The Seven Stones

SB3.0 day 1

Today was the first day of the Synthetic Biology 3.0 conference, held this year in Zurich and organized by Sven Panke, Matthias Heinemann, Jörg Stelling and Martin Fussenegger. For those who would like to have a definition of what Synthetic Biology is, there are very instructive explanations here by Drew Endy.

Here are some subjective snapshots of some of the talks that were presented today.

The inaugural keynote lecture, “Reading, Writing and Evolving Genomes” was given by George Church (https://arep.med.harvard.edu, also Senior Editor of Molecular Systems Biology). Even if he did not make it too easy for the poor blogger to summarize this speedy talk :-), George provided a very impressive overview of the fascinating opportunities offered by advances in synthesis, automated recombination, evolution and next-generation sequencing technologies. Not satisfied with creating new life, the lab is now planning to synthesize a mirror form of life! As a starter, the complete in vitro synthesis of a (chirally) mirror version of Sulfolobus DNA polymerase IV has been undertaken. On the theme of massive DNA engineering, he presented the application of a highly efficient single-stranded DNA recombination method (see Costantino and Court, 2003) to oligonucleotide pools. Using automated cycles of electroporation with pools of oligos, this method will ultimately allow whole genome redesign in E. coli, for example to mutate all amber codons into UAA, thus “freeing” the UAG codon for orthogonal systems based on a redefined genetic code. Finally, after evolving an artificial symbiotic association between a strain deficient in tyrosine biosynthesis and another deficient in tryptophane biosynthesis, polony sequencing reveals that only a very few classes of mutations are selected (some data are presented in Shendure et al 2005), a result very similar to what Palsson and colleagues have observed (Herring et al, 2006).

The topic of evolution appeared also in the talk presented by Luis Serrano (yes, Luis is also on our board…), who introduced new links into the transcriptional network of E. coli by expressing rearranged promoter/transcription factor cassettes. From hundreds of strains screened, it appears that additional links in the network do not cause major growth phenotypes. However, some of the strains behave like “superstrains” that can overgrow the wildtype strain and thus can be selected under selective pressure, illustrating the potential for evolvability of the network by addition of new links.

Nice presentations were given by two young teams of last years iGEM competition (Imperial and Ljubljana), illustrating the more applied side of synthetic biology, which makes full use of standardized reusable parts to quickly go through the typical engineering cycle of specification, design, modeling, implementation and testing.

Finally, Georg Seelig presented his recent work on DNA-based logical gates (Seelig et al 2006) that work exclusively on the basis of base-pairing and strand-displacement reactions, showing that synthetic biology can even extend to purely in vitro and cell-free systems (Simpson 2006).

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