Merissa Brousseau, an IPiB graduate student, will be defending her Ph.D. research on August 15, 2024. Her research in the Henzler-Wildman Lab investigated the mechanisms responsible for regulating a multi-drug efflux pump in bacteria.
The EmrE pump, when coupled with two protons, shifts its orientation to transport antibiotics across the bacterial membrane. Scientists have been investigating how this shift occurs in the hopes of more effectively treating bacteria with antibiotics by preventing cells from pumping medication out. Researchers in the Henzler-Wildman Lab previously identified that the tail end of EmrE may play a role in regulating the protein’s activity. Brousseau explored the role of the protein’s tail further.
By engineering the protein to remove its tail and generate modified versions of the tail, then using NMR and biochemical assays to identify how its function differed from the wildtype, Brousseau confirmed that EmrE’s tail acts as a gatekeeper. When a drug binds to EmrE and interacts with EmrE’s tail, the tail’s position shifts, allowing protons to release and EmrE to change its orientation.
“These findings are really exciting, and good news for humans,” says Brousseau. “When we treat with antibiotics, we don’t want the bacteria to transport the drugs out of the cell. The tail on EmrE — and in other proteins in the same class — is a new potential target. Understanding more about how the tail acts as a gatekeeper could allow us to exploit it. Depleting bacteria’s energy sources by forcing protons to leak out could be a way to weaken infectious bacteria and even improve the effectiveness of existing antibiotics.”
After graduating, Brousseau is excited to continue her exploration of EmrE as a postdoctoral researcher in the Henzler-Wildman Lab. Brousseau is also happy to have more time in Madison, where she found a strong community of endurance athletes. Her marathon and triathlon training helped Brousseau stay focused and motivated in her graduate research. She is proud to have completed 10 marathons and many triathlons, including Wisconsin’s Ironman, during graduate school.
“There are a ton of opportunities to explore outdoors in the Madison area,” says Brousseau. “I moved here from the Boston area, and I like road biking here much more. It’s so fun being able to go a couple of miles in any direction and not spend so much time sitting at traffic lights. It’s a great way to explore.”
To learn more about Brousseau’s research, attend her Ph.D. defense, “Investigating allosteric regulation of the multi-drug efflux pump EmrE” on Thursday, August 15 at 2:00 p.m. CT in Room 1211 of Hector F. DeLuca Biochemical Sciences Building.