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Summer 2022

Cover Story

 

Betül Kaçar is a self-described gözü kara. The Turkish term refers to people from the Black Sea region of the country, but it has another translation as well.

“It means bold-eyed or fearless,” says Kaçar, an assistant professor in the Department of Bacteriology. “It means that I don’t know my place. I never did, and I think that served me well. It put me in a mindset that I could do anything.”

That dauntless disposition propelled Kaçar from her humble roots in Turkey to the forefront of astrobiology. A highly interdisciplinary field, astrobiology examines the origin, evolution, and distribution of life in the universe. Through groundbreaking approaches in her research group and leadership roles in prominent NASA initiatives, Kaçar is rewinding Earth’s clock billions of years to try to understand how life’s emergence and its early biological innovations may assist in finding life beyond our planet.

‘Set Yourself Free’

Kaçar’s career in astrobiology would seem as remote to her childhood self as the celestial bodies that NASA is probing for signs of life in our solar system and beyond. She grew up in Istanbul, the child of parents from the Black Sea region who didn’t complete elementary school. “There was a very clear message in my family,” she says. “If you want your story to be different, you need an education. It’s the only way to set yourself free.”

Headshot of Betül Kaçar.
Betül Kaçar, assistant professor of bacteriology, is pictured in her research lab.

Her world started expanding in high school, where she was exposed to poetry, arts, science, and literature, which gave her a sense she was part of a larger picture. While studying for her bachelor’s degree in chemistry at Marmara University in Istanbul, Kaçar seized every opportunity to learn and do more. “I would camp out in tourist areas to offer to show tourists the museums and other sites, so I could ask about and learn about their cultures,” she says.

In the summer of 2002, she volunteered at an international meeting on Parkinson’s and Alzheimer’s diseases. The experience introduced her to the field of biomolecular chemistry — and changed her life. “I was amazed that scientists would come from all over the world to lock themselves in these seminar rooms for days to talk about a single molecule and what it did,” Kaçar says. “I found that interaction, personal level of engagement, and devotion extremely inspirational. I wanted to be on that stage and contribute to that knowledge.”

She next applied for a Howard Hughes Medical Institute summer undergraduate research scholarship, which led to her first trip out of Turkey to study proteins at Emory University under the guidance of Pat Marsteller, now a professor emerita of biology. The summer internship and Marsteller’s influence changed her life, Kaçar says. The experience gave her the tools she would need to deal with the challenges later in her career. And it exposed her to protein engineering, the idea of playing with proteins simply for the sake of seeing and understanding what happens to them. “It blew my mind,” she says. “It was amazing. There was no going back after that for me.”

Kaçar returned to Emory the following year to pursue her Ph.D. in biomolecular chemistry. She has lived and worked in the United States ever since. “I was only 20,” she says. “I didn’t know anyone. But sometimes you must create your own roots and make a life for yourself.”

‘You Have to Look at Its Past’

Kaçar’s research compared the expression of an enzyme called monoamine oxidase in zebra fish with its expression in humans. As she moved through her Ph.D. program, her questions grew bigger and bigger. “I wondered, ‘Zebra fish have this enzyme; humans have this enzyme. Where is this enzyme coming from? What is the common origin?'” she says. “I started studying its phylogeny [evolutionary development and diversification] to understand its evolutionary route. It was evident to me that if you want to understand an enzyme’s function today, you have to look at its past.”

Ever eager to learn more, she started attending meetings in the evolutionary biology department, one floor below the lab where she worked. She quickly realized a fundamental challenge: “The majority of life’s history and innovations are lost,” she says. “We are dealing with whatever is left to us today. We are not capturing the full diversity of proteins when we ignore their past. We tend to think of the past as a failed state and that things get more optimal as they evolve, but that is not necessarily true. There is a past that we don’t yet understand, but we should.”

The readings Kaçar first encountered at the time introduced her to the origins of life and evolution, and she was hooked. “I thought, this is what I want to do,” she says, “It was my eureka moment, my calling.”

Kaçar applied for a two-year postdoctoral fellowship with NASA’s astrobiology program with a radical research proposal: She would create a “molecular time machine.” Using a process called phylogenic inference, she would develop synthetic ancient proteins, insert these resurrected sequences into a modern bacterial genome, and then evolve them experimentally in the lab. The goal would be to see if she could repeat an ancient protein’s evolution in a way that matched its own natural history.

Colleagues warned her that her unorthodox proposal was a career killer. But Kaçar, ever a gözü kara, didn’t listen. “I was in it to do the science that interests me,” she says. “I knew that, after my high school and college degrees, I had already made it further than anyone in my family had done. So, the worst thing, I thought, would be that I would try, and fail, to figure out life’s origins. That, to me, is a success.”

And succeed she did: Her proposal was accepted. She started her fellowship in 2012, which launched a rewarding and ongoing affiliation with NASA, a decade of innovative research, and a dedicated outreach effort to encourage young women around the globe to pursue STEM fields.

