CASPER, Wyo. — Researchers at the University of Wyoming have demonstrated that near-infrared light can be used to “control a cellular process in a mammal’s brain.”
“Strange things at the University of Wyoming, as one hears molecular biologist Mark Gomelsky talk about head replacements as routine laboratory procedures,” UW said in a June 28 news release.
“A little more conversation, and things become much clearer: bioengineering a protein.”
The research involved bio-engineering a protein by transferring the head of one protein to the body of another, UW said.
“’We are basically taking the body of one light-sensitive protein and the head from another protein — adenylate cyclase — and putting them together to produce a functioning chimera, akin to a sphinx with a lion body and a human head,’” Gomelsky told UW.
“’That’s perhaps a crude analogy, but I like it. It illustrates the scope of the challenge. Enzymes are not readily amenable to such drastic manipulation.’”
Near-infrared light can be used to activate the enzyme which then disrupts how information moves through the brain. UW said the researches demonstrated this in mice.
UW said that adenylate cyclase is responsible for making a molecule found in almost all mammalian brains which control information transfer and is “related to long-term memory formation.”
That molecule is known as cAMP.
“The lab’s result is a long-held dream of engineering an enzyme that can make cAMP when irradiated with near-infrared light, because such light can be delivered with spatial precision and for a specific duration, Gomelsky says.”
The cAMP molecule controls multiple cellular processes and the bio-engineered enzyme can be used to do things like activating insulin production, stimulate fat burning and send electrical impulses to pacemaker cells in the heart, according to Gomelsky.
The research was conducted as a collaboration between UW’s College of Agriculture and Natural Resources and the Department of Zoology and Physiology.
“To test whether the engineered enzyme can be activated by external light in a live mammal, the lab turned to collaborator Professor Qian-Quan Sun in the Department of Zoology and Physiology, who studies mouse neurobiology,” UW said.
Gomelsky explained to UW how cAMP is involved in memory formation.
“The transfer of information from short-term to long-term memory shows up as electrical spikes, called spindle waves,” UW said. “Electric currents are initiated by specific ion channels and are transmitted through neurons from one brain region (thalamus) to another (cortex).”
“If a gene for the light-sensitive enzyme were delivered in the brain region where the spikes originate, the near-infrared light would stimulate the production of cAMP, which would open ion channels and disrupt the electrical circuit. That was the prediction.”
After placing a gene for the enzyme into a mouse brain in Sun’s laboratory, graduate students used a hand-held laser broadcast near-infrared light “to turn on the enzyme while the mouse was sleeping.”
Graduate student Chen Zhou observed a decrease in the spindle waves when the light was applied to the mouse’s brain, according to Gomelsky.
Having demonstrated the principle behind the work, more research is being conducted.
“‘We made a great tool but still fairly crude,’” Gomelsky told UW. “’We need to optimize it to ensure the head communicates well with the body of the protein.’”
In addition to working to improve the protein’s ability to interact with cAMP, “Gomelsky also works on modifying the protein to make another important signaling molecule in mammals, known as cGMP,” according to UW.
“‘It’s a one-letter change in the name but a big change in the protein,’ he says. ‘cGMP is not quite as omnipresent in cells as cAMP but is very important.’”
Reseachers elsewhere are also conducting work with the enzyme that was bio-engineered by UW researchers.
“Emmanuel Tzanakakis, a bioengineering professor at Tufts University, is testing the engineered enzyme in insulin-producing cells in mice,” UW said. “Gomelsky says collaborators in Germany are looking at whether the light-activated enzyme can be used to stimulate fat degradation.”
The research has been explained in greater detail.
“’Engineering Adenylate Cyclase Activated by Near-Infrared Window Light for Mammalian Optogenetic Applications‘ was published May 30 in the American Chemical Society’s journal ACS Synthetic Biology,” UW said.
“’It took us quite a while to find the proper ‘body parts,’ or protein modules, that are stable and active at mammalian temperatures,’ Gomelsky says. ‘This paper describes the success in finding those bacterial protein parts, and Anastasia Fomicheva, a Ph.D. student in my lab, made these parts work together.’”
