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Synthetic Biology: The Real Thing

Boston —At last month's sold-out First International Meeting on Synthetic Biology* at MIT, engineers and researchers discussed exciting progress in creating a "library" of biological parts that can be combined in novel ways to create new machines.

"Think Legos," said Thomas Knight, a researcher at MIT's laboratory for artificial intelligence and the department of electrical engineering and computer science. Knight is a key player in efforts to build a library of "BioBricks" comprising the MIT Registry of Standard Biological Parts ( BioBricks are functional pathways — not just DNA segments — and typically code for operators, protein-coding regions, and transcriptional terminators. Some of the parts have been combined into logic gates.

Currently there are about 100 BioBricks, which are combined into "full circuits" in plasmids and expressed (usually in Escherichia coli) using traditional microbiology techniques.

Knight argued that synthetic biology requires an approach fundamentally different than traditional biology. His can-do attitude was evident in new studies designed "to engineer a simpler chassis and power supply" by stripping out redundant genes from the genome of bacterium Mesoplasma florum.

*First International Meeting on Synthetic Biology; MIT, June 10-12.
This work to create a "reduced" or minimal genome that provides room to insert desirable genes by deleting unnecessary ones builds on studies in 1999 conducted by J. Craig Venter and colleagues from The Institute for Genomic Research, which showed that no more than 350 protein-coding genes of the bacterium Mycoplasma genitalium are required to sustain life.

Fred Blattner, a pioneer in E. coli sequencing from the University of Wisconsin, good-naturedly jabbed at Knight. "This is fascinating, though, if I might say, a little overly enthusiastic," Blattner said. "We're going in the same line ... in attempting to get simplicity, but we're also trying to use an engineering principle of practicality."

Starting with the K12 strain of E. coli, Blattner has engineered several "multiple deletion strains" (MDS). His approach retains core genes required for growth on minimal media, while removing intervening sequences and "potential virulence genes, adherence genes, toxic genes, cryptic operons, and to do it all without leaving any remnants."

The current focus of Blatt-ner's work is strain MDS72, which will have roughly 20 percent less "stuff" in its genome. "3,700 genes is what nature is telling us you need to be a good E. coli," Blattner said, adding that since many of the deletions represent islands of pathogenicity, the stripped-down E. coli will also be safer to use.

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