In fight against Crohn's, professor battles bacteria

WILMINGTON, Del. — Catherine Grimes is still in her 30s, but she is already a veteran in the war on harmful bacteria.

Having helped design new antibiotics while a graduate student at Princeton University, the New Jersey-native went on to study how those drugs work while earning her doctorate from Harvard.

Now she is researching how the human body fights bacteria on its own, in the hopes of finding better weapons in the battle against Crohn's disease, rheumatoid arthritis and other significant health problems.

"You need to know who your enemy is before you decide how you're going to shoot them down," said the third-year assistant professor of biochemistry at the University of Delaware. "That's what we're doing here in the lab. We're identifying new targets."

Grimes' work has attracted attention from some major independent funding sources. She was named a scholar in biomedical sciences by The Pew Charitable Trusts in 2014, an elite honor that comes with a $240,000, four-year grant. Last month, she also received a $75,000 Cottrell Scholar Award from Research Corporation for Science Advancement and was one of three early-career researchers to receive a $45,000 Strategic Initiative Grant from the university.

Klaus Theopold, who chaired the university's chemistry and biochemistry department when Grimes was hired, called her one of its rising stars.

"She is the newest hire in our department, so it makes it all the more exciting that she's getting this recognition already," he said. "These grants are a major show of confidence in what she's trying to do."

Using an interdisciplinary approach that pulls from chemistry, biology and immunology, Grimes' innovative research is examining how the body identifies bacteria and why it sometimes mistakes beneficial microbes for an invading horde. That research is specifically focused on the building blocks of bacterial cell walls, called peptidoglycan.

"Peptidoglycan is like a jacket that all bacteria wear," Grimes explained. "Humans cells don't have them, so it provides a great way for our immune system to identify bacteria, which in turn determines how it should respond to them."

In other words, bacteria wear uniforms that help the body figure out whether they are friend or foe. Except the body doesn't look for bacterial cells wearing those uniforms. Instead, it looks for fragments of those jackets left behind on the battlefield.

And with 100 trillion microbes in the human body — collectively weighing 2 to 5 pounds — the immune system sometimes has problems keeping all those scraps straight.

At least that's Grimes' working theory.

"We know a little about how this process works, but not a lot," she said. "For instance, it's not completely understood how the jacket gets torn into pieces, how the immune system identifies those pieces or why it might get confused."

Grimes and her team of a dozen graduate students believe they have found a way to place markers on bacterial cell walls that will allow them to identify exactly where the fragments originated, as well as valuable clues about how they got torn off in the first place.

"It could be a combination of bacteria enzymes and human enzymes, but we don't know all the enzymes and we don't know all the fragments," Grimes said. "Our idea is that each different type of bacteria has a different way of ripping apart its jacket. There might be some commonalities, but our hypothesis is that each one does it a little differently and that's how our body tells the difference between good bacteria and bad bacteria."

The body's confusion over "good" bacteria that aid in digestion and pathogenic bacteria that cause infection is believed to be what causes Crohn's disease, a painful inflammatory bowel syndrome that affects as many as 700,000 Americans, mostly between the ages of 15 and 35.

"Our goal is to identify new targets and then screen for new inhibitors, whether that's finding enzymes to break these confusing fragments down or modifying the cell wall before it becomes fragmented," Grimes said. "Ideally, we'll be able to explain how this process of identifying or misidentifying bacteria works, and how we can intervene in that process so you can shut down the bad fragments. And then, hopefully, that research will help a pharmaceutical company develop new antibiotics and anti-inflammatory targets."