Lighting the way to
understanding cells,
network activities
and possible
future therapies.



Light already has a major role in medicine — specific wavelengths of light are used in various treatments and research efforts — but that role may be growing.

X-rays, which are invisible to the eye, can make the stuff inside us visible. Ultraviolet light can treat skin diseases such as psoriasis. And bright light boxes help stabilize the moods of patients with seasonal affective disorder.

Beyond these applications, investigators at the School of Medicine’s Department of Anesthesiology are using genetic engineering to influence how cells respond to light.

One team is investigating proteins in the eye called opsins, which allow photoreceptor cells to convert light into vision and enable us to see, to activate other types of cells. This allows the scientists to use light to control cell behavior.

Other investigators are working with optogenetics — using light to influence specific neurons in animals in order to map brain circuits and understand complex behaviors related to sleep, depression, anxiety and pain.

Potentially their findings could allow the development of precisely targeted light-based therapies.


The work of N. Gautam, PhD, and Ajith Karunarathne, PhD, activates opsin-expressing cells with a selected wavelength of light in an imaging laboratory.


Moving single cells

Opsins can do more than “see” in the way we typically think of seeing. In fact, they can activate cells to respond to their environments.

Light sources (rectangles) attract modified cells.

N. Gautam, PhD, professor of anesthesiology and genetics, and postdoctoral research associate Ajith Karunarathne, PhD, are exploring how light can cause opsins to behave in cells. When they inserted opsin proteins, which are G protein-coupled receptors (GPCRs), into cells, they found that by shining light on the cells, they could activate specific areas. This bit of genetic engineering permits opsins to activate other types of cells.

“Some of these opsins have properties that we thought might allow us to localize the signaling activity in a cell to a particular location in the cell,” says Gautam. “So we began experimenting, and we found that we could, in fact, localize the signaling to one side of the cell or another. A great deal of cell behavior results from signaling where the cell will sense something on its right, for example, and then move toward that substance, or move away from it.”


Opsin power

An immune cell, for instance, that receives a signal and senses a bacterial infection or inflammation, will travel in the direction of the bacteria or the inflammatory molecules. When Gautam and Karunarathne inserted opsins into immune cells, the cells moved toward a light beam.

“We can use light as a kind of ‘on-off’ switch to control cell behavior,” says Gautam. “Much of the way cells behave is due to their ability to sense signals in the environment. In our experiments, the cells sense the presence of light.”

In neurons, they have used light to coax the cells into growing new branches called neurites. They are planning similar things in heart cells and in pancreatic cells.

The goal with the heart cells would be to use light to slow down, or speed up, the rate at which the cells pulse. In pancreatic cells, they want to use light to get the cells to secrete insulin.

“We believe that with these techniques, it’s likely that any process that can be controlled by signaling from GPCRs can also be controlled by light,” Gautam says.

Although Gautam believes that inserting opsins into cells has immense therapeutic potential, he says it will be a while before the strategy is ready for clinical use. For one thing, it will require gene therapy in order to introduce the light-sensitive proteins into specific cell populations. For another, it will require a way to introduce light into cells deep inside the body, perhaps using micro-light emitting devices (LEDs).

While his laboratory is working on ideas to take this strategy from the culture dish into whole animals, they also are creating a library of several different opsin proteins capable of controlling cell behavior.

“As we move forward, one of our goals is to continue testing multiple opsins from different organisms to learn which ones work best,” he says.


Michael R. Bruchas, PhD, and Robert W. Gereau IV, PhD, are collaborating to demonstrate the ability of light-sensitive opsin proteins to control neuronal function using electrohysiological recordings of mouse brain neurons expressing these proteins.


Activating cells in a network


Light can influence neurons in animals that have been genetically engineered so that specific neurons will be activated and respond to light. Michael R. Bruchas, PhD, assistant professor of anesthesiology, and Robert W. Gereau IV, PhD, professor of anesthesiology and of neurobiology, are part of a group of scientists working in optogenetics.

Through their work with collaborator John A. Rogers, PhD, and engineers at the University of Illinois, they received a $3.9 million Transformative Research Project award supported by the National Institutes of Health


Networking cells

The researchers developed microscale, light-emitting devices (LEDs) — the first use of these devices in optogenetics — that allow them to map the properties of neural circuits involved in injury, pain, anxiety and other problems.

Bruchas was able to implant the devices in mice, prodding their neurons to release dopamine, a chemical associated with pleasure. Because the LEDs are wireless and tiny, they don’t interfere with normal behaviors. The mice move freely about their cages and can explore a maze or run on a wheel.

Bruchas and the investigators taught the mice to poke their noses through a specific hole in a maze. Each time, the system wirelessly activated the micro-LEDs, which emitted light, causing neurons to release dopamine.

“The micro-LEDs activated networks’ cells that are influenced by the things humans also find rewarding, like sex or chocolate,” says Bruchas. “When the cells were activated to release dopamine, the mice quickly learned to poke their noses through the hole even though they didn’t receive food as a reward.”

He says the devices should allow scientists to identify and map brain circuits involved in many complex behaviors. “Understanding which populations of neurons are involved in these complex behaviors may allow us to target specific brain cells that malfunction in depression, pain, addiction and other disorders,” Bruchas says.

In Gereau’s laboratory, the devices are implanted near peripheral nerves to interrupt or redirect pain signals. “Rather than identifying specific stimuli, we just want to turn off the cells causing pain,” says Gereau, who is director of the Washington University Pain Center.

But before those devices will relieve pain or stress, patients will need gene therapy that makes certain cells respond to light signals.

Gereau believes a common-sense strategy for doing so lies in a viral attack on the peripheral nervous system.

“If we can find a way to use a harmless version of the herpes simplex virus to deliver light-sensitive proteins to peripheral nerve cells, we believe we may be able to control the activity and signaling of those cells,” says Gereau. Bruchas, Gereau and colleagues hope that someday their work with micro-LEDs may illuminate ways of controlling behavioral disorders and pain in humans.