Bacterial Cell with a Chemically Synthesized Genome

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  • #1
Gokul43201
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Scientists 'Boot Up' a Bacterial Cell With a Synthetic Genome

ScienceDaily (May 20, 2010) — Scientists have developed the first cell controlled by a synthetic genome. They now hope to use this method to probe the basic machinery of life and to engineer bacteria specially designed to solve environmental or energy problems.
...
"This is the first synthetic cell that's been made, and we call it synthetic because the cell is totally derived from a synthetic chromosome, made with four bottles of chemicals on a chemical synthesizer, starting with information in a computer," said Venter.

"This becomes a very powerful tool for trying to design what we want biology to do. We have a wide range of applications [in mind]," he said.

http://www.sciencedaily.com/releases/2010/05/100520131435.htm

Sounds really neat!

Reference: D. G. Gibson et al "Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome" Science, May 20, 2010 (DOI: 10.1126/science.1190719)

Link: http://www.sciencemag.org/cgi/content/abstract/science.1190719

Abstract:
We report the design, synthesis, and assembly of the 1.08-Mbp Mycoplasma mycoides JCVI-syn1.0 genome starting from digitized genome sequence information and its transplantation into a Mycoplasma capricolum recipient cell to create new Mycoplasma mycoides cells that are controlled only by the synthetic chromosome. The only DNA in the cells is the designed synthetic DNA sequence, including "watermark" sequences and other designed gene deletions and polymorphisms, and mutations acquired during the building process. The new cells have expected phenotypic properties and are capable of continuous self-replication.

See also: http://www.jcvi.org/cms/research/projects/first-self-replicating-synthetic-bacterial-cell/overview/
 

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  • #2
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Very exciting and neat indeed. It's not really surprising though, I knew it would come sooner or later.

For those that aren't quite sure how this is different from other genetic modifications basically it's the amount of genes modified. Genetic engineer 'changes' or manipulates a very small amount of genes relative to the amount of genes that are available in the organism. What they've done here is recoded basically the entire genome (actually I think it was the entire genome) of the organism such that it can self-replicate. This required something like 1 million basepairs... Quite a feat if you ask me :tongue:. I hope that this field continues to grow as it has been the last decade or so.
 
  • #4
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OMG OMG OMG OMG OMG OMG OMG *takes a deep breath*

OMG OMG OMG OMG OMG!!!! *wipes away a tear*

This is truly amazing. I've been waiting to see this in the news for years now.
 
  • #5
rhody
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Craig Venter has been doing gene sequencing a long time.

This http://www.ted.com/talks/craig_venter_on_dna_and_the_sea.html" [Broken] is a precursor of the announcement today.

This was filmed July 2005 I believe and in a little less than five years since it was made his researchers achieved their goal which started back in 1993.

Topics covered in the video, you can click on them just below the main display if you wish:

DNA and the Sea
Air Genome Project
Environmental Genomes
Engineered Species

The second http://www.ted.com/talks/craig_venter_is_on_the_verge_of_creating_synthetic_life.html" [Broken]

This video was filmed in Feb 2008, and posted a month later in March.
FYI, an interesting side note, they put watermarks in the code, which basically means they can write poetry in the DNA base pairs if they wish.

http://www.jcvi.org/"

http://www.edge.org/3rd_culture/bios/venter.html" [Broken]

excerpt:
DR. J. CRAIG VENTER is regarded as one of the leading scientists of the 21st century for his invaluable contributions in genomic research, most notably for the first sequencing and analysis of the human genome published in 2001 and the most recent and most complete sequencing of his diploid human genome in 2007.

He is Co-Founder, Chairman, CEO, Co-Chief Scientific Officer of Synthetic Genomics, Inc; as well as Founder, President and Chairman of the J. Craig Venter Institute. He was also the founder of Human Genome Sciences, Diversa Corporation and Celera Genomics. He and his teams have sequenced more than 300 organisms including human, fruit fly, mouse, rat, and dog as well as numerous microorganisms and plants.

Dr. Venter is also the key leader in the field of synthetic genomics. This work, trying to create the first synthetic genome, is leading to extraordinary advances in engineering microorganisms for many vital energy and environmental applications used at SGI. He is the author of more than 200 research articles and is among the most cited scientists in the world. He is the recipient of numerous honorary degrees and scientific awards including the 2008 National Medal of Science. He is also a member of many prestigious scientific organizations including the National Academy of Sciences.

