Volume 3, Issue 21 June 2006
Start Your Protein Engines
George Oster is also a professor with the College of Natural Resources' Department of Environmental Science, Policy & Management.
In the world of hot rods, UC Berkeley professor George Oster would be considered a "motorhead." He knows the ins-and-outs of motor mechanics, from stroke cycles and rotary processes to thermodynamics and fuel efficiencies. But the motors he studies aren't new souped-up engines built for today's automobiles. Oster, a professor of cell and developmental biology, examines the biological nanomachines that propel bacteria through our world and pack DNA into viruses against incredible pressures.
Oster and his research group investigate the physics and chemistry behind great engineering mysteries of the natural world, from protein motors to cell motility to how bacteria form thriving populations that aren't so different from ant colonies, or even human societies.
"It's like figuring out how people walk and then putting them in a football stadium to see how they behave in a crowd," says Oster, also a faculty affiliate in the California Institute for Quantitative Biomedical Research (QB3) and a professor of mathematical ecology. "But we always start with the physics, like how do they move in the first place?"
For several years, Oster has addressed fundamental questions about protein motors, identifying their energy sources and uncovering how that energy is converted into mechanical forces.
"We have to combine structural biology, biochemistry, thermodynamics, mutation studies, and other lines of inquiry and then synthesize all of it into a mathematical model," Oster says. "That model has to both fit with existing experiments and also suggest new experiments to do."
A computer-generated model of the structure of ATP synthase, including the two motors (marked here as F0 and F1).
For example, in recent years Oster and his colleagues created a groundbreaking model of ATP synthase, an enzyme that synthesizes ATP, the universal fuel molecule that powers all cells. ATP synthase is essentially a factory built around two rotary motors. One of the motors forces the other to rotate as a generator that cranks out ATP. Oster's contribution was in showing how the two motors generate their torque from very different fuel sources.
The first motor is essentially electric. It's powered, Oster explains, by a transmembrane electro-chemical potential that drives the flow of ions across the cellular membrane. The other motor is powered by ATP, the same substance that the enzyme produces.
Of course, ATP synthase is only one of nature's many protein motor systems. Working with UC Berkeley professor Carlos Bustamante, researchers have also studied the motor that packs a virus's DNA so tightly that it can be injected into a hijacked cell at ten times the pressure of a cork shooting out of a champagne bottle. And they've modeled the donut-shaped molecular motors that move along DNA strands during replication.
The biomolecular portal motor of bacteriophage PHI-29 (yellow) compresses the coiled DNA into the viral capsid at 6,000 times its normal pressure. (courtesy the Bustamante group)
"The cylinders all operate in sequence like an old-fashioned airplane motor," Oster says.
As the researchers better understand how, say, bacteria propel themselves, they're also investigating where the organisms' motility takes them. When hundreds of thousands gather together, Oster says, they can signal each other to "self-organize into elaborate structures that are symmetrical and beautiful," while also serving a biological purpose. But what are those rules of higher-level organization? And what might they tell us about higher-level organisms that coordinate their own collective activities?
It's these kinds of nested puzzles that keep Oster fascinated, he says.
"No model is final and all models are wrong in some detail or other," he says. "So we're always revisiting old models and patching them up or throwing them out and making new ones. You don't want to get too attached to your models."