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Unveiling Life’s Resilience: How AI and Extreme Microbes Illuminate the Secrets of High-Pressure Adaptation

An enhancement from a Google Artificial Intelligence tool has aided researchers in understanding how the proteins of a microorganism that thrives in heat manage to endure the extreme conditions found in the Earth’s deepest ocean trenches. This discovery provides valuable insights into how these essential components of life may have developed in the early Earth environment.
An enhancement from a Google Artificial Intelligence tool has aided researchers in understanding how the proteins of a microorganism that thrives in heat manage to endure the extreme conditions found in the Earth’s deepest ocean trenches. This discovery provides valuable insights into how these essential components of life may have developed in the early Earth environment.

The results, recently published in PRX Life, are expected to stimulate further investigations into the fundamental mechanisms of proteins and the potential for life on other planets. They also serve as a notable example of how artificial intelligence can significantly accelerate research that otherwise might have taken decades.

“This study helps us understand how to engineer new proteins that can handle stress, in addition to offering clues about which types of proteins are likely to survive in high-pressure settings, such as the ocean floor or extraterrestrial environments,” remarked Stephen Fried, a chemist from Johns Hopkins University who co-led the research.

The research team subjected Thermus thermophilus, a microbe commonly utilized in studies due to its heat resistance, to laboratory conditions that mimicked the pressures found in the Mariana Trench. The experiments showed that many of its proteins are resilient to these pressures because they possess built-in flexibility with extra space within their atomic structures, enabling them to compress without breaking down.

The function of a protein is determined by how its building blocks, or amino acid sequences, “fold” into three-dimensional structures. However, these structures are often sensitive to alterations in temperature, pressure, and other environmental factors, as well as biochemical and genetic abnormalities, which can lead to faulty shapes that lose functionality.

Analysis revealed that 60% of the proteins in the bacteria maintained their structure under pressure, while the others succumbed and deformed at locations crucial for biochemical functions. These insights may explain how various organisms manage to survive in conditions that would be lethal to most life forms.

“Life has undeniably evolved to adapt to diverse environments over billions of years, but evolution can often seem almost magical,” Fried stated. “This research delves into the biophysics of how adaptation occurs, revealing that it stems from straightforward geometric solutions in the 3D arrangement of these proteins’ building blocks.”

The research underlines the significant role artificial intelligence can play in scientific advancements, Fried noted. By utilizing Google’s AlphaFold tool, the team was able to map the pressure-sensitive regions of T. thermophilus’ complete protein set. This AI tool predicted the structures of over 2,500 proteins in the organism, facilitating the evaluation of the relationship between their configurations and their resilience to pressure changes, which would have otherwise taken many years of experimental work to achieve, according to Fried.

While the microbe is recognized for its ability to survive in hot springs rather than deep-sea pressures, the findings could provide insights into the poorly understood deep ocean life, as mentioned by author Haley Moran, a chemist from Johns Hopkins who focuses on “extreme” organisms.

“Many experts suggest that if we are to discover extraterrestrial life, it will likely be found in the deep oceans of some celestial body. However, our understanding of life in our own oceans is incomplete, as there are numerous species that not only tolerate but thrive in conditions that would be fatal to us,” Moran explained. “We are examining proteins, which are fundamental components of life, under extreme conditions to understand how they may adapt and expand the possibilities of life.”

The results also underscore how high-pressure experimentation could uncover additional molecular functions that have yet to be identified in other organisms. Previously, it was thought that pressure would need to be significantly higher than those found at the ocean’s floor to affect a protein’s biochemistry, noted author Richard Gillilan, a chemist from Cornell University who contributed to the high-pressure experiments.

“We were genuinely surprised; as we continued to validate our data and examine specific molecular structures, it became evident that we were uncovering a treasure map,” Gillilan said. “This research opens a new avenue for exploring structural and biophysical aspects, potentially leading to drug discovery as well.”

The team plans to conduct further experiments on other organisms that thrive under the high-pressure conditions of the deep ocean.

Additional contributors include Edgar Manriquez-Sandoval and Piyoosh Sharma from Johns Hopkins.

This research received support from the National Science Foundation, NSF Division of Molecular and Cellular Biology, the National Institutes of Health, the National Institute of General Medical Sciences, the Albstein Foundation for Brain Research, and New York State’s Empire State Development Corporation.