Graduate researcher helps illuminate intricate details of viral replication

Roma Broadberry.When Roma Broadberry, a graduate student in the Grant Lab, talks about her path into science, it sounds like a story about serendipity.

And sure, there’s some of that at play — she’s been at the right place at the right time with the right training — but that wasn’t really a coincidence. Broadberry’s entrepreneurial spirit and her tenacity are what’s at work.

Now a third-year Ph.D. student in Biophysics at UW–Madison, Broadberry has been at the center of path-breaking research in basic science. Her rotation as a Ph.D. student began with her mentor Tim Grant, a pioneering scientist in the Morgridge Institute’s Rowe Center for Research in Virology who uses cryo-electron microscopy (cryo-EM) to illuminate never-before-seen details of how viruses replicate and spread.

“At those first group meetings, I remember thinking, ‘Wow, there are so many people working on this,’” Broadberry recalls. “The project had been ongoing with numerous members contributing over the years, and I arrived at just the right time.”

Recent Rowe Center work culminated in a 2023 paper in the Proceedings of the National Academy of Sciences (PNAS), with Broadberry named as an author. The lab developed new ways to release viral RNA replication complexes from cells, allowing them to visualize the 12-fold symmetric crown at atomic resolution.

For Broadberry, a protein is a puzzle and she is a puzzle-solving enthusiast. Protein structure is crucial to understanding how a virus replicates and can help identify new targets for drugs and therapeutics. Similarly, there are many neurodegenerative diseases where proteins play a role — such as misfolded proteins in Alzheimer’s and Parkinson’s diseases.

“If we can understand the structure as well as we can, we can improve our medicinal approaches,” Broadberry says. “Cryo has become this incredibly popular, accelerated approach to solve protein structures. I just wanted to jump on that train and get my hands in and see what that’s like. It’s been an incredibly huge learning experience and very successful.”

Broadberry has been in the Grant Lab working to develop cryo-EM methodologies to determine the structure of biomolecules. Prior to joining UW–Madison, she received her undergraduate degree at James Madison University where she studied ubiquitin proteins that form pathways regulating many cellular processes. Her interest was piqued. She was accepted into an NSF Research Experiences for Undergraduates program at Boston University where she explored X-ray crystallography and the world of structural biology.

She began looking for a Ph.D. program and soon learned an undergraduate friend was planning to attend UW–Madison. Chris Berndsen, her PI at James Madison, had received his Ph.D. from UW–Madison and by that fall, Broadberry was in the Grant Lab learning how to process complex viral machinery using cryo-EM.

Her interest in structural biology came at just the right time. What’s widely been called cryo-EM’s “Resolution Revolution” was recognized by the 2017 Nobel Prize for Chemistry awarded to a group of scientists who pioneered the method. Universities and research centers, including UW–Madison and the Morgridge Institute, have since poured resources into massive initiatives to recruit and retain cryo-EM specialists — and house the monstrous, complex cutting-edge microscopes.

“It feels like flying a plane, not that I’ve ever flown a plane,” Broadberry says. “You’re sitting in front of all these computer monitors that are all telling you different things. There are keyboards and joysticks and buttons. It’s very overwhelming. But after enough times ‘driving,’ I have become a lot more comfortable.”

And that’s where the Grant Lab comes in. They’re working to improve the art of sample preparation — including a major cryo-EM bottleneck, the orientation of molecular particles for visualization — as well as computation and processing needs, and much more.

Looking ahead, Broadberry’s excited to spend more time working in the UW–Madison Cryo-EM Research Center during her Ph.D. She’s considering a career in tech commercialization, such as patenting or licensing.

Read the original story on the Morgridge Institute website.