Imagine using the principles of air traffic control to unlock the mystery of why animal cells grow.
Or how about applying the laws of genetics to solve problems in computer circuitry.
Who would fund such innovative, futuristic research?
Answer: the Department of Defense.
This summer, the Defense Advanced Research Projects Agency (DARPA) awarded Stanford nearly $5.3 million to create an unusual consortium of engineers and biologists to study how living cells communicate and develop. The goal is to help biologists resolve fundamental questions about how genes function, while providing engineers a unique biological model for designing intricate electronic circuits.
"It's a very far-sighted project," says Harley McAdams, principal investigator of the three-year DARPA program.
"We have a team of 10 Stanford faculty who are leaders in their respective fields and have demonstrated a capacity for collaborative research," he adds.
McAdams exemplifies the interdisciplinary nature of the DARPA project. A physicist by training, McAdams worked in the high-tech industry before switching to the field of genetics. He is currently a senior scientist in the Department of Developmental Biology in the School of Medicine.
The other nine project members are professors from such diverse departments as electrical engineering, chemistry, genetics - and even aeronautics and astronautics.
"We have an opportunity to look at cellular regulation in a broader context than has been done in the past," notes McAdams, "because we're integrating biological research with advances in other disciplines, such as computation and engineering."
He points out that a major objective is to develop new instrumentation capable of analyzing the extremely complex world of cell division and growth using four different organisms: zebrafish, fruit flies, Streptomyces fungi and the Caulobacter bacterium.
"In essence," says McAdams, "we are working toward determining how every gene affects the quantitative activity of every other gene in each species. We believe the methods and insights developed by electrical engineers involved in electronic circuit design and control theory will be applicable to these genetic networks as well.
"Furthermore," he adds, "there are matters at the frontier of electrical engineering research that relate to problems that evidently have been solved by biological systems, such as the design of circuits with many coupled, nested regulatory loops."
One novel aspect of the DARPA grant will be an attempt to use air traffic control theory to create a mathematical model for understanding intra- and intercellular communication.
"Biological systems are very complex," observes Claire J. Tomlin, assistant professor of aeronautics and astronautics.
As one of the 10 DARPA researchers, Tomlin will use her expertise in air traffic control systems to simulate genetic regulatory networks in cells.
"We are working on a mathematical model to represent and analyze numerous aircraft taking off and landing simultaneously," she says. "We can apply a similar model based on mathematical principles to various biological activities. For example, we'll be looking at the mechanisms by which cells grow and divide, how genes switch different proteins on and off, and how one cell communicates with another."
Tomlin also will examine how these complicated biological systems apply to electrical engineering.
"This is one the most interesting and exciting projects I'm working on right now," she says.
Another objective of the DARPA project, says McAdams, is to develop new technologies capable of rapidly analyzing the function of thousands of genes simultaneously. Researchers will use robotic microinjection, high-speed automated microscopy and other innovative techniques that McAdams predicts "could completely change the way biological research is done."
The robotic microinjection effort is spearheaded by Matthew Scott, a professor of developmental biology, and Olav Solgaard, an assistant professor of electrical engineering.
"Basically, we're trying to make a lab on a chip," says Solgaard. "We want to be able to inject minute amounts of drugs into a fruit fly embryo and measure, manipulate and control its development.
"We want to miniaturize everything," he points out. "Maybe we'll end up one day with a hospital on a chip that can be used to treat soldiers in the field."
Solgaard says he is "excited but cautious" about collaborating with biologists.
"It's all very new to me," says the engineer.
One of DARPA's goals is to encourage people in the early stages of their careers to think beyond the boundaries of their own disciplines.
"Right now, biologists don't understand engineering, and engineers don't understand biology," McAdams observes. "It's a clash of two cultures."
In the grant proposal submitted to DARPA last year, McAdams singled out Stanford's leading role in tearing down academic barriers that often divide chemists, physicists, biologists, computer scientists, engineers and other researchers. He specifically pointed to the Bio-X program created in 1999 through a $150 million endowment from Jim Clark, a former professor of electrical engineering.
McAdams wrote that, thanks to Bio-X, "faculty positions that cross boundaries that were unheard of a few years ago are now routinely accepted," and added that "there is now institutional support for multidisciplinary research and integration of the biological sciences and engineering at the highest levels in the Stanford administration."
Tomlin says that she was drawn to the DARPA project because of her interest in Bio-X - a sentiment shared by Lucy Shapiro, a Bio-X co-founder who is also a co-investigator on the DARPA project.
"The DARPA project is terrific," says Shapiro, a professor of developmental biology, "because it's Bio-X personified."
The Defense Department established DARPA in 1958 in response to the Soviet Union's launching of Sputnik, the first satellite sent into outer space.
DARPA says its mission since then "has been to assure that the U.S. maintains a lead in applying state-of-the-art technology for military capabilities and to prevent technological surprise from adversaries."
The Stanford grant was awarded under a new DARPA program called Fundamental Research at the [Bio:Info:Micro] Interface. Its mission is to create interdisciplinary teams drawn from the fields of biology, information technology and microsystems technology to develop what the agency calls "imaginative, innovative and often high-risk research ideas."
According to the Defense Department, "DARPA believes that revolutionary solutions to important science and technology problems are likely to emerge from scientists and engineers who are working at the frontiers of their respective disciplines. DARPA further believes that biology is now particularly well poised to contribute to advances in other disciplines and to benefit substantially from interactions with those disciplines."
McAdams agrees, noting that "it is very important in the long run that we're developing a new generation of students and postdocs who are multi-cultural - engineers and biologists who are integrated in their thought process."
DARPA's grant to Stanford, which totals $5.265 million, extends from now until Sept. 30, 2003.
In addition to McAdams, Tomlin, Solgaard, Scott and Shapiro, the other five DARPA collaborators are Professors James S. Harris and Martin Morf, electrical engineering; W. E. Moerner, chemistry; Stephen J. Smith, molecular and cellular physiology; and Stanley N. Cohen, genetics.
By Mark Shwartz