Genetically Engineered Protein Could Improve Optogenetics

By Joel Lindsey

Researchers at MIT have created a new light-sensitive protein that could make it possible to noninvasively control brain neurons using a light source located outside the skull.

The development could represent a potentially significant advancement in the field of optogenetics, which uses light to manipulate and control neurons in order to both study brain functions and treat a variety of brain-related health issues.

According to a press release published recently on MIT’s website, optogenetics requires the use of light-sensitive proteins called opsins, which have traditionally been produced by genetically modifying neurons. The opsins are then activated by using an implanted light source, such as an optical fiber. This approach can be problematic, however, since there are many instances in which inserting optical fibers into the brain is not feasible.

To overcome this problem, the MIT team focused on finding naturally occurring opsins that might react to red light, which can penetrate deeper than blue or green light — removing the need to implant a light source.

First, the researchers identified the presence of opsins in the bacteria Haloarcula marismortui, Haloarcula vallismortis. Then, by performing a series of genetic manipulations on some of these bacteria, researchers developed a protein that was highly sensitive to red light and that induced a strong enough electrical current to shut down neural activity.

“This exemplifies how the genomic diversity of the natural world can yield powerful reagents that can be of use in biology and neuroscience,” said Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT.

In early tests, Boyden and his colleagues planted the new protein, dubbed Jaws, inside the brain of a mouse. They were able to successfully activate the protein using an external light source. Upon activiation, the protein then induced a large enough electrical current to effectively shut off nearby neurons.

Researchers reported successful neuronal suppression using the Jaws protein when it was embedded at depths of up to three millimeters in the mouse’s brain.

While they have yet to use Jaws on larger animals or humans, researchers are hopeful that the newly designed protein could one day translate into effective and noninvasive treatments for a variety of brain-related disorders such as epilepsy. It could also help provide an effective form of treatment for retinitis pigmentosa, according to the press release.

“Since these molecules come from species other than humans, many studies must be done to evaluate their safety and efficacy in the context of treatment,” said Boyden.