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Artificial life, a step closer

Researchers at the J. Craig Venter Institute in Rockville, Md., say they've joined together chemically synthesized fragments of DNA to assemble the synthetic genome of the world's smallest free-living bacterium. Previously, only viral genomes had been synthesized in the lab, but synthesizing the genome of __Mycoplasma genitalium__, a bacterium that inhabits the genitals and respiratory tracts of primates, represents the first bacterial genome and the largest molecule of defined structure ever m

By | January 24, 2008

Researchers at the J. Craig Venter Institute in Rockville, Md., say they've joined together chemically synthesized fragments of DNA to assemble the synthetic genome of the world's smallest free-living bacterium. Previously, only viral genomes had been synthesized in the lab, but synthesizing the genome of __Mycoplasma genitalium__, a bacterium that inhabits the genitals and respiratory tracts of primates, represents the first bacterial genome and the largest molecule of defined structure ever made by humans. The project moved the linkurl:Venter group;http://www.the-scientist.com/article/display/18857/ a step closer to their ultimate goal of creating the world's first linkurl:synthetic organism,;http://www.the-scientist.com/article/display/18854/ which then might be used to manufacture biofuels and other compounds. Harvard geneticist linkurl:George Church,;http://www.the-scientist.com/article/display/15402/ who was not involved with the study, told __The Scientist__ that it was "an important milestone rather than a breakthrough." The findings, which appear today (Jan 24) in the online version of __Science__, follow a linkurl:paper;http://www.the-scientist.com/news/display/53341/ published by the Venter Institute's linkurl:synthetic biology;http://www.the-scientist.com/article/display/18855/ and bioenergy group in 2007 showing that it was possible to insert the genome of __Mycoplasma mycoides__ into the closely related __Mycoplasma capricolum__. (Here is the linkurl:abstract;http://www.sciencemag.org/cgi/content/abstract/1151721 of the new paper.) This time, the Venter team pieced together five to seven kilobase-long cassettes of chemically synthesized DNA in vitro to make four 144 kilobase strands of DNA. They then cloned these as bacterial artificial chromosomes in __E. coli__ and transferred the chunks of DNA to yeast cells. There, they were cloned and assembled into a complete 582 kilobase genome, which contains 485 protein-coding genes. J. Craig Venter, who sits on the scientific advisory board of __The Scientist__ and was an author on the paper, called the study "a very exciting advance" in a press briefing he and his coauthors held today. Venter said that the next step is to "boot up" the artificial genome by implanting it into a cell and getting that cell to express the synthetic genes. "There are multiple barriers to this," warned Venter. "It isn't just a slam-dunk, or we would be announcing it today." Other researchers share the Venter group's goal of creating biofuels by co-opting the genetic machinery of microorganisms. Church, who founded the biotech company linkurl:LS9,;http://www.ls9.com/ said that his company is approaching the challenge from a different angle. At LS9, researchers reprogram the genome of __E. coli__ to metabolically produce a petroleum-like product. Church said he believes LS9's approach may prove to be more efficient. "It might be that just starting with an organism that has lots of metabolic capabilities already might be a better biological platform," he said. Church suggested that reprogramming an existing genome may turn out to be less costly than completely synthesizing a new genome that requires the use of two other organisms. "LS9 is actually making biofuels with way fewer than 70 changes [to the genome of __E. coli__]," he said. Venter explained that another of his companies, linkurl:Synthetic Genomics,;http://www.syntheticgenomics.com/index.htm is already altering existing genomes to harvest useful chemicals, but that his current work will usher in a "new design phase of biology." "Starting with design in the future, I think, will be the method of choice," he said, "once we know in fact it is doable. I am 100 percent certain [this] will be the process of choice." UPDATE (Jan. 25, 9:37 a.m EST): Link to __Science__ abstract added.
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Avatar of: Andras Pellionisz

Andras Pellionisz

Posts: 11

January 26, 2008

The key appears to be, which is the better platform to understand genome regulation. The major landmark by Venter is the synthesis of (the smallest) full genome - with its 468 genes plus 7% intergenic (by 1995 admittedly operonic) regulatory mechanism. While my bet is that the full genome (synthetized or natural, since they can be made identical) will "boot" - it will tell a lot about genome regulation if the "stripped down" ("minimal genome") that is an about 25% reduced set of genes (with the regulation kept for the full deck) would, indeed, "boot". (Even if it "kicks in", it just might "limp along" - in the fragile and extremely slow-growing mycoplasma G. it is hard to tell). \n\nWithout the regulatory (intergenic) system tailored to the reduced set of genes the "minimal genome" might not boot at all - that might be Venter's concern that it "isn't a slam dunk". Technically, the entire intergenic mechanism is less than 50 kb (much smaller set of information than a very low quality digital image of a small stamp-size picture). The underlying principle of recursive genome function (publication by AJP in press, accepted by peer-review) should significantly help. \n\nIn the significantly larger e-coli, figuring out how to tailor the regulation to an altered (e.g. synthetic) genome is more complex, but there isn't just a single bunch of "low hanging fruits" ("designer genomes"; such as for biofuels).\n\nThere are two more extremely important practical goals:\n\n1) Understanding of the regulatory system will yield the means of "halting" runaway microbes (by driving their regulation into the ground) - a chief goal for those demanding safe progress of this emerging field (as well as in biodefense).\n\n2) Understanding the regulatory system will yield the "antibiotics of a new type" - that work by shutting down their system by throwing monkey wrenches into their regulation. This is highly important, e.g. against those microbes that operate in a "stealth" (resistive) mode, evading the immune system by re-appearing with their regulation re-configured. (Interestingly, for the Venter-camp the practical goal might be the opposite to "running regulation to the ground" - since the Mycoplasma G. already operates in a massively down-regulated fashion, to evade the immune system of the host. Thus, for instance for massive H2 production, all such brakes should rather be "released" to go "full steam". Again, in the minuscle 50 kb system identifying and knocking out the "breaks" of recursion should be simpler than "turning the keys on and off" in the much larger "organ"-ism that the fully configured e-coli appears to be).\n\nSee more background on these exciting issues at the junk DNA portal \n\npellionisz_at_junkdna.com
Avatar of: Celeste Matthews

Celeste Matthews

Posts: 4

December 15, 2009

Artificial life leaves the reader to believe that a new organism has been created out of mere chemicals. Because Louis Pasteur's theory of biogensis is hard to disprove, a truly artificially formed life would be significant in our understanding of evolutionary processes. This sounds very much like one more genetic engineering project along the line of glow in the dark rats or roundup ready soybeans.

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