Fighting the Superbugs: DNS’ Sierra Williams Awarded $457,000 NIH Grant

Assistant Professor of Chemistry Sierra Williams, a member of the faculty of the Department of Natural Sciences of Pitzer and Scripps Colleges (DNS), and her student research team have received a three-year $457,000 grant from the National Institutes of Health (NIH) to develop a new kind of protein-based weapon to fight drug-resistant bacteria.

The project, titled “Developing Imaging Tools to Improve Endolysin Activity,” focuses on a group of proteins known as endolysins, which can destroy bacteria by breaking down their cell walls. Williams’ lab will conduct research to create a fuller picture of these proteins as well as develop a tool to quickly test how well they work.

“The NIH award will support our efforts to engineer improved versions of these proteins and to develop a visual tool that allows us to rapidly measure their efficacy,” said Williams, who joined the DNS in 2021.

Drug-resistant bacteria such as Staphylococcus aureus (or S. aureus) are a growing challenge in hospitals and communities alike. According to a recent report from the Centers for Disease Control and Prevention (CDC), infections caused by these bacteria are on the rise, leading to illnesses such as pneumonia, bloodstream infections, and wound infections that are increasingly difficult to treat.

Commonplace antibiotics—known as “small-molecule drugs” because they are made in the lab and have a low molecular weight—have been the traditional treatment for such infections. But as bacteria have evolved to resist them, Williams and her students see endolysins as an exciting alternative.

“Compared to small-molecule drugs, there are few examples of bacteria that have built up defense mechanisms against endolysins,” she explained. “We think they’re a promising alternative to small-molecule drugs.”

While endolysins hold great potential, scientists still don’t fully understand how they work. Williams said the NIH grant will allow her lab team to fill that knowledge gap and design a testing tool that can quickly measure the protein’s effectiveness as a potential therapeutic.

Williams credits her students for laying the groundwork that helped secure the grant.

“Behind the scenes, students did a tremendous amount of work developing and optimizing experimental protocols,” she said. “They collected the preliminary data that formed the foundation of our proposal.”

Over the next three years, the Williams Lab will pursue two goals: deepening scientific understanding of endolysins and providing meaningful, hands-on research opportunities for undergraduates.

“I want my students to develop critical thinking skills, learn to communicate their work effectively, and collaborate as scientists,” Williams said. “And I want them to gain proficiency in techniques like molecular cloning, small-molecule synthesis, and biochemical assays.”

Williams’ path to chemistry began in high school, where teachers first sparked her interest in the subject. As an undergraduate at Temple University, she discovered a passion for organic chemistry, which, she said, “helped me understand the world on a microscopic level.” Her work included research with Emory University chemist William Wuest, who was interested in making small molecules that can kill drug-resistant bacteria That interest deepened during her doctoral studies at the University of California, Irvine.

“Experiences like that were informative because they helped to inform the kind of research experiences I wanted to pursue,” Williams said. “They also directly inspired the focus of what we do in my lab today.”

Now leading her own lab team, Williams emphasizes collaboration and mentorship as essential to her approach.

“I’ve been fortunate to have incredible mentors—from my undergraduate and graduate advisors and professors to my colleagues today,” she said. “Seeing the impact they have made on my career trajectory has inspired me to want to pay that forward and help my students thrive.”