Even when she was in college at a small liberal arts school, University of North Carolina Asheville Assistant Professor of Organic and Biochemistry Caitlin McMahon knew she wanted to work as a professor with undergraduate students. “I loved chemistry, science, and research, but I also really loved teaching, mentoring, and working with students,” McMahon says. “So that was always my goal, to do something that combines the two.”
McMahon will be able to maximize those skills and passions thanks to a $377,693, three-year R15 Academic Research Enhancement Award (AREA grant) she received from the National Institutes of Health (NIH), National Institute of General Medical Sciences. It will fund work with undergraduates on her project “Characterization of Bacterial Lectin-Carbohydrate Binding and Development of Anti-Adhesion Inhibitors.”
The NIH grant is undergraduate-driven and will fund five students’ work over the next three summers. “They’ll be doing the bulk of the experimental work,” she says. Students will be trained on these projects and learn a range of topics: organic chemistry, microbiology, molecular biology, biochemistry, as well as gaining skills using advanced instrumentation.
It will also fund one student for two years at Western Carolina University as part of the schools’ collaboration. It will allow UNC Asheville to purchase new equipment that the university does not yet have access to and fund McMahon’s and her students’ travel to conferences to present the results of their work.
McMahon completed her graduate work in organic chemistry at UNC Chapel Hill, before moving to a postdoctoral position at the Massachusetts Institute of Technology. There, she began to apply the use of chemistry to probe biological systems and started to study the role that sugars — or carbohydrates — play in host-bacteria interactions.
A layer of carbohydrates coat cells. When one cell encounters another cell, carbohydrates are the first thing that the cells interact with. That coating has a few purposes: It helps to protect the cell, serves in recognition as a sort of “cellular ID,” and plays a role in adhesion to other cells. Many of the interactions of this carbohydrate layer are mediated by carbohydrate-binding proteins called lectins.
McMahon likens the interaction of lectins to velcro: where one side of a cell sticks to the other side of a different cell. Lectin interactions play roles in things like infections. Bacteria have lectins that bind to or adhere to hosts and then form biofilms — structured collections of bacteria that are harder to treat with antibiotics.
“The goal is to basically stop those interactions from happening to make the bacteria easier to treat,” McMahon says. She aims to find different ways to put what she describes as “tape” on one side of that velcro to keep it from adhering to unwanted cells.
For this grant, McMahon and her team will make and test inhibitors of lectins involved in adhesion in E. coli and H. pylori bacteria, for which no one has yet created effective inhibitors. E. coli is involved in diarrheal illnesses and H. pylori is a common stomach bacterium that can cause ulcers and stomach cancers. H. pylori has multiple lectins, and this work will provide insight to help understand the different roles they may play in infections and disease outcomes.
For her groundbreaking work with this grant, McMahon and her UNC Asheville team will work in collaboration with crystallographer and Associate Professor of Chemistry and Physics at Western Carolina University, Jamie Wallen. The crystal structures he and his team create will allow them to review at a molecular level what interactions cause lectins to recognize and bind carbohydrates.
“They don’t bind just any carbohydrate, they bind specific ones and for specific reasons and that plays an important role in their function,” she says. “Ultimately, we want to mimic that with our molecules that we’re making as inhibitors and increase their ability to stick to those proteins instead.” The better they can design molecules as inhibitors the more likely it is that it could ultimately lead to treatments and or preventions for these bacterial infections.
The strategy of this work is called anti-virulence, or shutting down bacterial weapons and defenses, an alternative to antibiotic treatments. “The goal is to basically make the bacteria easier to treat without killing them,” she explains. “If we can treat the bacteria, make it easier to clear on our own with our own immune systems, then that’s great because we could reduce the use of antibiotics, decreasing the development of resistance to those drugs that are already fastly losing power.”
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