CONSIDERING HOW WELL STUDIED THEY ARE, SOME LARGE GAPS remain in our scientific understanding of bacteria. For instance, we don’t yet know how bacterial chromosomes are separated into daughter cells during cell division or how their complicated chemical language really works. Using techniques from a broad spectrum of fields—including biochemistry, genetics, materials science and engineering—biochemistry professor Doug Weibel is designing advanced microtools and novel experimental setups to answer, for the first time, persisting questions about these surprisingly complex microorganisms. Through this basic work, he’s finding novel antibiotics and other interesting drug candidates.
Why are there still so many major unknowns about bacteria? How can that be?
The issue with bacteria is they are so small. By comparison, eukaryotic cells are enormous! For a calibration point, a human hair is about 100 microns in diameter. That’s about the thickness of a piece of scotch tape. And a eukaryote—when it’s spread on a surface—is maybe 40 microns in diameter. But the bacteria we look at are about one micron long, and their short axis is just several hundred nanometers. Until recently it was very difficult to look at them under a microscope and see anything useful going on inside the cell. Fortunately, there’s been a revolution in optical microscopy techniques over the last five years, and now we can see inside them with pretty good resolution.
How has our understanding about these microorganisms grown in recent years?
Historically, bacteria have always been thought of in the context of the way that we studied them: as individuals. They were always freely suspended in liquid nutrients and were dilute enough so that they never made physical contact with each other. But it’s pretty clear now that many bacteria in the ecosystem exist in tight-knit communities.
And during certain developmental stages, bacterial cells will display collective dynamics, where they are no longer acting as individual cells—as little one-bit processors—but are actually making collective decisions. In these cases, they are communicating and acting more like a multicellular organism—as something a lot more sophisticated than we’ve ever really appreciated.
Tell me more about this collective behavior.
A lot of people know that bacteria swim in solution, but they also swim in groups on surfaces. This collective movement on surfaces is called swarming.
As the bacterial community moves across a surface, the cells mix—and this mixing ensures that all of the cells get nutrients and growth factors to continue replicating. Swarming allows the cells to grow explosively and to colonize whatever niche they’re provided with.
What are you trying to learn about swarming in your lab?
We’re trying to figure out two things. One has to do with behavior: How does the motion of individual cells on a small scale lead to the pattern formation—the continuous mixing—of the swarm on a large scale? The other question is really the biochemistry of how it works. How do cells sense the surface and then change their morphology to interact with it?
This work should tell us some basic rules about how cells sense things outside of themselves—from fluids to surfaces to other cells. I think this is super interesting.
Can you describe one of the microtools you’ve developed to study bacteria?
Sure, but let me give you some more context first. In addition to studying the physical interactions between bacteria during swarming, we’re also interested in the role that chemical communication plays in the development of swarms. And swarming is just an early stage of biofilm development, so we are also interested in biofilms, which are basically bacterial communities that are firmly attached to surfaces.
One question that’s been in the field for a long time is, what is the length scale over which these chemical signals can be propagated? That is, if you have a swarm or a small early-stage biofilm that’s secreting signals, how far away does another biofilm have to be before it can no longer eavesdrop? To answer this question we created a microtool that we call the waffle.