Synthetic Life

Reply Tue 11 Sep, 2012 05:28 pm
A method was found in the Harvard Medical School which has allowed has devised a method for making hundreds of changes in a genome simultaneously.
Mice and humans have a 10% difference in our genome. So we start with synthesizing the entire mice's genome, and then plop it inside a solution filled with synthetically made phospholipids. So the phospholipids automatically forms micelle. Now with the synthetic mice's embroyo, and looking at the genome, we see where the mice's genome differ from our genome, then alter however many sites at which the mice's genome differ from that of the human simultaneously. Of course, the genome is altered at a large scale. So the mice's embroyo is "hijacked" and the new codons will lead to new programming instructions that will create a human. Voila, if it works, then we have become like a God, and created life.

This has been successful with bacteria. Bacteria's with 10% difference in their genome. One is an e. coli and another is a bacteria that infects goats.


Synthetic biology, the quest to hijack living systems and convert them to human-directed goals, is on the march. Last year biologists synthesized the entire genome of a small bacterium and showed how it could successfully infect a second bacterium. Now, in what may be a more significant advance, biologists have shown they can radically change a genome, not just copy it.

A team led by Farren J. Isaacs and George M. Church of the Harvard Medical School has devised a method for making hundreds of changes in a genome simultaneously. This massively parallel intervention, as the changes are known, is one of the advances that would be needed in another project Dr. Church and others have contemplated, that of recreating the mammoth by starting with an elephant’s genome and changing it at the 400,000 sites at which elephant DNA differs from that of the mammoth.

In the present instance, Dr. Isaacs and Dr. Church have been working not with a mammoth but with the standard laboratory bacterium known as E. coli. To prove they can seize control of the microbe’s genetic code and reprogram it, they have focused on one of the code’s 64 elements, known as the amber stop codon.

In Thursday’s issue of the journal Science, they report that they will soon be able to delete the amber stop codon from all 314 sites where it occurs in the E. coli genome, without harm to the organism. The codon can then be reinserted, but with a new function, like introducing a novel chemical unit into the bacterium’s proteins.

Genetic engineers have become adept at changing one gene in a genome, but it is quite another thing to alter a genome at 314 sites simultaneously.

“This is the first instance that a genome has been altered at such a large scale,” said James J. Collins, a synthetic biologist at Boston University. Along with the synthesis of a bacterial genome last year by J. Craig Venter, the advance takes synthetic biology from the gene to the genome level.

“It is a major technical breakthrough which has great promise for scientific breakthroughs to follow,” said Dr. Gerald J. Joyce, a biologist who studies the origin of life at the Scripps Research Institute in San Diego. “This is really macho molecular biotechnology.”

By taking control of the amber stop codon, Dr. Isaacs and Dr. Church have opened a door into the bacterium’s genetic programming. They could now make the bacterium incorporate a novel kind of amino acid unit into its proteins, although they have not yet done so, to Dr. Joyce’s disappointment.

“They could have taken their amber codon and put in something blinky there,” he said, like a dye that would have made the bacterium fluoresce.

The two leading laboratories that have taken synthetic biology to the genome level are those of Dr. Venter and Dr. Church, but their approaches are very different. Dr. Venter’s company, Synthetic Genomics, spent $500,000 to make a synthetic copy of the genome of a bacterium that infects goats. Dr. Church has focused on changing an existing genome — that of the well-studied E. coli bacterium — thus avoiding the high cost of sequencing.

Dr. Church said his approach was modular, so it could be tested at each stage, whereas Dr. Venter’s whole genome was nearly brought down by a single mutation. In contrast to Dr. Venter’s method, “our genome engineering technologies treat the chromosome as an editable and evolvable template,” Dr. Church says in his Science article.

Dr. Venter was not available for an interview, but his office issued a statement in which he said his goal — to design cells from scratch — could be attained only by whole-genome synthesis. He called Dr. Church’s approach, without excessive praise, “a positive addition to the field.”

Dr. Joyce of the Scripps Research Institute summed it up this way: “Craig builds the house from scratch, and George is more the remodeler, but they are both interesting houses to live in.”

The goal of synthetic biology is to take control of nature’s manufacturing system and divert it to other ends. Dr. Church’s method, which has been seven years in development, focuses on the genetic code that is common to all living things. The four different bases of DNA can be combined to make 64 three-letter words, or codons, the units in which the cell translates its genetic information into protein products.

What Dr. Church has done is to grab one of these codons for his own use by forcing the bacterium to stop using it. In future experiments he can assign this codon to other uses.

Most of the codons in the genetic code are used to designate one or another of the 20 standard amino acids that make up proteins. But three of the units are punctuation marks, all signaling to the cell to stop adding to a growing chain of amino acids. The chain is then released and folds up into a protein.

The E. coli bacterium uses all three stop codons, which are known as amber, ocher and umber (the first is named for Harris Bernstein, a former graduate student at the California Institute of Technology whose surname means amber in German). Dr. Church’s team converted all 314 amber stop codons in the E. coli genome to the ocher variety by changing all instances of T-A-G, in the four-letter alphabet of DNA units, to T-A-A.

The ocher stop codon works just as well as amber and, after one final step — yet to be completed — the team will have an E. coli bacterium that is not dependent on amber. They will then delete the gene whose protein recognizes the amber codon and forces a break in the protein chain. That will allow them to reinsert amber codons and, with a method devised by Peter G. Schultz of the Scripps Research Institute, reassign them to incorporate a novel amino acid into the bacterium’s proteins.

