As a child growing up in Belgium, Christine Jacobs-Wagner demonstrated an intense determination at an early age. "My mother tells me that when I was very young I swam the length of a 25-meter pool. I couldn't really swim but I wanted to get the ribbon for doing it. So I just did it. It was just pure will, no style," she says laughing. Since then she's learned to swim—well enough to take up high-speed kite boarding. "You don't need waves, and it's much, much faster than windsurfing."
She remained focused on sports through high school, but math, biology, and chemistry started to pique her interest too. "I knew I didn't want to be a professional athlete, so when I went to college I chose between law, engineering, and biochemistry." Once she started learning biochemistry, she was quickly hooked. Now she turns the steely determination she developed in sports to her research, refusing to be limited by practical matters or difficult problems that confront her in a relatively young field that studies the internal organization of bacteria. "We have great fun asking the questions that challenge us the most," says the Yale University microbiologist.
In doing so, Jacobs-Wagner has revealed textbook-changing details about cell cycle control and cellular structure in bacteria. It turns out that despite their small size, bacteria are more like higher organisms than was once thought.
Scientists used to view bacteria as miniature bags of randomly distributed chemicals. Today's high-resolution light microscopes and digital cameras have helped Jacobs-Wagner and others to prove otherwise. These single-celled organisms have a well-organized internal structure that controls signaling within the cell, the movement of proteins, and even cell division. "It is not a deserted land. It is a highly organized city, with buildings and highways," she says.
As a postdoctoral fellow at Stanford University, Jacobs-Wagner labeled a signaling protein with a fluorescent tag and found that the bacteria tightly corralled the protein to a narrow part of the cell. "To our huge surprise, the protein localized to a pole," she says. "We had not anticipated spatial regulation in bacteria." After the publication of that discovery in 1999, scientists immediately started searching for the mechanisms bacteria use to build and maintain that internal organization.
In a 2003 study of Caulobacter crescentus, Jacobs-Wagner and her colleagues discovered a cytoskeletal protein, which they called crescentin, that is required for the bacterium's striking crescent shape. It is similar in structure and function to eukaryotic intermediate filaments, whose elasticity and toughness help cells maintain their structure.
Jacobs-Wagner and her research group next described how polarity is reset from one generation to the next. They uncovered a protein used by C. crescentus to distinguish one tip from the other. As the bacteria prepare for division, a protein called TipN is transported to the center of the cell. When the mother cell splits, TipN is automatically concentrated at the new poles of each daughter cell. C. crescentus uses TipN as a molecular landmark to ensure the correct polarity in daughter cells as it prepares for a new round of cell division. When the researchers engineered bacterial cells that lacked TipN, cell division was disorganized and the population lost its homogeneous nature. She went further and showed that even seemingly symmetrical bacteria use asymmetric protein localization to control the cell cycle.
Just as eukaryotic cell biology moved from descriptive work to quantitative measurements, Jacobs-Wagner says, ready or not it's time to push bacterial cell biology in that direction. "I think this is the next logical thing for us to do," she says. "Our strategy is to identify and characterize all components involved, to develop creative methods for addressing challenging questions, and to help transform prokaryotic cell biology into a quantitative science." Her ultimate goal is to build a mathematical model that accurately describes how C. crescentus maintains its spatial and temporal organization. That means pushing the resolution of light microscopy even further. With that in mind, Jacobs-Wagner has already started building the collaborations and gathering the tools necessary to meet the challenge.