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June 13, 2024
Above: Mary Fairbanks BS’23, biology

A DNA repair system known as the GO DNA repair system removes oxidized guanine. This helps protect the system from mutating, and while scientists understand how it works, the origin of this mechanism isn’t well understood.

That’s where the Horvath Lab comes in and, in particular, Mary Fairbanks BS’23. She and her team in the School of Biological Sciences at the University of Utah explores structural biology and biochemistry by researching microbes from the Lost City Hydrothermal Field, an area of marine alkaline hydrothermal vents located in the Atlantic Ocean.

Like Fairbanks, who gained hands-on experience creating experiments and directly participating in research, other lab members worked on the project as undergraduates before graduating. They include Payton Utzman BS’22 and Briggs Miller BS’22 who along with Fairbanks and graduate student Vincent Mays researched microbes that live at the bottom of the ocean where there is little oxygen and even less sunlight. Because of the lack of oxygen in the environment where these microbes thrive, the fact that researchers found GO DNA repair genes is important: it shows a need for genes that repair DNA that has been put under stress from oxygen. Their research was recently published in PLOS.

Acting like a scientist

“Working in Dr. Horvath’s lab has taught me how to be curious and be dedicated to a project,” Fairbanks says. “Being able to design my own experiments has given me the opportunity to act as a scientist. I have grown through research and it continues to expand my view of the possibilities of innovation.”

Horvath first learned that one of the GO repair genes called MutY might be present at the Lost City Hydrothermal Field from a student in his Molecular Biology of DNA Lab course, Emily Dart HBS’16. Horvath knew that Dart was working with William Brazelton, a fellow biologist who had recently collected DNA from Lost City. Searching that Lost City DNA, Dart and her teammates found genes encoding at least portions of MutY.

“Since that first analysis,” says Horvath, “the sequence technology improved, more samples from another expedition generated metagenomes with better coverage, and we now have functional tests that show these MutYs from the bottom of the ocean actually work to prevent mutations in lab strains of bacteria.” That these discoveries stemmed from basic science research by undergraduates, he says, is “something that I am very proud to celebrate!”

How life might evolve on other planets

GO DNA repair genes are advantageous even in environments without much oxygen. Since hydrothermal fields like the Lost City Hydrothermal Field are similar to the environment of early Earth, this indicates that these repair systems evolved before the Great Oxidation Event.

Fig 5. LCHF MutY chemical motifs. (A) Conservation and diversity of MutY-defining chemical motifs are depicted with a sequence logo for the 160 LCHF MutYs. These motifs are associated with biochemical functions including DNA binding, enzyme catalysis, attachment of the iron-sulfur cofactor, and recognition of the damaged OG base.

Insights like this can help develop models of how life might evolve on other planets. Planets that lack the abundance of oxygen that modern Earth has may have life evolving in a similar way to microbes that live near hydrothermal vents. Since these microbes have repair systems that deal with oxidative stress, it’s reasonable to consider that life on other planets may as well.

The group also discovered the role that these repair genes, including MutY, play in hydrothermal microbes, by associating GO DNA repair with metabolic pathways. These pathways produce oxygen as a byproduct, so MutY may play a part in fixing DNA damage caused by metabolic processes.

Life on other planets may take many different forms, and similarly, learning science also takes many forms beyond the classroom. “I’ve been encouraged to ask questions and explain findings to form a cohesive pattern that tells a story,” says Fairbanks. She credits the lab experience as helping her “see a project from start to finish. I have been able to improve my critical thinking skills and laboratory technique, as well as adapt to change.”

That adaptation to change is a good lesson to learn as empirically observed far below the surface of the ocean both also on a personal level for Fairbanks and her young researcher cohorts. Findings such as these may show how DNA-based life forms rely on fixing damage caused by oxidation, even in environments without oxygen. And they give scientists a clue as to how life may look on other planets by forming models of life in environments unlike Earth’s. But the “findings” are clearly internal as well for young, developing scientists who will never forget their time examining and interpreting data in the Horvath Lab.

As Martin Horvath intones of this research, “Life finds a way.”

As do young minds like those found embodied in Mary Fairbanks who, now headed for a career in the medical field, concludes, “I believe my experience in research will make me a more open-minded thinker.”

by CJ Siebeneck