Charles R. Cantor, chief scientific officer of Sequenom, a genetic analysis and diagnostics company in San Diego, said the new method was “wonderful because it would allow expansion of the genetic code to a 21st amino acid genomewide.”

Other codons are available to be hijacked by Dr. Church’s method, and the bacterium in principle could be forced to operate an entire chemistry that was orthogonal to its own, as synthetic biologists say, meaning it had no interaction with the microbe’s natural chemistry.
A version of this article appeared in print on July 15, 2011, on page A14 of the New York edition with the headline: Genetic Code of E. Coli Is Hijacked by Biologists.
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Reply Tue 11 Sep, 2012 05:35 pm
@Atom Blitzer,
Makes you think of "crowd sourcing" in a new light.

Or....Some people are full of s*** and some s*** is full of people.
Atom Blitzer
Reply Tue 11 Sep, 2012 09:43 pm
Do you believe it will be possible to synthesize life from just inanimate chemicals in your life time?
Reply Wed 12 Sep, 2012 07:38 am
@Atom Blitzer,
Difficult to predict the when. Think it will be achieved. Then I wonder about sentience and abilities of such an alien form.
Atom Blitzer
Reply Wed 12 Sep, 2012 11:30 am
Interesting that you mentioned aliens. Most people think of space when they think alien life forms. But I think there is more chance of encountering life forms in a test tube right here on earth. There is the immortal molecule which is a RNA molecule made by a biologist that keeps on mutating and passing it's codons to progeny. Since it doesn't have DNA, biologists argue if it's alive.


A few years after Tracey Lincoln arrived at Scripps Research from Jamaica to pursue her Ph.D., she began exploring the RNA-only replication concept along with her advisor, Professor Gerald Joyce, who is also dean of the faculty at Scripps Research. Their work began with a method of forced adaptation known as in vitro evolution. The goal was to take one of the RNA enzymes already developed in the lab that could perform the basic chemistry of replication, and improve it to the point that it could drive efficient, perpetual self-replication.

Lincoln synthesized in the laboratory a large population of variants of the RNA enzyme that would be challenged to do the job, and carried out a test-tube evolution procedure to obtain those variants that were most adept at joining together pieces of RNA.

Ultimately, this process enabled the team to isolate an evolved version of the original enzyme that is a very efficient replicator, something that many research groups, including Joyce's, had struggled for years to obtain. The improved enzyme fulfilled the primary goal of being able to undergo perpetual replication. "It kind of blew me away," says Lincoln.

Immortalizing Molecular Information

The replicating system actually involves two enzymes, each composed of two subunits and each functioning as a catalyst that assembles the other. The replication process is cyclic, in that the first enzyme binds the two subunits that comprise the second enzyme and joins them to make a new copy of the second enzyme; while the second enzyme similarly binds and joins the two subunits that comprise the first enzyme. In this way the two enzymes assemble each other — what is termed cross-replication. To make the process proceed indefinitely requires only a small starting amount of the two enzymes and a steady supply of the subunits.

"This is the only case outside biology where molecular information has been immortalized," says Joyce.

Not content to stop there, the researchers generated a variety of enzyme pairs with similar capabilities. They mixed 12 different cross-replicating pairs, together with all of their constituent subunits, and allowed them to compete in a molecular test of survival of the fittest. Most of the time the replicating enzymes would breed true, but on occasion an enzyme would make a mistake by binding one of the subunits from one of the other replicating enzymes. When such "mutations" occurred, the resulting recombinant enzymes also were capable of sustained replication, with the most fit replicators growing in number to dominate the mixture. "To me that's actually the biggest result," says Joyce.

The research shows that the system can sustain molecular information, a form of heritability, and give rise to variations of itself in a way akin to Darwinian evolution. So, says Lincoln, "What we have is non-living, but we've been able to show that it has some life-like properties, and that was extremely interesting."

Knocking on the Door of Life

The group is pursuing potential applications of their discovery in the field of molecular diagnostics, but that work is tied to a research paper currently in review, so the researchers can't yet discuss it.

But the main value of the work, according to Joyce, is at the basic research level. "What we've found could be relevant to how life begins, at that key moment when Darwinian evolution starts." He is quick to point out that, while the self-replicating RNA enzyme systems share certain characteristics of life, they are not themselves a form of life.

The historical origin of life can never be recreated precisely, so without a reliable time machine, one must instead address the related question of whether life could ever be created in a laboratory. This could, of course, shed light on what the beginning of life might have looked like, at least in outline. "We're not trying to play back the tape," says Lincoln of their work, "but it might tell us how you go about starting the process of understanding the emergence of life in the lab."

Joyce says that only when a system is developed in the lab that has the capability of evolving novel functions on its own can it be properly called life. "We're knocking on that door," he says, "But of course we haven't achieved that."

The subunits in the enzymes the team constructed each contain many nucleotides, so they are relatively complex and not something that would have been found floating in the primordial ooze. But, while the building blocks likely would have been simpler, the work does finally show that a simpler form of RNA-based life is at least possible, which should drive further research to explore the RNA World theory of life's origins.

The paper is titled "Self-sustained Replication of an RNA Enzyme," and the work was supported by NASA and the National Institutes of Health, and the Skaggs Institute for Chemical Biology..

Abstract : http://www.sciencemag.org/content/323/5918/1229.abstract
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Reply Sun 25 Jan, 2015 11:49 am
More advances in artificial genomes...
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