Institute reveals secret life of microbes

Of Earth’s nearly countless species of microbes—bacteria, fungi, viruses, and protozoa—we’ve studied only a few in depth. They can resist stress by congealing into a tough, glassy material. They have observable social behaviors, like sharing public goods. In our own bodies, they outnumber human cells by 10 to one. They affect our health, the economy, and the environment in ways we’re still just beginning to grasp.

“It’s wise to study microbes because they really impact everything we care about,” says Christine Jacobs-Wagner, Ph.D., the William H. Fleming, M.D. Professor of Molecular, Cellular, and Developmental Biology and a Howard Hughes Medical Institute investigator.

Jacobs-Wagner is the director of the Microbial Sciences Institute on Yale’s West Campus. She and four other institute faculty work at the interface of disparate disciplines, studying microbes with tools from computational, life, and physical sciences. Each has a primary appointment at the School of Medicine or the Faculty of Arts and Sciences, and their collaborators outside the institute include geneticists, chemists, ecologists, evolutionary biologists, computational scientists, and engineers.

With its faculty united by a common interest but not by methods or training, the institute flips the traditional concept of the academic department, Jacobs-Wagner says. “In the past, in a department of biochemistry, you would attract people [who] focus on biochemical approaches to address questions on anything,” she says. “We wish to do the opposite ... We address a variety of microbial questions, but they are all microbial questions, and our goal is to attract people with training in various disciplines.”

Not long ago, scientists studying microbes were largely limited to the few species that grow in culture media. But in recent years, as genetic sequencing has grown much more affordable, researchers can sequence the genetic material of hundreds of microbial species from an environmental sample at once, producing vast datasets that give a glimpse of how communities interact with each other and their environments. This technique is called metagenomics. Other tools like bioinformatics and advanced microscopy have also helped to transform microbiology by opening a window on microbial behavior and evolution.

Andrew Goodman, Ph.D., associate professor of microbial pathogenesis, studies the role human-associated microbial communities play in host disease and health. Goodman’s interests include how the beneficial bacteria that live in the intestine—collectively known as the gut microbiome—interact with each other and their host. In 2015 his team reported in Science on a gene that beneficial gut microbes can use to survive host inflammation events, and in a 2016 paper in Proceedings of the National Academy of Sciences uncovered direct warfare between our friendly bacteria. His ongoing research projects are examining a different aspect of host-microbe interaction: his lab is working to understand how our gut microbes could influence the metabolism and function of important medical drugs.

Eduardo A. Groisman, Ph.D., professor of microbial pathogenesis, studies how bacteria adapt to new conditions by adjusting which genes they express. For instance, the gastroenteritis-causing bacteria Salmonella enterica lives inside host immune cells. Groisman’s team found that within those cells, these bacteria produce cellulose—a substance commonly found in plants but that also helps bacteria cling to surfaces in groups—and that as it dials down cellulose production, it becomes more virulent.

This helps explain how Salmonella modulates growth inside host cells. The results appeared in a 2015 article in Proceedings of the National Academy of Sciences.

Biophysicist Alvaro Sanchez, Ph.D., currently a junior fellow at Harvard’s Rowland Institute, studies how microbial communities evolve. A focus of his lab is the evolution of “public goods” production in these communities—for instance, when microbes secrete enzymes that break complex sugars into simple ones. His team assembles and cultures microbial communities, with some microbes engineered to display particular behaviors, then uses mathematical models to study their community dynamics. In a 2013 paper in PLOS Biology, his team described how a population of cooperative, resource-sharing yeast that is invaded by non-contributing “cheaters” can still reach a stable equilibrium—but the community is less able to resist outside stresses. Sanchez will join the faculty of the institute and of Yale’s Department of Ecology and Evolutionary Biology in July.

In Jacobs-Wagner’s lab, bacteria help illuminate how cells self-replicate. “We share an evolutionary link with microbes, so they can be a really fantastic model system to study basic biological function,” Jacobs-Wagner says. For replication to occur, many intricate events have to occur in the right order. Yet bacteria can proliferate very quickly, with some able to divide every 20 minutes—“and it virtually never fails, which means that the system is very robust,” Jacobs-Wagner says. Her lab also explores how bacteria organize their inner components in space.

“Before we started we thought they were just tiny bags of molecules floating around. Our lab has contributed to the [finding] that their cells are actually spatially organized, and that this organization is critical for cellular function and behavior,” Jacobs-Wagner says.

Shocking news: Some bacteria have hairlike projections that conduct electricity. Nikhil Malvankar, Ph.D., the institute’s newest faculty member, is an assistant professor of molecular biophysics and biochemistry who is a physicist by training. As a doctoral student he developed techniques to study materials with “interesting quantum-mechanical properties,” Malvankar says. Then he realized those techniques could be put to a different use.

“Biology is a lot more complex,” Malvankar says. “You can really have a breakthrough if you apply these techniques to biological problems instead of conventional physics problems.” While a postdoctoral fellow at the University of Massachusetts, Malvankar was part of a team that found certain soil-dwelling bacteria sport hairlike protein “wires” called pili that dump excess electrons. That discovery has potential implications for developing bioenergy sources, as well as for understanding how certain infections begin. He was the first to use a technique called electrostatic force microscopy to visualize these electrons traveling along bacterial proteins.

“I’m really excited to be here,” says Malvankar. “It’s an amazing idea, putting all the people working on microbes under one roof.”