Tina Boville Directs Evolution to Engineer Nature

BY Lily Helfrich
March 27, 2019

Early Aspirations: Bioengineering Dragons

Location
Pasadena, California
Current Position
Resnick Prize Postdoctoral Scholar, Arnold Lab, Caltech
Educational and Career History
B.A. in Molecular, Cellular, and Developmental Biology & Minor in Chemistry, University of Colorado Boulder; Ph.D. in Biochemistry, Yin Lab, University of Colorado Boulder.
Primary area of research
I evolve enzymes to perform useful chemistry that you don’t find in nature.

Christina Boville, known as Tina to her friends and colleagues, can answer the question, “Did you always know you wanted to be a scientist?” with more certainty than most. “Yeah, I wanted to be a scientist since elementary school,” she says matter-of-factly. Tina can even pinpoint an early interest in bioengineering. “It sounds corny, but I read these books called Dragonriders of Pern with genetically engineered dragons. I got excited by the idea of engineering biology to create something new.”
A fascination with biology and an excitement about its applications stuck with Tina throughout her childhood. These interests pushed her toward a career in science—specifically towards a career in protein engineering and biochemistry. Now, she’s working at the cutting edge of science and, like the Dragonriders of Pern, creating things you wouldn’t otherwise find in nature.

Weaving Industry and Academia

Tina pursued a Ph.D. and is now an academic postdoc, but she took a somewhat non-traditional path to get there: her laboratory experiences before graduate school were all in industry. Working on a process development team at Amgen, Tina learned a rigorous approach to solving scientific problems and to carrying out scientific techniques. Though she wasn’t doing discovery work, her experience at Amgen taught her foundational, valuable skills. “The work I did was very meticulous, and it was a lot like a puzzle. In industry, you really have to find the smartest and most efficient way to tackle problems. It was a good place to learn.”

Where did you grow up?
Parker, Colorado
How do you enjoy spending your time outside of the lab?
I like to do art; mostly painting with acrylics, and some colored pencils. I’ve also done some 3D printing, and I like to play video games.
Can you share a personal fun fact?
I’m an amateur fighter! I practice Muay Thai. People don’t expect it—I’m small and adorable!

Tina worked at Amgen as an undergraduate intern and as a full-time employee, and she later joined a smaller biotech company that was developing a bioreactor for stem cell culture. After a couple of years in industry, Tina decided to pursue a graduate degree. She wanted to be more independent, “to ask bigger questions.” But she was also determined to continue focusing on research with practical applications.

Tina entered the Biochemistry program at University of Colorado Boulder, and she joined Dr. Hubert Yin’s lab. The Yin Lab was a place where she could combine her interests in translational research and basic research. Her goal was to develop drugs to treat autoimmune diseases and related conditions, such as septic shock. She also studied how existing drugs interact with the immune system. One project, of which is she is most proud, led her to the discovery of novel molecular targets for non-steroidal anti-inflammatory drugs (NSAIDs). She found that NSAIDs inhibit caspases, proteins known to mediate programmed cell death—a finding that “could explain some of the negative side effects of these drugs in the human gut.”

As she was approaching the end of graduate school, Tina wanted to pursue an academic postdoc in which she could explore new and different biochemistry. “I have always been really interested in modulating biology to create novel effects. In grad school, I did that with drugs and the immune system. As a postdoc, I wanted to do that with genetic tools; I wanted to engineer nature.”

From Drug Research to Directed Evolution

With her sights set on developing genetic tools to engineer nature, Tina was drawn to the work of Dr. Frances Arnold. Dr. Arnold and her lab had pioneered work on directed evolution, a protein engineering method that mimics natural evolutionary processes, for which Dr. Arnold was later awarded the 2018 Nobel Prize in Chemistry. Using this method, the Arnold Lab was developing novel enzymes for targeted biocatalysis of commercially useful chemical reactions.

“Noncanonical AAs are found in 12% of the highest-grossing drugs; they’re found in agrochemicals or used as probes for protein studies. With more tools, we’ll be able to explore biology in new ways and to develop new chemistry.”

Since joining the Arnold Lab, Tina has worked on developing noncanonical amino acids (ncAAs). “Noncanonical AAs are found in 12% of the highest-grossing drugs; they’re found in agrochemicals or used as probes for protein studies. With more tools, we’ll be able to explore biology in new ways and to develop new chemistry.” The current methods for ncAA development are limited, often resulting in prohibitively expensive products. However, using directed evolution as a tool, Tina and the Arnold Lab hope to create cheaper, easier ways to produce useful ncAAs.

Tina’s research, which takes advantage of directed evolution, focuses on tryptophan synthase, an enzyme that catalyzes the final step of tryptophan biosynthesis. The Arnold Lab had engineered the beta subunit of tryptophan synthase to work without its allosteric partner. This provided a simpler but more versatile tool for the synthesis of noncanonical tryptophans. After Tina joined the lab, she evolved tryptophan synthase further and unlocked its potential to produce new and exciting products. Using the evolved enzyme, she has synthesized β-branched amino acids and fluorescent ncAAs, including 4-cyanotryptophan.

WHY AND HOW DOES THE ARNOLD LAB USE BENCHLING?

I encouraged the Arnold Lab to use Benchling because I think that electronic notebooks are a better alternative to normal paper notebooks. It’s important to have your information stored in a way that is easily accessible from anywhere. In the Arnold Lab, we constantly use Benchling to share data with other project members and collaborators. It’s also an easier way to search lab notebooks and share sequencing data, plasmids, or protocols. Plus, I’m a sustainability person; it doesn’t make sense to use all that paper.

For Tina, the Arnold Lab has been a perfect fit. “I enjoy the challenge of evolving enzymes to do jobs that don’t exist in nature. I also like the mindset that we’ve adopted by mixing biology, engineering, and chemistry. It’s not just that we can make nature do something new, but also that we focus on what is useful.” The applications of directed evolution are nearly endless, but the Arnold Lab has focused much recent work on pharmaceuticals and environmentally friendly applications.

Working Towards Green Bioengineering

Tina has maintained a keen interest in sustainability throughout her career—another interest that drew her to the Arnold Lab. At CU Boulder, she was a “Green Labs Team Lead,” a representative for an environmental advocacy program. Tina helped labs make small behavioral changes that have a big environmental impact. For example, she encouraged labs to turn off and unplug instruments rather than keep them plugged in, to recycle uncontaminated plastic rather than toss it into the autoclave and the trash with contaminated plastic, and to set the freezer to -70°C rather than -80°C. For her efforts, Tina was awarded the 2016 Campus Green Labs Award. Tina believes, “to the extent that they do not compromise the integrity of their science, scientists have a real responsibility to keep track of their consumption and to find ways to be more sustainable.”

At Caltech, Tina was awarded a Resnick Sustainability Institute Postdoctoral Fellowship. Since then, she has been thinking about making her interest in the environment more central to her research and to her career. “I’d like to see biocatalysts broadly used to have an impact on how we approach sustainable chemistry. There’s a better path forward for manufacturing, pharmaceutical development, and other R&D.”

What’s your dream research project?

I’ve been interested in bioleeching because mining is one of the least efficient and most environmentally harmful industries. It would be cool if we could use enzymes to extract metals instead, but we’re a long way from that at the moment.

Who has been an influential mentor for you?

Frances! She encourages us to be fearless. Just because someone thinks your idea is impossible doesn’t mean you shouldn’t do it. You should laugh at them and do it anyway.

Tina ultimately hopes to better both the environment and the biotech industry through her work. To make this happen, she is planning to go back into industry, where she first came to appreciate smart and efficient science.

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Published by Lily Helfrich
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