‘We Are Life and Its Origin in the universe’

Kaçar herself was surprised that NASA was interested in biology. “In my mind, it was a space-related group that would be interested in only astronomical questions,” she says. But NASA funded its first astrobiology project just one year after its founding in 1958. (Back then it was called exobiology.) Forty years later, the NASA Astrobiology Institute was established to provide a scientific framework for all flight missions and to advance astrobiology research and training programs in concert with national and international science communities.

NASA’s astrobiology research focuses on three key questions: How does life begin and evolve? Does life exist elsewhere in the universe? What is the future of life on Earth and beyond?

Kaçar, naturally, focuses on that first question. “Astrobiology aims to understand the origin of life in the universe,” she explains. “We forget that’s us, right? We are life and its origin in the universe, the only one we know of so far. So, we invest a lot in understanding our own origins and our own planet. We have to understand what we have here if we want to then go and find something else out there.”

At NASA, Kaçar found an environment that was more inclusive, diverse, and interdisciplinary than anything she’d seen. “Through NASA, I met physicists, geologists, chemists who knew RNA inside out, experts who studied Martian surfaces, and we were all a part of the same community,” she says. “I was made to feel welcome. My questions weren’t ridiculed; they were celebrated. I felt at home.”

‘Full of Surprises’

Throughout Kaçar’s decade of research — at the NASA Astrobiology Institute, Harvard University, University of Arizona, and now the University of Wisconsin–Madison — her molecular time machines have produced intriguing insights into not just how these ancient proteins may have changed themselves but how, in turn, they could have changed the environment.

For example, RubisCO is a key enzyme in the carbon fixation and photosynthesis process and thought to be one of the most abundant proteins on Earth. Kaçar studied as many types of RubisCO as possible to reverse-engineer the enzyme to its ancestral form. While RubisCO evolved over time, the carbon isotope that RubisCO converts from inorganic to organic carbon stayed uniform, despite billions of years of geological events, ecosystem turnover, and evolutionary innovation. “That’s not what you would expect,” she says. “Natural selection is full of surprises.”

Furthermore, she found potential changes in the RubisCO enzyme that she thinks are implicated with the Great Oxygenation Event. During this turning point in Earth’s history some 2.4 billion years ago, oxygen started building up in the seas and atmosphere of an anaerobic planet. Without that event, our current oxygen-rich environment — and life as we know it — might not exist.

NASA graphic depicting Kaçar riding a T-Rex dinosaur.
Betül Kaçar was featured in this NASA graphic novel series in which her cartoon avatar rides a T-Rex and gathers ancient enzyme samples. Artwork by Aaron L. Gronstal

“Betül has brought an understanding at a molecular level of the evolutionary events of life in Earth’s history,” says Shawn Domagal-Goldman, an astrobiologist who has known Kaçar since she was a postdoc at the NASA Astrobiology Institute and is now the branch head for the Planetary Systems Laboratory at NASA’s Goddard Space Flight Center. “She’s probably the foremost thinker on what that implies for what possibilities are out there for life on other worlds, whether in our solar system or beyond. She is one of the people who helps us understand what is possible in the first place. We incorporate her insights into our expectations for whether certain biological processes might be happening elsewhere and if the byproducts of those processes could be detectable out there.”

The acceleration of space exploration technology increases the significance of Kaçar’s work. “We are able to see further, see clearer, visit planets in our solar system, and bring samples back to our own world,” she says. “We will be facing so much data over these next two decades. We will be tested to interpret what it all means.”

Kaçar’s research methods and results have established her as one of astrobiology’s shining stars. She has received the Stanley Miller Early Career Award from the International Society of the Study of the Origin of Life, the NASA Early Career Faculty Award, and the Scialog Fellowship for Signatures of Life in the Universe. Her work has received funding support from NASA, the National Science Foundation, the Human Frontiers in Science Advancement Program, and the John Templeton Foundation. She’s even featured in an issue of NASA’s graphic novel series Astrobiology: The Story of our Search for Life in the Universe. Her cartoon avatar rides a T. Rex, climbs the phylogenic “Tree of Life” (which graphically illustrates evolutionary relationships among biological entities), and scoops up RubisCO samples from ancient Earth.

“The most successful astrobiologists are collaborative. Betül is phenomenal at that,” says Domagal-Goldman. “She has tremendous expertise in understanding the history of evolutionary events on Earth and does a great job at collaborating with people from other backgrounds to find other applications for the knowledge that she brings to the table.”

‘A Long Tradition and History’

There was tremendous excitement and anticipation about Kaçar when she joined the Department of Bacteriology at CALS in summer 2021. She transitioned from the University of Arizona, where she was an assistant professor in the departments of molecular cell biology and astronomy. At UW, she was the first professor recruited as part of a cluster hire focusing on the origins of life, a new interdisciplinary focus for the university that bridges bacteriology with the astronomy and geoscience departments.

Kaçar had been front and center on the bacteriology department’s radar since January 2021, when she gave a tremendously popular virtual seminar about reconstructing ancient biosystems as a way to explore life’s origins.

