Archive by category | Synthetic

[Research highlight] Multicellular computers

Elaborate computation tasks can be performed by distributing the work across interconnected elementary information processing units. This principle underlies not only the operation of integrated electronic circuits, but also of many biological processes including development and, of course, the activity of the brain.  Read more

[Research highlight] Mycoplasma rebooted

Upshot of a series of four papers published over the last years (Gibson et al, 2010, Lartigue et al, 2009, Gibson et al, 2008, Lartigue et al, 2007), J. Craig Venter’s team now reports the successful transplantation of a chemically synthesized genome into a host bacterial cell (Gibson et al, 2010). As proof of principle, a slightly altered Mycoplasma mycoides genome (JCVI-syn1.0) was synthesized, assembled and transplanted into M. capricolum recipient cells.  Read more

Rewiring E. coli transcriptional network

Rewiring E. coli transcriptional network

Gene duplications and mutations are central driving forces in the evolution of genomes. Genomes must be robust to such changes in order to be evolvable, and many studies have probed genome robustness using systematic gene knockouts or overexpression experiments. In a recent paper, Isalan et al. (2008) took a new approach to test the robustness of Escherichia coli gene circuitry by reconstructing gene duplication events by shuffling the promoter-ORF pairs for about 300 transcription factors and introducing 598 recombined pairs one-by-one into E. coli to rewire its transcriptional network. Surprisingly, ~95% of such additions are robustly tolerated, and some networks even exhibit greater fitness under various selection pressures. Moreover, the study shows that, in contrast to naive expectations, the introduction of positive or negative feedback loops has little effect on the protein expression levels of regulated ORFs.  Read more

Contrasts: Craig Venter and NSABB on synthetic biology

Contrasts: Craig Venter and NSABB on synthetic biology

Two rather contrasting videos on synthetic biology this month. In the first videocast, released by TED, Craig Venter exposes his grand vision of synthetic genomics. He insists on the notion of ‘combinatorial genomics’, that will combine the power of large scale DNA synthesis (‘robots that can make a million chromosomes a day’) with a database of 20 million genes, ‘the design components of the future’. This approach, a pragmatic mixture of rational function-oriented design and empirical large-scale selection, is envisioned to prepare a modern ‘Cambrian explosion’ of new synthetic species. It is good to see Craig Venter laughing when announcing casually the ‘modest goal of replacing the entire petro-chemical industry’.  Read more

JCVI-1.0

A few weeks ago, Jason Kelly explained in his post how Itaya and colleagues (2007) assembled the complete 135 kb rice chloroplast circular genome starting from a collection of 5-6 kb fragments and using sequential in vivo homologous recombination in Bacillus subtilis. Now, Hamilton Smith, Craig Venter and colleagues have achieved the assembly of a complete 583 kb Mycoplasma genitalium genome (“JCVI-1.0”, Gibson et al, 2008). The starting fragments were of similar length, 4-5 kb fragments with 80-360 kb overlaps, albeit synthesized chemically rather than by PCR. In contrast to Itaya et al, Ham Smith’s team used in vitro recombination (using T4 pol digestion/annealing/Taq pol repair and ligation) in a 3 step hierarchical assembly process and completed the fourth step, the assembly of 4 quarter genomes, using in vivo homologous recombination in yeast (TAR cloning, Larionov et al, 1996).  Read more

New method for writing genomes

Costs for de novo synthesis of DNA fragments (<10kb) are decreasing rapidly, and challenges now lie in the assembly of these fragments into ever-larger sequences. One of the main challenges is the fragility of long DNA sequences during the in vitro steps associated with traditional methods for assembling DNA. In a recent publication, Itaya et al (2007) describe a method for assembling 4-6kb DNA fragments in vivo via incorporation in the B. subtilis genome. They demonstrated this homologous recombination-based method by assembling the 134.5 kb rice chloroplast genome from 31 smaller fragments.  Read more

Visualizing the neuroanatomical code of memory

Visualizing the neuroanatomical code of memory

In a very elegant study published last week in Science, Mark Mayford and colleagues use a synthetic bistable genetic switch to visualize the activity of neurons during associative learning in mice (Reijmers et al, 2007). The reporter system (called TetTag) has two components (see drawing, adapted from Reijmers et al, 2007): 1) the tTA transactivator (tetR-VP16) is placed under the control of the immediate-early gene fos; 2) a tetO-regulated bidirectional promoter drives the expression of both a tau-LacZ reporter and a mutated tetracycline-insensitive version of the tet transactivator, *tTA (tTAH100Y).  Read more