In The Field

Synthetic Biology … What is That Again?

From a quiet Sunday morning, the synthetic biology meeting in Zürich Switzerland quickly exploded to roughly 300 in attendance. I had a chance to grab Tom Knight of MIT who demurred only slightly when asked about his involvement with synthetic biology. You might call him a founding father of the field. “I gave it a name at least,” he told me as we waited on a long lunch line amongst the other synth biologists grumbling that the cafeteria would only accept Swiss francs.

He was happy to give me some help in trying to define the field.

Coming from an electrical engineering background himself, he sees the approach to synthetic biology as fundamentally different from genetic engineering. The synthetic biologist is at heart an engineer, an inveterate tinkerer for whom understanding only comes with the act of building from the bottom up. He also said it was important to delineate synth bio from systems biology, to which it has often been compared. Systems biology has more of an emphasis on modelling, he says, which is important in synthetic biology, but not its end goal.

He offered a comparison of continuity that seemed helpful. I’m paraphrasing a bit, but the gist is this: Classic biology is a matter of discovery and collecting of facts to put them in an understandable framework. Systems biology looks to model that framework in a way that allows predictions to be made. Synthetic biology looks to create the system anew.

As if to immediately confuse that point, lunch was followed by a sprinter’s paced keynote address by George Church, also of MIT (actually, I believe Harvard Med is his primary affiliation, sorry), and one of the editors of Molecular Systems Biology (full disclosure Nature Publishing Group has a hand in this journal). Church has been placed at the forefront of both synthetic and systems biology, and he buzzed through maybe six projects going on in his lab that may speak to both, including engineering all of the amber (UAG) stop codons out of E. coli to “free up the genetic code,” and make those codons available for other amino acids generally unused by E. coli. His team has made, he says, 25 mutations changing G to A in a single strain, thanks in part to a novel recombination method that works at the replication fork. Wild stuff! He wasn’t sure if they’d need to hit all 326 known ambers, but mutating the release factor that responds to UAG during translation is still lethal in the strain with the 25 mutations. He’s not sure why yet. Church is also working on developing a mirror image of a polymerase to synthesize left handed DNA (no, not Z-DNA), and has been studying the co-evolution of bacterial strains engineered to rely on each other for specific metabolic processes.

The afternoon sessions also saw the first mention of minimal cells, a topic likely to cause a few ripples over the next couple of days. Giovanni Murtas of the University of Rome spoke about his group’s efforts to engineer liposomes with just the right mix of cellular components that they might become self sufficient and replicate. Having watched this field for some time, it’s clear that progress is slow. This bottom up approach is different from that at the J. Craig Venter Institute which has been trying to reduce the genome of a known organism Mycoplasma genitalium to its minimal needed parts. The group made waves recently when they attempted to patent the list of genes thought to be necessary for the bacterium to live, considering the novel organism a chassis for biofuel efforts. We’ll hear more about that tomorrow, when Hamilton Smith of the Venter Institute gives an 8:00am keynote.


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