A novel protein found in the coldest environments on Earth, such as Greenland’s glaciers and the peaks of Tibet, may hold the key to developing innovative new brain technologies, according to new research.
The recent work of Kirill Kovalev, a structural biologist with EMBL Hamburg’s Schneider Group and EMBL-EBI’s Bateman Group, focuses on a type of brightly colored protein called rhodopsin, which aquatic microorganisms use to harness sunlight as a source of energy.
Now, a newly classified variety dubbed cryorhodopsins, which are unique to cold weather environments, appears to possess particular abilities that allow them to communicate light signals to cells, potentially making them useful in the development of artificial devices that can communicate with the brain.
Rhodopsins
Kovalev’s recent work isn’t the first time rhodopsins have been of interest to researchers studying cell manipulation. Neuroscientists have already employed modified rhodopsins as light-operated switches to control the electrical activity of cells using a technique called optogenetics. They’ve also been used to trigger chemical reactions through light-induced enzymatic activity.
“In my work, I search for unusual rhodopsins and try to understand what they do,” Kovalev recently said. “Such molecules could have undiscovered functions that we could benefit from.”
Color plays a critical role in how rhodopsins behave. Neuroscientists seek a broad palette of rhodopsins to precisely control brain activity, as each variety reflects or absorbs different wavelengths of light due to its unique molecular structure. A pink-orange hue is most common, created by absorbing green and blue light and reflecting pink and orange. However, blue rhodopsins are especially valuable because they can be activated by red light, which penetrates tissues more deeply and non-invasively.
Discovering Cryorhodopsins
After years of research, Kovalev assumed rhodopsins had no more secrets to reveal—until he noticed a peculiar pattern among microbial rhodopsins found in extreme cold, such as mountaintops and glaciers. Unlike the majority of rhodopsins, which are more common in warmer lakes and streams, these cold-environment proteins were nearly identical despite being found in vastly separated locations. That evolutionary consistency suggested an adaptation specifically suited to cold conditions. Kovalev designated this group cryorhodopsins.
Although cryorhodopsins appear in a variety of colors, many are found in desirable blue forms. Kovalev identified a shared structural feature responsible for the blue hue.
“I can actually tell what’s going on with cryorhodopsin simply by looking at its colour,” said Kovalev. “Now that we understand what makes them blue, we can design synthetic blue rhodopsins tailored to different applications.”
Testing Cryorhodopsins
Cryorhodopsins share remarkably similar structures, so much so that even a single atom’s movement can alter their properties. To study them, Kovalev relied on 4D structural biology, X-ray crystallography at EMBL Hamburg’s beamline P14, and cryo-electron microscopy (cryo-EM). Due to their photosensitivity, all research had to be conducted in near-total darkness.
Collaborators tested the proteins within cultured brain cells. When exposed to UV light, the cryorhodopsins generated electrical currents, with varying colors triggering different levels of cellular activity. Further analysis at Goethe University Frankfurt used advanced spectroscopy to understand how cryorhodopsins detect UV light. Surprisingly, cryorhodopsins responded to light more slowly than any previously studied rhodopsins.
“Can they really do that?” Kovalev wondered as the team observed the usual activation of cells in response to UV light by cryorhodopsins.
To further investigate, Kovalev collaborated with researchers in Alicante, Spain, and with his EIPOD co-supervisor Alex Bateman at EMBL-EBI. Their analysis revealed that a gene for an unknown small protein consistently appears alongside the cryorhodopsin gene. The team believes this partner gene may encode a messenger protein that relays UV detections to the cell.
Using the AlphaFold AI tool, the researchers showed that five copies of this protein likely surround the cryorhodopsin in a ring formation. They hypothesize that individual proteins in the ring detach to transmit the signal throughout the cell.
“It was fascinating to uncover a new mechanism via which the light-sensitive signal from cryorhodopsins could be passed on to other parts of the cell,” Kovalev said. “It is always a thrill to learn what the functions are for uncharacterised proteins. In fact, we find these proteins also in organisms that do not contain cryorhodopsin, perhaps hinting at a much wider range of jobs for these proteins.”
Making Use of the New Rhodopsin
The origins of this tandem protein functionality remain unclear, but the team has a hypothesis.
“We suspect that cryorhodopsins evolved their unique features not because of the cold, but rather to let microbes sense UV light, which can be harmful to them,” said Kovalev. “In cold environments, such as the top of a mountain, bacteria face intense UV radiation. Cryorhodopsins might help them sense it, so they could protect themselves. This hypothesis aligns well with our findings.”
Turning this unique new discovery over to improving human conditions is the primary driver for the team’s work.
“New optogenetic tools to efficiently switch the cell’s electric activity both ‘on’ and ‘off’ would be incredibly useful in research, biotechnology, and medicine,” said co-author Tobias Moser, Group Leader at the University Medical Center Göttingen.
“For example, in my group, we develop new optical cochlear implants for patients that can optogenetically restore hearing in patients,” Moser said. “Developing the utility of such a multi-purpose rhodopsin for future applications is an important task for the next studies.”
“Our cryorhodopsins aren’t ready to be used as tools yet, but they’re an excellent prototype,” Kovalev added. “They have all the key features that, based on our findings, could be engineered to become more effective for optogenetics.”
The paper “CryoRhodopsins: A Comprehensive Characterization of a Group of Microbial Rhodopsins from Cold Environments” appeared on July 4, 2025, in Science Advances.
Ryan Whalen covers science and technology for The Debrief. He holds an MA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org, and follow him on Twitter @mdntwvlf.