Arctic Microbes Unveil New Blue Rhodopsins: Potential Game-Changers in Optogenetics and Neurology

Kirill Kovalev, an EIPOD Postdoctoral Fellow at EMBL Hamburg's Schneider Group and EMBL-EBI's Bateman Group, has discovered a unique group of rhodopsins in cold environments such as Greenland's glaciers, the Tibetan high mountains, and Finland's ice-cold groundwater. These molecules, which he named 'cryorhodopsins,' could revolutionize neuroscience through their potential applications in optogenetics—the technique that uses light to control and study neurons. Rhodopsins are proteins commonly found in aquatic microorganisms, enabling them to convert light into energy. Kovalev's interest was piqued when he identified a distinct feature shared by rhodopsins in extremely cold climates, despite their geographical separation. This discovery suggested that these proteins play a crucial role in survival in such environments. Kovalev and his team conducted extensive structural biology research to understand the molecular characteristics of cryorhodopsins. Unlike typical rhodopsins, which are mostly pink-orange and absorb green and blue light, some cryorhodopsins display a blue color, making them highly valuable for optogenetics. Blue rhodopsins are sought after because they can be activated by red light, which penetrates tissues more deeply and less invasively than other wavelengths. Using advanced spectroscopy, the team found that cryorhodopsins respond to UV light, a trait that sets them apart from other rhodopsins. When brain cells expressing cryorhodopsins were exposed to UV light, they generated electric currents. Subsequent green or UV/red light exposure altered the cells' excitability, demonstrating the potential of cryorhodopsins to serve as both 'on' and 'off' switches for neuron activity. This versatility could make cryorhodopsins invaluable tools in medical research and biotechnology. For instance, Tobias Moser, a Group Leader at the University Medical Center Göttingen, is developing optical cochlear implants to restore hearing through optogenetics. He highlighted the importance of designing more effective optogenetic tools, which cryorhodopsins could contribute to significantly. Further investigation revealed that the cryorhodopsin gene is accompanied by a gene encoding a small protein, which may act as a messenger. The team used AI tools like AlphaFold to predict that five copies of this small protein form a ring and interact with the cryorhodopsin, potentially relaying the UV light signal to the cell interior. This finding suggests that cryorhodopsins might help microbes detect and protect themselves from harmful UV radiation, a critical need in cold environments where UV exposure is intense. Kovalev's breakthrough required overcoming significant technical hurdles. He employed a 4D structural biology approach, integrating X-ray crystallography and cryo-electron microscopy (cryo-EM) with protein activation by light. The unique setup at EMBL Hamburg's P14 beamline was instrumental in his research, allowing precise manipulation of light conditions. Due to the extreme light sensitivity of cryorhodopsins, the team had to work in near-total darkness, adding another layer of complexity to their experiments. The discovery of cryorhodopsins underscores the importance of exploring remote and challenging environments for unique biological solutions. These proteins could provide new insights into microbial adaptations and offer innovative tools for controlling and studying neuronal activity, advancing fields like optogenetics and potential medical applications. Industry insiders laud Kovalev's work, emphasizing the potential impact on both basic research and clinical applications. The ability to control cellular activity with higher precision and less invasiveness could lead to breakthroughs in understanding and treating neurological disorders. Kovalev's interdisciplinary approach, combining physics, structural biology, and advanced AI techniques, sets a new standard for scientific exploration in the realm of biotechnology. Scale AI, with its expertise in data labeling and advanced computational methods, could play a pivotal role in further analyzing and optimizing these newly discovered proteins for practical applications. Kovalev's collaboration with his multidisciplinary team highlights the growing importance of cross-sector innovation in addressing complex scientific and medical challenges.