Prof. Nicolas Buchler has received the Basil O’Connor Starter Scholar Research Award from the March of Dimes, which consists of $75,000 per year for two years. Buchler, who came to Duke in August 2009 with joint appointments in biology and physics, plans to use the grant to study the evolution of genes that oscillate autonomously in anticipation of periodic changes in environmental factors such as light, temperature, and availability of nutrients. Specifically, he’ll be studying the evolution of circadian clocks in the genetic circuitry of yeast.
Circadian clocks have evolved independently in many different species, which suggests a significant advantage in being able to vary biological functions on a 24-hour schedule. “An ancient circadian clock was just a genetic circuit that could respond to light,” Buchler says. “It seems to be the case that at some point it became advantageous to have an internal oscillator. What was the advantage of ‘learning’ to anticipate—of having an independent oscillator?” Other researchers have recently shown that the dominant feature that favors development of an internal, autonomous oscillator is a “noisy signal”—for example, stormy days and full-moon nights that blur the basic pattern of dark night followed by bright day. “What was the feature of the noise that favored emergence of spontaneous oscillators?” Buchler asks. He hopes to be able to answer his question in his lab using fast-growing, well-understood, genetically modified yeast and a signal that’s analogous to light, but easier to control—the availability of a nutrient called galactose. Circadian clocks in yeast are just one example of the larger issue that fascinates Buchler, which is how single-cell organisms might have evolved to anticipate changes in their environment. In the long run, understanding this could provide insight into the workings of parasites and viruses. It has been shown that microbes are capable of associating changes in their environment, such as heat, with future conditions, such as lack of oxygen. Figuring out how fast they “learn” these correlations could lead to more effective treatments for illnesses caused by parasites and viruses. “Alternatively,” Buchler says, “if single-cell parasites and viruses are incapable of predicting certain signals, we could exploit this Achilles’ heel to design more effective antibiotic or antiviral treatments.” As a biophysicist, Buchler says physics supplies the math and the intellectual framework for his approach. He thinks of the evolving yeast as a system that can be understood using nonlinear dynamics. “The scientific question driving this is biological, but we’re thinking about things quantitatively and physically,” he says.