CU Boulder PhD student Emily Kibby has won the Harold M. Weintraub Graduate Student Award in recognition of her work researching bacterial immune responses

There are certain advantages to being a one-celled organism with no nucleus. In general, reproduction happens fast, and thus evolution does, too.

Take bacteria, for example: A bacterium can be invaded by a phage, which is a virus that infects and replicates only in bacterial cells, and within several generations—which can emerge in a single day—the bacteria may have evolved immunity to that virus.

“We’re so evolutionarily outclassed by bacteria,” says Emily Kibby, a PhD candidate in the University of Colorado Boulder Department of Biochemistry and member of the Aaron Whiteley Research Group. “They can evolve so much faster, and they’re the real biochemical innovators of life on this planet. I think we have so much to learn from them.”

In fact, since joining Whiteley’s research group in 2020 for her graduate studies, that’s exactly what Kibby has done—work to understand how eukaryotes (organisms whose cells contain a nucleus encased in a membrane), including humans, have acquired and adapted bacterial immune proteins for their own purposes.

Her work recently was recognized with the Harold M. Weintraub Graduate Student Award, given by the Fred Hutch Cancer Center to honor outstanding achievement during graduate studies in the biological sciences. Kibby and her fellow winners were chosen for the quality, originality and scientific significance of their research and will be honored at a symposium May 3 in Seattle.

“Emily is highly deserving of the Weintraub award because she is a dedicated scientist whose fearlessness and innovative thinking have allowed her to open new research areas in my lab,” says Aaron Whiteley, a CU Boulder assistant professor of biochemistry.

“One of the most impressive aspects of her thesis work was a decision in her fourth year to undertake a new project in computational biology. She demonstrated independence and resourcefulness, seeking out necessary expertise from other investigators and in the literature. It can be very hard to break into new disciplines, and I am extremely proud of her accomplishments. I expect nothing short of amazing things to come!”

Bacterial origins

Kibby credits excellent AP biology and AP chemistry teachers at her Wisconsin high school with nurturing her ever-growing interest in science. It also helps that both of her parents are teachers, she says.

So, when she was considering what to study as an undergraduate at Swarthmore College, “I decided to head down the middle between biology and chemistry,” she says. “I’ve just always been fascinated by the molecular mechanisms that make life possible. We have this incredible amount of molecular detail on cellular processes, but there’s still so much more to learn. That’s always what’s been so exciting to me, that we know so much but there’s this vast amount still to learn.”

She fell in love with bacteria during her undergraduate summers working in Helen Blackwell’s lab at the University of Wisconsin-Madison, where an aim is to devise novel chemical tools to decode and interfere with bacterial communication pathways.

After joining the Whiteley Lab, Kibby delved into research about bacterial immune systems and host-pathogen interactions. In studying the constant conflict between bacteria and phages, Kibby explored the wide range of immune pathways bacteria use to counter phage infection.

Kibby and her research colleagues homed in on proteins containing a NACHT module, which are present not only in prokaryotic bacteria, but in eukaryotic cells as well. These genetic overlaps demonstrate that elements of the human immune system originated in bacteria, Kibby says.

“Rather than NACHT modules evolving out of thin air, it’s more likely they came to us from bacteria,” she explains. “At some point early in the history of human evolution, an ancient eukaryote interacted with a bacterial cell that had evolved this type of immunity and was able to adopt that for its own protection.”

The incredible diversity of bacteria

After four years of research, Kibby and her colleagues published their findings about how these bacterial proteins protect against phage. She then pivoted to research using AlphaFold Multimer to predict protein-protein interactions: “I shifted to this new approach in part because our mammalian NACHT proteins that have this great example of recognizing specific proteins,” Kibby says. “So, I thought I would learn something new and see if I could use computational tools to predict similar interactions in bacteria.”

AlphaFold Multimer is a tool that emerged from Google DeepMind, one of Google’s artificial intelligence think tanks, and has proven extremely good at predicting the structures of proteins from just an amino acid sequence, for example. It also can predict the interactions between multiple different proteins.

After learning the computational underpinnings of these predictions, Kibby is now doing lab work with actual proteins to determine whether the predictions are correct—do the proteins actually do what the computer says they will?

“I hope what we’re doing now helps set a standard for how to integrate protein predictions with wet lab validation,” Kibby says. “AlphaFold Multimer is really just another screening tool. It’s amazing and it’s shattering all the barriers of what we had been able to do before, but you will always have to have your controls and always have to validate your hits.”

In the midst of this research, Kibby hopes to defend her thesis in September and receive her PhD in December. She then aims to do postdoctoral research and ultimately earn a role at a university that allows her to research and teach, because guiding people through the fascinating universe of bacteria is one of her passions.

“The way I explain it is, everything is infected by viruses, and we have evolved number of ways to protect ourselves from these threats,” she says. “A lot of times, we think of bacteria as threats to our own immune system, and that’s true, they can be. But bacteria are also threatened by virus, and just like us, to protect themselves they have also evolved immune systems.

“If you look at CRISPR, for example, it’s revolutionizing medicine and research, but in the wild CRISPR is a bacterial immune system that protects bacteria from phages. There are very practical human applications for understanding the incredible diversity of bacteria.”

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