How algae helped reveal the power of light-sensitive proteins

Peter Hegemann of Humboldt University of Berlin and Georg Nagel of the University of Würzburg wanted to understand how tiny, single-celled algae detect light. Chlamydomonas can sense light even though it has no eyes, helping it respond to changes in its surroundings.

Light sensing is not limited to animals. Organisms throughout the living world use light to detect their environment, move toward or away from it, generate energy, and respond to changing conditions. Even single-celled organisms contain proteins that respond to light.

Hegemann and Nagel discovered that Chlamydomonas uses an ingenious light-detection mechanism based on a protein called channelrhodopsin.

Channelrhodopsin is embedded in the outer membrane of algal cells. Some parts of the protein face the water outside the cell, while others face the inside. The protein also contains a small molecule called retinaldehyde, which can absorb light.

When light strikes the retinaldehyde in channelrhodopsin, the molecule changes shape. This causes the channelrhodopsin protein to change shape as well, opening a small passage through the cell membrane.

Positively charged particles, including sodium ions, can then flow into the cell from the surrounding water. The movement of these charged particles sends a signal through the alga and helps it swim.

Why channelrhodopsin matters for neuroscience

The discovery became especially important because nerve cells also use the movement of charged particles, known as ions, across their membranes to control their activity. When positively charged particles flow into neurons, the cells become more active.

Researchers realized that if they could introduce channelrhodopsin into nerve cells, they might be able to activate those cells simply by shining light on them. That is what Hegemann, Nagel, and Karl Deisseroth, a psychiatrist and bioengineer at Stanford University in California, helped make possible.

Optogenetics: Turning nerve cells on and off with light

The ability to control nerve cells with light is called optogenetics. It has become a powerful research tool because scientists can use it to activate or inhibit specific groups of nerve cells and observe the results.

First, researchers deliver the channelrhodopsin gene to the nerve cells they want to study. The gene is usually carried into the cells by a modified virus that does not cause disease. The cells then produce channelrhodopsin, making them responsive to light.

In animals such as mice, scientists can shine light into the brain through thin optical fibers. When the light reaches a cell containing channelrhodopsin, the protein opens and the cell becomes active. Nearby nerve cells without the protein are not affected.

Because the light can be focused on very small areas of the brain and switched on or off quickly, optogenetics gives researchers precise control over neural activity. Scientists can use it to investigate whether particular groups of nerve cells are involved in memory, sleep, sensation, or movement.

Using light to reactivate memories in mice

In an 2012 experiment, a team from the Massachusetts Institute of Technology gave mice mild electric shocks inside a specific cage. Using optogenetics, the researchers tagged neurons in the brain’s memory center that were active during the fear-conditioning experiments.

Several days later, the scientists used light to activate those cells while the mice were in a different cage. The mice froze in fear, as if they were remembering the electric shock.

Mice that had not received shocks did not freeze, suggesting that the light was reactivating a specific memory. Deisseroth was one of the study’s authors.

Could optogenetics become a medical treatment?

Optogenetics has transformed scientists’ ability to study the brain and nervous system. It may also have potential as a future treatment. The technique has already entered early-stage clinical trials for people with retinal degeneration.

In these trials, researchers introduce light-sensitive proteins into nerve cells that remain in the retina after the cells that normally detect light—called rods and cones—have been lost. The surviving cells can then respond to light, potentially restoring some vision.

Researchers are also investigating whether optogenetics could eventually help treat neurological conditions such as Parkinson’s disease and epilepsy.

Why this Nobel Prize research matters

This year’s Nobel Prize celebrates research that began with a deceptively simple question: How does Chlamydomonas know which way to swim when it detects light?

The question did not initially appear to have an obvious practical use. It was not focused on an urgent human-health problem or a clear path to commercial success. Yet the discovery of channelrhodopsin ultimately led to optogenetics, one of the most precise methods scientists have for studying the brain.

The success of optogenetics highlights the importance of asking questions simply to understand the world. It is often impossible to predict where basic scientific knowledge will lead.