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Nov. 13, 2003 -- No. 599 |
IBEA, UNC scientists build biologically active genome using improved methods
By DAVID WILLIAMSON
UNC News Services
CHAPEL HILL -- Working together, scientists at the non-profit Institute for Biological Energy Alternatives (IBEA) and the University of North Carolina at Chapel Hill have developed significantly better methods of chemically constructing an artificial but functional genome, the complete set of genes an organism requires to survive and reproduce.
The team’s success was announced at a news conference in Washington, D.C., Thursday (Nov. 13) at the U.S. Department of Energy. Among those presenting details were Secretary of Energy Spencer Abraham, whose agency sponsored the research; Dr. J. Craig Venter, IBEA president; and Dr. Clyde A. Hutchison III, Kenan professor of microbiology at the UNC School of Medicine. A detailed report will appear soon in the Proceedings of the National Academy of Sciences, a professional journal.
"Our successful genome synthesis was for a bacterial virus, or bacteriophage, named Phi X 174," said Hutchison. "The virus has a genome 5,386 base pairs in length. We assembled the complete double-stranded genome from 259 chemically synthesized short pieces of single-stranded DNA known as oligonucleotides."
Researchers used that to produce DNA that they then infected the bacterium E. coli with to produce fully infectious virus particles indistinguishable from naturally occurring ones, he said.
"The important thing about the work is that the methods developed are much easier and faster than previous methods," Hutchison said. "These methods should allow us to synthesize much larger genomes than have been synthesized previously."
Hutchison’s special relationship to the project was that he has worked with Phi X 174 off and on since 1960 when he entered graduate school. The chromosome of that virus was the first DNA molecule to be completely sequenced.
"I was part of the team that accomplished this in the 1970s when I was on sabbatical in Dr. Fred Sanger's laboratory in Cambridge, England," he said. "This virus was also used in the first experiments on site-directed mutagenesis, work I did with Dr. Michael Smith and for which he was awarded a Nobel Prize in 1993. So in the present project, I was the person who understood how to work with the virus because of this previous experience."
The IBEA team, based in Rockville, Md., produced synthetic, multi-gene segments of a genome larger than 5,000 base pairs in just 14 days. Bacteriophages are viruses that infect bacteria and are not harmful to humans, animals or plants.
Authors of the PNAS paper are Dr. Hamilton O. Smith, scientific director of IBEA; Hutchison; Cynthia Pfannkoch of IBEA; and Venter. They chose Phi X for several reasons, Venter said.
"First, working with this bacteriophage poses no health or ethical concerns. Second, Phi X has been well studied in the laboratory, and its genome had already been sequenced. Finally, because of its unique genetic code arrangement, it is very easy to verify whether exact synthesis has occurred."
By making synthetic organisms, researchers hope they can rapidly and effectively harness all energy in the organism toward either energy production, likely in the form of hydrogen, or carbon sequestration, he said.
"Synthesis of Phi X by Ham Smith, Clyde Hutchison and the IBEA team is an important step toward our ultimate goal of synthesizing a complete cellular genome," Venter said. "Work in creating a synthetic chromosome/genome will, at its most basic level, give us a better understanding of the biological process.
"Genome composition, regulatory circuits, signaling pathways and numerous other aspects of organism gene and protein function will be better understood through construction of a synthetic genome," he said. "Not only will this basic research lead to better understanding of these pathways and components in the particular organisms IBEA scientists are working on, but also better understanding of human biology. The ability to construct synthetic genomes may lead to extraordinary advances in our ability to engineer microorganisms for many vital energy and environmental purposes."
The research is a next logical step in trying to understand the key elements that comprise a biological system, Abraham said.
"This is a major goal of the biological research carried on by the nation’s major public and private research organizations -- including the National Science Foundation, the National Institutes of Health and the Department of Energy’s Office of Science," he said. "The Biological and Environmental Research program office of DOE’s Office of Science funds the IBEA research as part of the Genomes to Life program."
The research is consistent with DOE’s mission to explore innovative, efficient, and cost-effective ways to use biology to generate clean sources of energy, remove excess carbon dioxide from the atmosphere and clean up environmental contamination, Abraham said.
Both Abraham and Venter stressed that because the advance also raises the possibility of harmful misuse of the new technology, leaders in the scientific and national security communities are discussing how to maximize scientific progress while satisfying ethical and security concerns.
Examples of possible benefits of synthetic genomics include:
The Institute for Biological Energy Alternatives is a research-based institution dedicated to employing genomics to develop cost-effective biological fuels and other environmentally safe activities.
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Note: Reach Hutchison at (919) 225-7937 (cell), (919) 966-4503 (work) or clyde@email.unc.edu. To reach Venter, call Heather Kowalski at (301) 309-3444.
Contact: David Williamson, (919) 962-8596