For the last half century, biological researchers have looked at one gene and its related protein in isolation from others. Although the take-home message from this approach is that biology and medicine are complex, “we still don't understand deep principles,” says Leroy Hood, M.D., Ph.D., president and co-founder of the nonprofit Institute for Systems Biology (ISB; www.systemsbiology.com) in Seattle.
Dr. Hood defines systems biology as the science of discovering, modeling, understanding, and ultimately engineering at the molecular level the dynamic relationships among biological molecules that define living organisms. A “system” can be any particular aspect of an organism’s behavior that a researcher wants to consider as interrelated. Whatever the chosen system, researchers define its fundamental elements and the interrelated biological networks and their dynamics. Not only do they look at the networks directly that encode the particular system of interest, but they also see how all the networks interact. “Through an integration of these factors, we come to understand the system’s properties,” Dr. Hood explains.
Fourteen years ago Dr. Hood headed the department of molecular biotechnology at the University of Washington, funded by Bill Gates. That endeavor, the first cross-disciplinary department in the world, integrated physical, biological, and computational scientists in the field of interdisciplinary biology.
“We learned each other’s language and created the fundamental framework used at ISB,” says Dr. Hood. Now ISB uses this cross-disciplinary environment to focus on selected biological and medical problems. Designed along academic lines, ISB develops new technologies and computational tools to promote systems biology, trains young scientists, and spins off intellectual property and startup companies.
Several scientific themes are emphasized at ISB. One focuses on microorganisms, such as yeast and halobacterium, as model organisms to drive the development of new quantitative technologies. “We’re putting the major effort into microfluidics and nanotechnology devices for making in vitro measurements,” says Dr. Hood.
The microbial experiments also help to drive the development of computational tools for analyzing large amounts of data. “We’re pushing the frontiers of computational and mathematical techniques,” Dr. Hood adds. Innate immunity, such as the responses of toll-like receptors to foreign microbes, form another research focus at ISB. Yet another focus is the application of systems biology to medicine and human diseases, particularly prostate cancer and prion diseases.
The project with halobacterium illustrates how a systems biology approach unlocks biological mysteries. Just seven years ago, little was known about halobacterium, a microbe that gives the Great Salt Lake and Dead Sea their yellow-orange color. ISB scientists sequenced the entire genome of halobacterium, then generated detailed information sets about its genomics, proteomics, and biological circuitry.
Halobacterium thrives in high salt concentrations, withstands high levels of radioactivity, and efficiently converts sunlight into energy. The microbe is ideally suited to be genetically engineered to solve bioremediation problems or create biologically energetic compounds.