He is the author of A Life Decoded: My Genome: My Life.

Rhody...
 
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  • #7
Ygggdrasil
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This is research that I've been following for quite a while. It's interesting to take a historical perspective and look over the advancements that led to this achievement. Like most science, this research came along painfully slowly, and the researchers ran into many obstacles and dead ends.

The research has its beginning in a simple question, "what is the minimum genome that an organism needs to survive?" The research began in 1995 when Venter and colleagues sequenced the genome of Mycoplasma genitalium, whose 580,070 base pair genome is the smallest of any free-living organism. These scientists then began to tinker with the M. genitalium genome, inactivating different genes, and four years later in 1999 published a paper showing that only about 250-350 of the bacterium's genes were essential for survival. However, they obtained this result by inactivating genes one-by-one and seeing if the bugs still lived. One could argue that there might be synergistic effects between genes, so even if gene A and gene B are individually not required for survival, knocking both out at the same time could kill the organism. It seemed the only way to really rigorously determine the minimal genome required for an organism was to synthesize a minimum genome from scratch and see if it could survive.

In 2003, Venter founded an institute to tackle this enormous challenge and raised millions of dollars to do so. He brashly proclaimed that within 3 years, his institute could chemically synthesize a bacterial genome from scratch. In reality, it took five years and in 2008, Venter's institute published that they had synthesized the first synthetic bacterial genome, the 580,070 base pairs of M. genitalium. However, in the meantime, the institute had also developed a method for transplanting the genome of one bacterium into another bacterium, research that they published in 2007. Thus, in 2008, Venter's institute seemed to have all the pieces in place to create a bacterium with a synthetic genome.

Of course, in science, nothing is ever straightforward. Although the small size of M. genitalium was advantageous, the bacteria grew really slowly greatly hindering the speed of the research. Biting the bullet, they decided to switch to using the genome of the related bacterium M. mycoides, whose genome was nearly twice as large as that of M. genitalium, but the bacteria grew much faster. After they had finally synthesized and assembled the M. mycoides genome, they transplanted the genome into the host and... nothing happened. It turns out that they had made an error in a single base pair in a very important gene, a typo that took about 3 months to discover and correct.

Of course, all of these publications that I've mentioned have been landmark discoveries. Figuring out how to efficiently synthesize and assemble a synthetic bacterial genome was a landmark discovery. Showing that it was possible to transplant a bacterial genome into a host cell of a different species was a landmark discovery. Yet, these were two small steps toward this study, also a landmark paper in the field of synthetic biology. However, from a broader view, this paper is also just a small step toward synthetic life.

While the bacterium that Venter and colleagues created contains a synthetic genome, it was placed into an already functioning host. Furthermore, the host bacterium is closely related to the M. mycoides genome the authors used, so many of the hosts' biological processes were compatible with the synthetic genome, allowing the host's machinery to correctly read the synthetic genome. Eventually the host's machinery gets entirely replaced with components from the synthetic genome. However, it is still unclear whether this approach can work with genomes containing significant portions of DNA that are unrelated to the host genome and require different regulatory machinery to work. This point will be crucial if these synthetic bacteria are to be created for biotechnological applications. Therefore, the next big step in this field will be to show that any arbitrary genome can be "booted" into any arbitrary host. And, based on what Venter's institute has shown before, I have a feeling that they might actually get this to work too.

References:
Fraser et al. 1995. The Minimal Gene Complement of Mycoplasma genitalium. Science 270: 397-404. doi:10.1126/science.270.5235.397

Hutchison et al.. 1999. Global Transposon Mutagenesis and a Minimal Mycoplasma Genome. Science 286: 2165 - 2169. doi:10.1126/science.286.5447.2165

Gibson et al. 2008. Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome. Science 319: 1215 - 1220. doi:10.1126/science.1151721

Lartigue et al. 2007. Genome Transplantation in Bacteria: Changing One Species to Another. Science 317: 632 - 638. doi:10.1126/science.1144622
 
  • #8
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Ygggdrasil, I commend you for your excellently researched and eloquently written post. Thanks a lot!
 
