Old mouse, new tech
New Group Leader brings an exploratory spirit to the Biohub
Many kids enjoy the store-bought science kits that show them how to grow crystals, build a birdhouse, or make giant bubbles. But as a child, Keir Balla was not a fan.
“There was a certain answer you were supposed to get to ahead of time, and once I got to that answer, I felt sort of cheated,” he recalls. Science seemed boring, he thought, because there was no mystery to solve. “I was just confirming what somebody else already knows.”
But an insatiable curiosity about the natural world eventually led Balla back to the world of research, where he now uses innovative techniques to visualize how the immune system adapts and responds to various pathogens. In June, Balla joined the Chan Zuckerberg Biohub as a Group Leader, launching a zebrafish lab devoted to better understanding antiviral immunity in vertebrates.
In this video of a zebrafish taken through the microscope by Keir Balla, circulating blood cells are seen in red, while stationary immune cells appear in light blue.
“I think Keir’s style of doing science and his passion for discovery is going to synergize extremely well with our programs here at the Biohub,” said CZ Biohub President Joe DeRisi. “He’s going to be the perfect addition to an already stellar team.”
Into the unknown
Growing up on the shores of Puget Sound, Balla spent a lot of time outdoors. “I was very much into exploring with friends, whether it was just cruising around on a bicycle through the neighborhoods or scrambling up the waterways,” he says. “I would spend any free moment on a bicycle or climbing upriver and exploring.”
But school was a realm that Balla wasn’t motivated to explore. “School never came easily,” he says. “I was the kid in the back that was always thinking about something else and trying to figure out how I could get out of there and go have some fun.”
Although both of his parents are educators who impressed upon him the importance of education, Balla had no interest in following in their footsteps after graduating from high school.
Instead, a friend helped him get a job at a factory cutting cement boards. There he could make some good money, which “sounded like a much better idea at the time than going to get an education.”
So for several months after high school, Balla would wake up hours before sunrise to catch a ferry to the island where the factory was, for his 6:30 a.m. shift. That cold twilight ferry ride was the best part of the job, he says. “There was often this magical moment where you’d be looking at the water, and then you’d see whales popping up next to you.”
But the novelty of the job—if not that “magical” commute—soon began to fade, and Balla’s urge to explore resurfaced. He thought if he stayed on his current path, he was likely to “slip into a routine where I would stop questioning anything,” he says, “and that just didn’t seem like a long-term plan.”
Becoming a scientist
With the support of his family, Balla was able to attend San Diego State University. But although he knew getting an education was somehow valuable, Balla couldn’t help feeling uninspired and detached as he plodded through his courses. As with the science kits he discarded as a child, “I was dismayed by this feeling that we already know everything out there,” he says. “I felt like it was just my job to just memorize and learn all this stuff.”
Then, Balla fortuitously attended an afternoon seminar in which a scientist described his research on the immune system. That talk completely upended Balla’s outlook on science, giving him “the sense that there’s still more out there to learn,” he says. “That might be obvious to many people, but it wasn’t obvious to me at the time.”
Now infected by the research bug, after graduating from SDSU Balla accepted a lab position at the University of California, San Diego, eventually pursuing a Ph.D. in Emily Troemel’s group at UCSD. As a doctoral student, Balla studied microbes that infect C. elegans, a microscopic roundworm and versatile model organism that’s widely used in biology.
This work fostered an interest in evolutionary aspects of infection, which Balla expanded upon as a postdoc at the University of Utah under the mentorship of evolutionary geneticist Nels Elde. In the Elde lab, Balla began working with zebrafish, which are a popular vertebrate species among researchers because their transparent bodies allow the fluorescent tags used in molecular biology to be easily seen under the microscope.
Balla engineered fish in which the antiviral immune system fluoresces when activated, providing a clear visual signal at the onset of a viral infection. Using this tool he has discovered several naturally occurring viruses affecting zebrafish that had previously escaped the notice of scientists.
Now, with a diverse set of experimental tools in hand, Balla is broadening the view to visualize the progression of infection and immunity in zebrafish at multiple scales—from the subcellular to the epidemiological.
The Biohub’s ‘scrappy’ science
Balla says his research goal is “to provide a visual account of what infection is, in all of its senses, from the very beginning through all different courses of how an infection can turn out: whether an organism gets sick or doesn’t, and then what happens after the infection has been taken care of.”
For DeRisi, this means that “when combined with the Biohub’s proteomics, genomics, and computational microscopy research, Keir’s work will produce a picture of what infection looks like at the whole-organism level, at a resolution and level of detail that’s really never been seen before.”
Because Balla’s methods draw from cell biology, microscopy, and basic infectious disease research, his new lab is a silo-buster, straddling both the Infectious Disease and Quantitative Cell Science initiatives at CZ Biohub.
“I want to go after the biggest, most profound questions that I can, given the unique advantages of the Biohub, and with a team that has been described to me as a ‘scrappy band of geniuses,’” Balla says. “It’s a scientific dream, and I can’t imagine a better place to be.”