Washington University in St. Louis leads group studying aging process

September 16, 2004

A research team of biologists and engineers led by faculty at Washington University in St. Louis is seeking to find the Fountain of Youth - not in Florida, but in photosynthetic cyanobacteria (ancient little blue-green algae). Looking at the cellular systems in cyanobacteria, and then in a model plant and a moss species, these researchers want to determine how these organisms protect themselves from radicals, which are chemical culprits in the aging process in everything from bacteria to human beings.

Himadri Pakrasi, Ph.D., Washington University professor of biology, is the principal investigator of a five-year, five million dollar project from the Frontiers in Integrative Biological Research (FIBR) program at the National Science Foundation (NSF). In this project, a team of interdisciplinary researchers plans to use a systems biology approach to delineate the genes and proteins in photosynthetic organisms such as cyanobacteria and plants and model the system these organisms use to cope with radicals. These are products of oxidation and reduction (redox) processes, and are key culprits causing cellular aging.

Cyanobacteria are organisms that gave rise to chloroplasts, the oxygen factory in plant cells. A half billion years ago cyanobacteria predated more complex organisms like multi-cellular plants and functioned in a world where the oxygen level of the biosphere was much less than it is today. Over its very long life span, cyanobacteria has evolved a system to survive a gradually increasing oxidizing environment, which is why Pakrasi and his group want to study the organism so closely.

"The basic goal of the project is to model the networks that cyanobacteria, a model vascular plant called Arabidopsis, and the non-vascular moss Physcomitrella use to handle this chemical environment," said Pakrasi. "We're approaching this in a systematic way, using global genome-based information on all three organisms. We've recruited colleagues outside our area to assist in tackling the project. This kind of interdisciplinary approach is exemplary of the 'New Biology.'"

Both cyanobacteria and Arabidopsis have been fully sequenced and there are imminent plans for the sequencing of the moss Physcomitrella. The grant that Pakrasi and his colleagues received is from a new NSF program called FIBR (Frontiers in Integrative Biological Research). Begun in 2002, FIBR stresses the integrative approach to studying biology, linking the disciplines of systems and computer science - bioinformatics -- with genetics and molecular biology - genomics. The FIBR program is removing the limits biologists have found increasingly frustrating in recent years when seeking funding and finding they can't continue research because they've hit a technological barrier they can't cross.

Pakrasi and his collaborators first obtained a NSF $50, 000 planning grant in 2003 to explore the topic and provide a seminar to delineate the problem and develop a plan. In 2004, they then drew up a proposal to NSF, one of 100 proposals the FIBR program considered. Washington University is one of six institutions to receive FIBR funding this year.

Team members of "A Systems Approach to Study Redox Regulation of Functions of Photosynthetic Organisms," include: Rajeev Aurora, Ph.D., of St. Louis University; Kenneth D. Belanger, Ph.D., professor of biology at Colgate University; Bijoy Ghosh, Ph.D., Washington University professor of electrical & systems engineering; and Ralph S. Quatrano, Ph.D., Spencer T. Olin Professor and Washington University biology chair.Pakrasi and Quatrano are Fellows of the American Association for the Advancement of Science.

Senior investigators are: Richard D. Smith, Ph.D., of the Pacific Northwest National Laboratories; Yukako Hihara, Ph.D., of Saitama University in Japan; and Victoria May, director of the Washington University Science Outreach Program.

A major component of the grant is education. It will extend to St. Louis area high schools via the Washington University Science Outreach program, which keeps K-12 teachers and students up to date in science and engineering trends. Undergraduate, graduate and post-doctoral researchers will get hands-on experiences with the "New Biology," which today is comprised of a good dose of mathematical, statistical and computational skills.

"Associated with this approach is a huge deluge of data," Pakrasi explained. "Few biologists today are prepared to handle that, yet we can't escape it. We give our students lots of biology and chemistry, but in most instances our biology students are not taking that much math or statistics. In the future our students will have to learn these areas. The FIBR grant provides excellent opportunities to embark into this new frontier."

"They don't know biology, and we don't know the computational tools they use, so now we'll bring them together," Pakrasi said, of collaborating with engineers. "We've learned from before our planning grant experience that there are many talented people in engineering who want to know biology, and vice versa with biologists. It's a big challenge, but the novelty is a lot of fun." Pakrasi said the first move will be to model the system in cyanobacteria and then extend it to plants to see how much of the system has been conserved.

"Whatever knowledge we gain from plants may well transcend plant biology to human biology," said Pakrasi. "Plants make all sorts of vitamins, the antioxidant ones, A and E, to protect themselves against oxidants. We will extend what we find to all aspects of cell function. The proteins and enzymes in these protective pathways already are drawing interest from drug companies as targets for new therapies."

Washington University in St. Louis

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