  • #9
rhody
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References:
Fraser et al. 1995. The Minimal Gene Complement of Mycoplasma genitalium. Science 270: 397-404. doi:10.1126/science.270.5235.397

Hutchison et al.. 1999. Global Transposon Mutagenesis and a Minimal Mycoplasma Genome. Science 286: 2165 - 2169. doi:10.1126/science.286.5447.2165

Gibson et al. 2008. Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome. Science 319: 1215 - 1220. doi:10.1126/science.1151721

Lartigue et al. 2007. Genome Transplantation in Bacteria: Changing One Species to Another. Science 317: 632 - 638. doi:10.1126/science.1144622

Nice job, Ygggdrasil

If you want full access to the articles and some partial content, you must subscribe http://www.sciencemag.org/subscriptions/indiv_register.dtl" [Broken] access is free though.

The site is great, almost every area in science is covered with well written current science articles. I found one on something I have wanted to post on for some time.

Rhody...
 
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  • #11
Andy Resnick
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I heard about the report this morning- it's an amazing step forward.

But mycoplasma don't have mitochondria or ribosomes, do they? They don't have a cell wall... Are mycoplasma closer to a virus than a bacterium?

http://en.wikipedia.org/wiki/Mycoplasma
 
  • #12
Ygggdrasil
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I heard about the report this morning- it's an amazing step forward.

But mycoplasma don't have mitochondria or ribosomes, do they? They don't have a cell wall... Are mycoplasma closer to a virus than a bacterium?

http://en.wikipedia.org/wiki/Mycoplasma

Because bacteria are prokaryotes, all bacteria, including mycoplasma, lack mitochondria (in fact, mitochondria are thought to derive from prokaryotes that were taken up by early eukaryotic cells). But, mycoplasma certainly contain ribosomes and their genes are closely related to those of other bacterial species. Perhaps the lack of a cell wall is one reason why Mycoplasma tend to have such compact genomes. Despite being relatively simple bacteria, mycoplasma are orders of magnitude more complex than viruses.

As an aside, scientists have been able to chemically synthesize some viruses from cell-free systems, a topic we recently discussed here (https://www.physicsforums.com/showthread.php?t=401033).
 
  • #13
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I want to live forever. I hope geneticists can grant me this wish one day.
 
  • #14
rhody
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I want to live forever. I hope geneticists can grant me this wish one day.

Mu naught,

If you were this guy, http://www.fantastic-voyage.net/" [Broken], you just might be able to afford it. He longs for the same thing. He has had genetic screening and is keenly aware of what genetic markers he has that may lead to disease. He aggressively treats himself with preventative measures for those conditions now, in hopes of prolonging his life long enough to be able to enjoy the fruits of gene research allowing him to live for a period well past a normal human lifespan. He has the money and access to the best experts in the field, giving him a better chance of prolonging his life more than most.

Rhody...
 
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  • #15
EnumaElish
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So when can we expect the Luddites/Frankenfood-ites in the US
The geographic origin of the term "Luddite" is Britain, and there is at least as much (probably way more) anti-GM public sentiment in the rest of the world as in the US.
 
  • #16
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Because bacteria are prokaryotes, all bacteria, including mycoplasma, lack mitochondria (in fact, mitochondria are thought to derive from prokaryotes that were taken up by early eukaryotic cells). But, mycoplasma certainly contain ribosomes and their genes are closely related to those of other bacterial species. Perhaps the lack of a cell wall is one reason why Mycoplasma tend to have such compact genomes. Despite being relatively simple bacteria, mycoplasma are orders of magnitude more complex than viruses.

As an aside, scientists have been able to chemically synthesize some viruses from cell-free systems, a topic we recently discussed here (https://www.physicsforums.com/showthread.php?t=401033).

+1 agree with everything said. In fact I believe that M.genitalium(SP?) has the smallest genome of any organism that isn't parasitic. It's still more complex than a virus though, but virus's are highly specialized cells.

I think the most important thing about mycoplasma having such small genomes is that it is easier to study them so we can gain knowledge about larger concepts in biology.

Ygggdrasil, also thanks for that extra research up above. :tongue:. I never knew that there were so many other people on these forums that like biology so much... I thought it was mostly engineers and mathematicians. :rofl:
 
  • #17
rhody
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Ygggrasil,

Dr Venter's company is on the cutting edge of Genomic research, that fact is without question. How will the results his team was able to achieve to be independently verified, or has it already been done ?

Rhody..
 
