of the radioluminescent particles in rat brain slices — sections cut from a whole brain to retain some of the circuitry and function but in a preparation that can be studied in a lab dish.

The preliminary data are promising, McMahon says. The team has confirmed that neither the particles themselves nor X-rays at the needed dose hurt neural function. Now, she says, “we’re putting the particles from Dr. Foulger’s group on our brain slice, using X-rays and attempting to control circuits.”

For McMahon, it’s exciting to finally start seeing the nanomaterials and the physiology work together: “This is a project that we as neuroscientists would never do on our own, without Steve Foulger’s expertise. And he would never do this without our expertise.”