Fellow Focus: June Round

July 30, 2011
Friend or Foe? JCC fellow June Round uncovers how our immune system recognizes gut bacteria as harmless—or not.

At first, nothing about the blue, green, and black microscopy image appears remarkable, but upon closer inspection, something emerges—something that hints at a much bigger story. “It wasn’t what we were looking for,” says JCC fellow June Round.

The image shows fluorescent labeled gut bacteria deep within the intestinal crypts of a mouse—not merely in the spacious lumen where most microbes reside. “The closeness of this association highlights that an active communication is occurring between the bacteria and their host,” says Round. But what sort of communication?

It’s a question that has been part of Round’s research since 2007, when she joined Sarkis Mazmanian’s California Institute of Technology lab to pursue her interests in immunology and microbes.

“Within the gut, there are tons of immune cell types waiting to attack pathogens,” she explains. But we live in harmony with many beneficial bugs. How does our immune system know the difference? She set out to answer this question by studying a common friendly gut bacterium, Bacteroides fragilis.

Round’s work hinges on a sugar molecule known as polysaccharide A (PSA), made by B. fragilis and found on its capsule surface. Early in her postdoc, Round found that PSA is integral to gut health. Without it, mice develop inflammatory bowel disease, often a debilitating precursor to colon cancer.

But replacing PSA cured the problem. She published the results in a 2008 Nature paper.

Next, she began a series of experiments to sort out the molecular mechanism behind this host-microbe interaction. She found that one set of immune cells recognized the sugar molecule and suppressed additional immune cells from mounting an attack against B. fragilis. If she removed the sugar molecule, the immune system attacked the friendly bacteria. If she removed the immune cell’s receptors that recognize the sugar molecule, the immune system attacked.

And, if she removed the first set of immune cells themselves, the immune system attacked.
The bacteria had not changed, but the immune system could no longer recognize them as harmless.

For scientists in the field,
the stunning result was in the details. The type of receptor that recognizes PSA is known as a toll-like receptor. Until Round published her research, toll-like receptors were only known to launch an attack against harmful bacteria. But her work showed that the receptors could also induce a regulatory response, essentially turning off an inflammatory reaction. The

results appear in a 2011 Science paper.

Round says that one of her biggest challenges throughout the work was not related to the research itself. Instead, she had to work especially hard to be successful while raising her
two children, ages six and two. She’s grateful that the JCC offered a childcare stipend so that she could afford daycare and live close to lab, enabling her to frequently go back and forth between home and work. Her efforts have paid off. Now, she is moving on from her postdoctoral fellowship to join the faculty at the University of Utah.