  • #18
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I guess I am not as optimistic as Yggdrasil that Venter or anyone else will have such good luck with arbitrary genomic implants into arbitrary hosts, unless the genome's source and the host are quite closely biologically or phylogenetically related to begin with. Certainly one would not expect a prokaryotic genome to function in a eukarotic host or vice versa since the genetic regulatory machinery is so different, not to mention the cellular organization itself. I even doubt if a Mycoplasma-type genome implanted into a typical prokaryote like E. coli would work for the same general reasons. Eventually, such heterologous transplants might be made to work by engineering into the introduced genome all the necessary regulatory sequences required for expression by the particular type of host or recipient cell used, when these are already known. However, I still expect some really daunting problems even with homologous transplants as investigators try to move up the phylogenetic ladder to more complex cell types.
 
  • #19
Ygggdrasil
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Dr Venter's company is on the cutting edge of Genomic research, that fact is without question. How will the results his team was able to achieve to be independently verified, or has it already been done ?

Given the large amount of work involved and the great expense required to construct synthetic genomes, I don't really foresee many other groups using this technology, at least in the near future. However, as the price of gene synthesis goes down, other groups may attempt to use these techniques for other applications.

I guess I am not as optimistic as Yggdrasil that Venter or anyone else will have such good luck with arbitrary genomic implants into arbitrary hosts, unless the genome's source and the host are quite closely biologically or phylogenetically related to begin with. Certainly one would not expect a prokaryotic genome to function in a eukarotic host or vice versa since the genetic regulatory machinery is so different, not to mention the cellular organization itself. I even doubt if a Mycoplasma-type genome implanted into a typical prokaryote like E. coli would work for the same general reasons. Eventually, such heterologous transplants might be made to work by engineering into the introduced genome all the necessary regulatory sequences required for expression by the particular type of host or recipient cell used, when these are already known. However, I still expect some really daunting problems even with homologous transplants as investigators try to move up the phylogenetic ladder to more complex cell types.

You bring up some good points, and I agree with many. I also doubt that the mycoplasma genome would function if transplanted into E. coli. However, I think there might be ways to make this work. For example, from Shinya Yamanaka's work on induced pleuripotent stem cells, we know that injecting a set of 4 transcription factors is sufficient to reprogram any human cell into a stem cell. Maybe it's possible to find a small set of mycoplasma transcription factors that, when introduced into host with the genome, would reprogram the host to allow the mycoplasma genome to "boot up" correctly. Of course, this approach would not be so general because it would be dependent on the specific genome being used.
 
  • #20
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There's a bit more detail in Venter's own press release, on the front of the TED site.

The work I'm more interested in is figuring out how these smallish genomes produce "life", that is, what is the individual task performed by (and physical mechanism employed by) each molecule that the genome codes for? Can anyone point me to where this sort of "reverse engineering" is done?
 
  • #21
rhody
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Ran across this today in the news today, May 23 2010, from: http://www.guardian.co.uk/theobserver/2010/may/23/observer-profile-craig-venter" [Broken]

Quite lengthy article that chronicles Venter's life: begins in 1968, in Vietnam during TET Offensive, interesting that he did not pursue his patent efforts after success in the Human Genome Project, but deferred to the requests of President Clinton, if he hadn't he would be one of the world's richest men by now:

excerpt:
He caused further outrage when he said he would not only beat that establishment club to the solution but patent the results. He eventually – arguably – made good the first part of that boast but, under pressure from President Clinton, gave up on the latter and agreed a joint declaration of the triumph with the official team in the millennium year, losing a fortune in the process. (Asked how he felt to have deciphered human life, Venter, who had designs on being "the first billionaire biochemist", replied: "Poorer.")
Since I am a physics admirer, I thought this observation by Freeman Dyson was interesting:
Freeman Dyson, the physicist, captured the full range of academic sentiment in this dry appraisal: "This experiment is clumsy, tedious, unoriginal. From the point of view of aesthetic and intellectual elegance, it is a bad experiment. But it is nevertheless a big discovery… the ability to design and create new forms of life marks a turning point in the history of our species and our planet."

and what others have said:
It's very easy to mock Venter," Jones suggests. "When he first appeared, people just kind of sneered at him. But they stopped sneering when they saw his brilliance in realising that the genome was not a problem of chemistry but a problem of computer power.

The last sentence above is particularly telling, a personal opinion that I share with Venter, not out of ego or wanting to be recognized, Ray Kurzweil and other noted leaders have stated for sometime that technologies ability to assemble large amounts of data is growing at an exponential rate, the Genome project, the four main experiments at the LHC and now research into this new area of Genomics cry out for a radical improvement in computing power, on the order of super exponential growth, tens of thousands of times faster then we have now, farms of distributed supercomputers sharing the load are simply inadequate to process what we have now. Not to mention the human coordination and communication required to create and maintain software required to do so. That is another technical and logistic nightmare in and of itself, not to mention actually processing the data from experiments.

