Chemistry faculty member and his students steadily assembling new pieces in puzzle of antibiotic resistance

Paul Cook
Paul Cook
Image Credit: University Communications

Little by little, Paul Cook and his students are breaking down the structure of the pathogenic bacteria that enables resistance to a common antibiotic.

The work is painstaking and the breakthroughs, such as one recently published, come in increments that play out over years — in fact the mindset for Cook, associate professor of chemistry, requires five-year goals. Ultimately, it can take decades to see the research fully applied.

But the benefits are multi-fold, according to Cook. For one, the research is producing important knowledge on thwarting resistance to the antibiotic. Also, academia is what Cook calls a "good niche" for antibiotic resistance studies since the market incentives for pharmaceutical companies to do that research are limited.

And crucially, the opportunity for undergraduate students to learn how to break down proteins in this manner trains them for their future, whether it's in antibiotic resistance research or another area, such as cancer. His work has been done under a National Institutes of Health grant.

"The research is approachable for students," Cook said. "There is the goal of treating antibiotic resistance, and the way the projects can be arranged into manageable chunks is good for undergraduates because they can fit that into their class schedules."

Cook has worked with the antibiotic, fosfomycin, since his time as a post-doctoral research fellow. The drug, approved in the 1970s, is commonly used to treat conditions such as urinary tract infections.

The newest research, recently published in Protein Science sheds more light on the protein structures of the rogue bacteria that combat the effectiveness of the antibiotic. Mary Karpen, professor of chemistry, and Robert Woodward from University of Mount Union also collaborated on the research, Cook said. In addition, two of Cook's students, who both continued on to the medical field, were also on the paper: Chelsea Meloche and Michaela Castleman.

Grand Valley researchers used X-ray crystallography at the Argonne National Laboratory near Chicago to help analyze the protein crystals, providing more crucial foundational information on the bacteria.

Cook and his team placed the information in a public protein data bank that is available to scientists, including those working on antibiotic resistance, Cook said. Understanding the components of that protein will allow medicinal chemists to design a drug to reduce or even eliminate resistance to the antibiotic.

The access Cook's students get to a facility such as the Argonne National Laboratory is rare at the undergraduate level, he said, and a key factor in the comprehensive training the students receive.

That's why though the research arc itself is long, the opportunities for students continually motivate Cook, he said. 

"Growing cells, making protein crystals, modularizing the research, those are things they can do," Cook said. "We're in it for the knowledge and for training students."