Jonathan Rueffer | Science Editor
On Sept. 11, the biology department invited Randy Stockbridge, an associate professor and researcher at the University of Michigan, to present her research to Wooster students. The talk was part of The College of Wooster’s Life Science Seminar series, where guest academics and researchers give presentations on their work.
Stockbridge’s presentation, titled “Ancient stress responses in the modern world: how bacteria co-opt membrane exporters to deal with novel chemical threats,” discussed how bacteria have adapted to harmful human-introduced substances in the environment, namely antiseptics like Lysol.
Randy Stockbridge graduated from Princeton University with an A.B. in Molecular Biology and received her Ph.D. in Biochemistry and Biophysics in 2010 from the University of North Carolina at Chapel Hill. She started her own lab, the Stockbridge lab, at the University of Michigan in 2016, where she works with postdoctoral and graduate students to research how microbes respond to chemical sensors. The lab’s work provides a foundation for new bioengineering approaches to mitigate environmental contamination.
Her presentation at the College opened with a history of how harmful substances were introduced into the environment. In the 1930s, quaternary ammonium cations (Qacs) were introduced as hospital disinfectants. In 1945, Grand Rapids, Michigan — Stockbridge’s hometown — became the first municipality to fluoridate its water supply as part of a National Institutes of Health (NIH) study. In 1995, metformin was introduced in the U.S. as an antidiabetic drug and is now one of the most prescribed medications nationwide. Stockbridge mentioned the effects of exposing the human biome to these new-to-nature compounds. Charlie Cuttino ’26, a biochemistry and molecular biology major, said “It was interesting to learn about how the oral microbiome can develop resistance to fluoride.”
For her research, Stockbridge focused on the molecular basis of exporting Lysol. Lysol export is done via Small Multidrug Resistance (SMR) transporters, which are nature’s minimalist transporters, making the proteins ideal for her research. Stockbridge points to these transports as an example of ongoing evolution, since bacteria co-opt them in metformin degradation pathways. We see the emergence of a new metabolism to break down this new drug that did not have a designated pathway.
Her research focused on identifying the structure of the two major families of SMR transporters: drug exporters (EmrE) and guanidinium exporters (Gdx-Clo). The scientific tools and techniques included X-ray crystal structure determination and monobodies (synthetic binding proteins). Her lab found that EmrE and Gdx-Clo have similar backbone architectures, and that even though the binding site residues are conserved, the hydrogen bond network is not, as Gdx-Clo’s is organized and EmrE’s is chaotic.
Her presentation then shifted to discussing the causes of the promiscuity of these transporters, i.e. how the protein can move structurally-diverse molecules across the cell membrane rather than being highly specialized to a single substrate. With help from lab team members, she found that seven mutations convert a specific Gdx into a promiscuous transporter. However, she wanted to know if all seven mutations were necessary. Instead of testing all 128 different ways to add seven mutations (which would take a lot of lab work), she opted to create a Gibson assembly. This molecular cloning method seamlessly joins multiple DNA fragments with overlapping sequences to create a combinatorial library. They found that a minimal combination of mutation clusters is possible, and that the reaction gets faster with more clusters combined.
The presentation ended with a summary of the key takeaways: SMR transporters have spread among bacteria globally because of selective pressure from antiseptics, and they have a hidden structure that allows access to the membrane for Qacs with alkyl tails. Stockbridge thanked the hard work that her lab members contributed to this research and promoted the University of Michigan graduate program. This was followed by questions from students and faculty, who were interested in hypothetical speculations and specifics regarding her procedure.
“I am beyond grateful I was able to have the opportunity to listen to her advice and research!” said Cuttino ’26.