Jenna Guthmiller was exposed to the ideas of immunology early. Growing up, her parents taught her how vaccines work and are administered, and, by studying animals, she learned about disease and the ways immunity is passed from parent to child. Guthmiller’s parents were experts in the science of these ideas, but they weren’t professors or doctors. Instead, Guthmiller’s parents ran a dairy farm.

“One of my favorite things was when we would vaccinate our animals,” said Guthmiller. “We’d talk about what it was doing to promote their health and how immunity is transferred from mother to infant.”

Even before Guthmiller, currently a postdoctoral researcher in the Biological Sciences Division at the University of Chicago, had a clear picture of what it meant to be a scientist, she knew she wanted to learn more about the ideas she had been exposed to on her South Dakota farm. Guthmiller entered college at South Dakota State University without much of a plan beyond knowing that she liked and had an aptitude for science. But once she had her first taste of laboratory work, she was hooked.

“I changed my major probably three times my first year of college,” recalled Guthmiller. “But when I took a microbiology course, I said, ‘Oh yeah, this is it. This is what I’m going to major in.’”

In that course, Guthmiller remembers being randomly assigned an unknown bacteria sample and being asked to figure out what it was, using a toolkit of tests. Instead of intimidating her, this broad question thrilled her.

“It was the most fun thing I ever did in a lab course. It was solving a puzzle with something biological,” she said. “I changed my major soon after.”

Becoming a researcher

From then on, Guthmiller found as many opportunities as she could to work in labs, both inside and outside her university. Guthmiller even worked at a biotech company that commercialized colostrum.

“The first couple of milks after a mammal, like a human or a cow, gives birth is colostrum,” explained Guthmiller. “It’s this thicker, fattier milk that is really important for both passive immunity and providing the first nutrients for the baby.

In that lab, Guthmiller analyzed the colostrum, studying its quality and immune system benefits, for development as a supplement for human babies. She also worked for a summer at the USDA Meat and Animal Research Center in Nebraska. There she was exposed to laboratory techniques such as polymerase chain reaction (PCR)— a method of amplifying the information in a small sample of DNA— and cloning, which is used to make copies of genes. That position also gave her the opportunity to leave South Dakota for the first time and devote herself completely to research.

In her junior year of college, Guthmiller began work in the research lab of Professor Feng Li. Despite the defining experiences she had had before, she considers this the role that cemented her commitment to research.

“He was so excited about science and a really great mentor,” Guthmiller said. “Working in Dr. Li’s lab really pushed me towards staying in microbiology, and specifically virology.”

In addition to the experience Li offered Guthmiller in the lab, Li supported her in applying to graduate school, helping her navigate the process.

After graduating from college, Guthmiller started graduate school at the University of Oklahoma Health Sciences Center. She then finished her PhD in four years— a short timeline, particularly for someone doing experimental work. She partly chalks her pace up to how she was used to working as a kid.

“It was the dairy farm ethics of working 7:00 AM to 7:00 PM,” she joked.

More seriously, Guthmiller credits much of her success in graduate school to joining Dr. Noah Butler’s lab, a young assistant professor now at the University of Iowa.

“He was able to be very hands on with me, helping me craft ideas and find answers to experimental questions,” Guthmiller explained.

Guthmiller’s graduate work was on immune responses to a type of parasite, called Plasmodium, that causes malaria. Guthmiller studied humoral immunity—the type of immunity that is facilitated by molecules, such as antibodies, outside of cells. In the case of Plasmodium infection, the antibody response is short-lived. Guthmiller identified mechanisms that would promote long-lived responses instead.

Now, Guthmiller works as a post-doctoral researcher at UChicago, in the lab of Patrick Wilson, Professor of Medicine. She still studies antibody responses, but in a different model system.

“I changed fields to a fair degree and now study humoral immunity against influenza viruses,” explained Guthmiller. “It sounds similar, but it is a completely different class of pathogens.”

In her current work, Guthmiller characterizes flu antibodies, to better understand where they target and how they function. This work is based on a discovery that Wilson’s team made that the 2009 pandemic H1N1 virus induced antibodies against parts of the virus that rarely change. Her research revealed antibodies targeting four distinct parts of the influenza viruses that are conserved across H1N1 viruses, and are therefore excellent vaccine targets. However, her research also showed these antibodies tend to be polyreactive, meaning that they can bind to unrelated molecules, including self-antigens—molecules that originate in the body and should not be attacked by the body’s immune system. Because of this, these broadly reactive flu antibodies may be difficult to induce, as humans have immune barrier to prevent attacking their own self-antigens.

Guthmiller’s work has also focused on understanding antibody responses against the FDA-approved flu vaccines. For example, she co-led a study that identified differences in protection between seasonal vaccination and natural infection. She also discovered that flu virus vaccines grown in eggs can, in humans, induce antibodies against an egg-associated sugar, as opposed to the flu virus itself.

An unexpected interruption brings new opportunities

Last year, as SARS-CoV-2 brought the world to a halt, Guthmiller’s research was no exception. At first, she was frustrated, as her own projects and plans had to be put on hold. But with her skills and knowledge, Guthmiller was in a unique position to contribute to our understanding of the virus and how our immune systems respond to it and can be harnessed to fight it.

“I jumped on some COVID projects,” she said, “which became instrumental in some of the serology work that came out of UChicago.”

Serology is the study of the proteins within blood plasma and is important for understanding immunity. With their ability to study antibodies, the Wilson lab and Guthmiller investigated the magnitude and specificity of antibodies induced by SARS-CoV-2 infection and were instrumental in UChicago’s convalescent plasma effort.

Even with these new projects, though, Guthmiller was still faced with more free time than she was used to. She didn’t put it to waste.

“One thing I did was sit down and organize my data,” she said. “In doing that, I realized I had a couple of papers I could write with what I already had.”

During the past year, she published five first-author research manuscripts and two literature reviews. She also took time to look ahead and plan for future projects and her own independent research career.

“I wrote a career transition NIH grant—a K99, and I applied for faculty positions,” she said, “to continue my work on studying antibodies against the flu.”

The grant got a perfect score and was recently funded. Guthmiller was also recruited to the University of Colorado Anschutz Medical Campus. She is starting her laboratory there in 2022, where her research program will focus on understand the host-virus interactions that mediate protective antibody responses.

By Amanda Parker, PhD

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