As proof simply look how long it took the scientists an BNL to analyze and verify the collision data to finally announce discovery of Quark Gluon Plasma. I believe over two plus years. Not that the scientists were not being extremely careful in doing so, which may have accounted for some of the time. In any event, technological breakthroughs in this area are in demand, in the past some have risen to the challenge, and I have no doubt that it will happen again.

Rhody...
 
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  • #22
The last sentence above is particularly telling, a personal opinion that I share with Venter, not out of ego or wanting to be recognized, Ray Kurzweil and other noted leaders have stated for sometime that technologies ability to assemble large amounts of data is growing at an exponential rate, the Genome project, the four main experiments at the LHC and now research into this new area of Genomics cry out for a radical improvement in computing power, on the order of super exponential growth, tens of thousands of times faster then we have now, farms of distributed supercomputers sharing the load are simply inadequate to process what we have now.

Rhody, I completely agree with this assessment. When I first saw the headline, before even reading further or knowing about the process, my first thought was "computers can do that now?" I was also reminded of a statement Michio Kaku made on one of the more silly Science for Laymen TV shows on the Science Channel. I will paraphrase (I forgot the exact words):"The completion of the Human Genome project marks the start of a new era not of discovery but of mastery." In other words, using the information of genomes, which we already have, and building with them marks a new era in science. Much like the difference between the discovery of fire and finding creative ways of using it etc.
 
  • #23
rhody
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Rhody, I completely agree with this assessment. When I first saw the headline, before even reading further or knowing about the process, my first thought was "computers can do that now?" I was also reminded of a statement Michio Kaku made on one of the more silly Science for Laymen TV shows on the Science Channel. I will paraphrase (I forgot the exact words):"The completion of the Human Genome project marks the start of a new era not of discovery but of mastery." In other words, using the information of genomes, which we already have, and building with them marks a new era in science. Much like the difference between the discovery of fire and finding creative ways of using it etc.

Thomas,

Thanks, this has been gnawing at my soul now for the past two or three years, tapping some of the greatest minds out there through the wonder of Google/uTube/articles/professional papers has driven this point home again and again. I was planning to start a "discovery thread on emerging technologies in increasing computing power", I invite you to beat me to it. I am juggling two or three things right now personally/professionally and don't have time to do it the justice it deserves. I promise to contribute though, every time I find an interesting link, I squirrel it away for future use, I have a few ready to go.

Rhody...
 
  • #24
Thomas,

Thanks, this has been gnawing at my soul now for the past two or three years, tapping some of the greatest minds out there through the wonder of Google/uTube/articles/professional papers has driven this point home again and again. I was planning to start a "discovery thread on emerging technologies in increasing computing power", I invite you to beat me to it. I am juggling two or three things right now personally/professionally and don't have time to do it the justice it deserves. I promise to contribute though, every time I find an interesting link, I squirrel it away for future use, I have a few ready to go.

Rhody...
Perhaps this is offtopic: Warning:

Go for it. I am probably too biased, too entirely pro-science and technology, to post a lot about these topics. I have been looking all over the internet for people's opinions relating to advances such as this one and I only see two camps of popular opinion. One camp is very luddite or religious/spiritual and the comments from it say that Scientists are always up to bad things and the same people love to make distinctions between what they regard as the "natural" order and what to them is "unatural." Not only do I disagree but I am not quick to make those distinctions anyhow.

I simply don't subscribe to the paranoia of "what are Scientists up to now?!?"
I also don't think that anything artificial must be bad and that anything natural must be good. The world is not that simple to me.

The other camp of popular opinion is more on the fence "Science is capable of great things, but in the wrong hands ... so we should be cautious" It is probably the most rational but I still don't agree. I would say this is a more nuetral stance.

So where are the pro-technology people? Where are the people cheering who say "Let's throw caution to the wind"? This may be an incorrect stance but that does not mean it should not be represented. From my position the balance of opinion about technology looks terribly skewed towards ludditism. I seem to be the only proponent (even if in an armchair fashion.)

I mentioned this article to several people I know and not one of them was excited or even thought it was a good thing.

Are there other people like myself who only see the good in advancement? Sometimes I feel like the only person with this viewpoint.
 
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  • #25
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does anyone know if there is an expository paper somewhere that covers gibson et al 2008?
 

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