Betül Kaçar and Kaitlyn McGrath looking at and discussing Petri dishes.
Betül Kaçar, left, and University of Arizona graduate student Kaitlyn McGrath look at and discuss Petri dishes containing cultures of ancient DNA molecules in Kaçar’s research lab.

“We had around 130 people from departments as disparate as philosophy to bacteriology, chemistry to astronomy,” says Katrina Forest, chair and professor in the Department of Bacteriology. “It was an extremely exciting indication of how popular her work could be on this campus . . . She certainly brings energy, enthusiasm, and creativity, as well as a new research approach and research area.”

For Kaçar, the bacteriology department was a natural fit for her work. In particular, she saw it as a proper home for the NASA Center for Early Life and Evolution, which hosts the MUSE (Metal Utilization and Selection Across Eons) Consortium, as well as one of NASA’s newly created Research Coordination Networks on Early Life. Kaçar serves as the director of these five-year multi-institute endeavors, funded by a highly competitive and prestigious NASA Interdisciplinary Consortia for Astrobiology Research Award and the NASA’s Science Mission Directorate.

MUSE focuses on the evolution of metal use on Earth — specifically the biochemistry of carbon and nitrogen acquisition throughout time. The project looks at why life relies heavily on certain metals, such as iron, but not others, such as zirconium, and retraces the path of element selection during Earth’s evolution to try to better understand Earth’s unique form of life. The Center for Early Life and Evolution is after a big question: After life originated, what happened next? Kaçar’s interdisciplinary team will focus on the first 2 billion years of life’s history on Earth, illuminate early cellular innovations, and bridge molecular and microbial astrobiology with future space missions.

In addition to her research, Kaçar will be leading a new summer field course titled “Alien Planet Analogs on Earth.” It will familiarize students with searching for and interpreting microbial biosignatures through simulated surface lander missions at sites in Utah and Montana.

Petri dishes containing cultures of ancient DNA molecules.
Petri dishes containing cultures of ancient DNA molecules.

“Nothing makes me happier than growing these initiatives here, especially because the bacteriology department has a long tradition and history of exploring nitrogenases,” Kaçar says, citing the enzymes that are integral to all known forms of life.

For more than a century, the bacteriology department has been a world leader in the study of biological nitrogen fixation, the conversion of nitrogen gas into the ammonia that plants use to make their proteins and DNA. Nitrogenase is critical to this process. Luminaries such as E.B. Fred, Ira Baldwin PhD’26, and Elizabeth McCoy published the definitive text on nitrogen fixation in 1932. In the 1970s, Winston Brill, former Vilas Chair Professor of Bacteriology, worked out the basic biochemistry and identified more than 20 genes required for nitrogen fixation. (See “Of Mutant Wranglers and Slime Whisperers” in Grow, Fall 2020.)

“Betül’s work is really an example of thinking outside the box,” Brill says. “She seems to be willing to take big risks in her research, the kind that lead to big breakthroughs.” After attending one of Kaçar’s virtual lab meetings early in 2022, Brill was so impressed by what he’d heard that he admits to gushing to his wife, “I wish I could be a student in that lab!”

‘Your Knowledge Will Be Your Power’

Outreach has always been a top priority for Kaçar. She is eager and always willing to spread the word about the astrobiology field and to encourage young women of all ages around the globe to believe in themselves and pursue STEM fields. “I never thought I would end up on this journey,” she says. “It is my responsibility to give back.”

In 2012, as her astrobiology career was taking off, she cofounded SAGANet, an online education platform that offers curious minds a way to ask fundamental questions about life in our universe. SAGANet connects students worldwide with summer astrobiology programs, online mentors, and the latest research in the field. One of Kaçar’s current undergraduates found her way into the astrobiology field through SAGANet.

Kaçar has delivered talks everywhere from the Boston Science Festival to the main stage of TED2021 to the Library of Congress. She has been profiled for the Smithsonian’s “The Scientist Is In” series and appeared on numerous podcasts and TV programs, including a PBS documentary on the origins of life. She frequently participates in STEM mentoring meetings and, as the parent of a four-year-old, connects with other women and mothers in science.

One of her proudest moments came last year when she made a presentation on the future for women and girls in science to the United Nations Commission on the Status of Women. She pointed out how the COVID-19 pandemic further deprived girls around the world of learning opportunities that could advance their educational path.

“We should not forget that there is a part of the world that will pay the price of the pandemic throughout their lifetime,” she says. “So many girls over the past two years have missed out on perhaps once-in-a-lifetime opportunities. I think about that summer I attended the scientific conference in Istanbul. What if there was a COVID outbreak that year and I couldn’t go? That turning point would have been gone.”

Kaçar encourages leaders to create even more opportunities for that “invisible population” to make up for lost time. And to girls, she speaks as a gözü kara, from experience and from the heart: “Your knowledge will be your power. Fight for your right to receive an education and an equal future for everyone. There will be a lot of roadblocks along the way. Stay true to yourself, surround yourself with people who inspire you and who get you. When in doubt, be your own role model, and make decisions that your childhood self will be proud of.”

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