This MacArthur ‘Genius’ Has Found a Connection Between Geology and Genetics
WHY YOU SHOULD CARE
Because crossing disciplines yields great insights.
“I was an undergraduate advising nightmare,” Caltech professor Dianne Newman recalls with a smile. She initially planned to major in comparative literature at Stanford. Instead, she settled on German studies — while juggling science and engineering classes — before landing on a Ph.D. in environmental engineering at MIT.
But it’s that intellectual fluidity that lets the newly crowned MacArthur “genius” bring fresh perspectives to our understanding of infectious disease. Newman adapts techniques used to study bacteria from remote environments (like the deep sea), which are hard to grow in the lab, and applies them toward understanding bacteria in chronic infections — marrying her fascination with the old with modern, urgent problems of infectious-disease spread. Most recently, her research on how ancient microbes thrived before Earth’s atmosphere had oxygen has led to investigations into how Pseudomonas aeruginosa, a type of soil bacteria, thrives in the lungs of patients with cystic fibrosis, a genetic disorder that raises the risk of respiratory infections. As it turns out, those two environments have more in common than you might think.
P. aeruginosa bacteria is a nasty problem for cystic fibrosis patients in whose lungs it shows up: It can splinter into subpopulations that don’t respond to antibiotics. Figuring out how that bacteria survives in the host during a chronic infection can inform the treatment of not only cystic fibrosis, but also other chronic respiratory infections and chronic wound infections, common in diabetes. It’s “a big, big target,” says Luanne Hall-Stoodley, a microbiologist at Ohio State University.
Newman’s research is part of the growing field of microbial ecology, which focuses on how bacteria interact with each other and their environment. Parallels are emerging; diabetic wounds have limited oxygen, much like soil. So, scientists posit: Might the way bacteria adapt to oxygen-poor soil apply to the bacteria creeping around diabetic wounds? Traditionally, clinical microbiologists have studied bacteria in test tubes — but that might not reflect the true conditions of the human body. Newman’s peers cite her as a pioneer in modeling physiological environments. She draws from the geosciences to measure key chemical characteristics of the environments the bacteria in our bodies inhabit, so we can constrain how we study them in the lab.
Her work may help us “model better in the lab what’s actually happening in the body.”
Luanne Hall-Stoodley, microbiologist at Ohio State University
Understanding how disease-causing bacteria grow in the body can help us better target them. For instance, P. aeruginosa grows on lung surfaces in layers known as biofilms. Those at the top of the biofilm grow quickly, easily nabbing nutrients; those inside or at the bottom grow slower. Most antibiotics, however, target the fast-growing bacteria. Now, instead of solely growing P. aeruginosa in a test tube, Newman uses geomicrobiology techniques to understand its metabolism as it works on cystic fibrosis patients. Her work may help us “model better in the lab what’s actually happening in the body,” says Hall-Stoodley.
Roberto Kolter, Newman’s former postdoctoral adviser at Harvard Medical School, says this cross-disciplinary thinking comes naturally to her. “People tend to have a very narrow focus,” he says, “but Dianne knows there are no boundaries.” Indeed, she says her college thesis research in Berlin’s Pergamon Museum, translating ancient texts, dovetails with her microbial evolution work. “I’ve always loved history,” she says. “It’s at once very mysterious and alluring and also frustrating, because you can’t go back … You can’t have absolute confidence anything you’re hypothesizing is correct.”
Newman Skypes from her sunlit, buttercup-yellow kitchen. Willowy and bookish, with glasses and gray-flecked curls, she is soft-spoken but voluble. Sometimes “she gets so excited she’s almost on the verge of laughing,” says Jared Leadbetter, a colleague of Newman’s at Caltech. “She brings sort of a lightness.” She recalls her peripatetic childhood — her father was a journalist turned diplomat — which took her throughout Latin America and, finally, to Virginia. She entered school science fairs, encouraged by her dad.
He died while Newman was in college. “One of the promises I made him was that I would go on to grad school in engineering,” she says. So as an undergrad, she conducted materials science and fluid dynamics research to make her a competitive candidate. One day in grad school, Newman identified a mysterious yellow substance in a bottle her lab mate handed her: arsenic trisulfide, produced by bacteria. She published seminal research on how bacteria respire arsenate, turning it into arsenic, a more toxic, mobile form — a problem in places with arsenic-contaminated groundwater, like Bangladesh. Newman also found that a family of proteins that allowed early bacteria to respire arsenate has been conserved throughout evolution. “I was hooked,” she says.
In 1998, Newman began postdoctoral research on bacterial genetics at Harvard Medical School. Only a few months later, Caltech offered her a faculty position, which she started in 2000. There, she dug into her P. aeruginosa research; her lab has discovered that the microbes can generate energy using molecules called phenazines. Off went Newman’s interconnected mind: She wondered whether she would see phenazine in the lungs of cystic fibrosis patients. And she was right: In patients with weak lung function, she found high phenazine concentrations, and, in fact, phenazine concentration also predicted future declines in lung function.
As with most basic research, Newman’s work “doesn’t necessarily mean the cure for Pseudomonas aeruginosa is just around the corner,” Hall-Stoodley says. Still, it’s a crucial step to understanding the diversity of bacterial physiological states that influence how they survive in chronic infections, and persist even despite antibiotic treatment.
And next? Newman has set out to unravel the physiological functions in bacteria that produce molecules called hopanoids, inspired by wanting to better interpret their molecular “fossils” in ancient rocks. Since the community of organisms that interact with plants also includes hopanoid-producing bacteria, she’ll need to dig into plant biology — in which she has no background. But therein she finds the thrill. “No important problem is ever going to be easy,” she says. “These problems are like puzzles.” As with all good puzzles, “it’s very satisfying to crack them.”