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‘Minimal’ cell raises stakes in race to harness synthetic life
- nsxwolf 11y agoMinimal cell, or minimal genome? I don't think we're anywhere near capable of creating a synthetic cell, minimal or not.
- tosseraccount 11y agoMinimal genome ... which also means the minimal viable cell. They are trying to figure out what is the minimal amount of genes to create a cell that can survive and reproduce. Craig Venter, the researcher from the Nature article, claimed to have built "artificial life" earlier in 2010. The new Nature article is reporting he's claiming to have made a "new species". An article on Venter's group's 2010 work: https://www.theguardian.com/science/2010/may/20/craig-venter-synthetic-life-form https://www.theguardian.com/science/2010/may/20/craig-venter... ... "Craig Venter and his team have built the genome of a bacterium from scratch and incorporated it into a cell to make what they call the world's first synthetic life form" The recent 2016 Science journal article is here : http://science.sciencemag.org/content/351/6280/aad6253 http://science.sciencemag.org/content/351/6280/aad6253 "JCVI-syn3.0 is a working approximation of a minimal cellular genome, a compromise between small genome size and a workable growth rate for an experimental organism. It retains almost all the genes that are involved in the synthesis and processing of macromolecules. Unexpectedly, it also contains 149 genes with unknown biological functions, suggesting the presence of undiscovered functions that are essential for life. JCVI-syn3.0 is a versatile platform for investigating the core functions of life and for exploring whole-genome design." One question I would have is "Are there homologs to the 149 unknown function genes in the human genome"?
- stcredzero 11y agoThere are probably some things we don't know about the insides of a bacterium, and there are probably some fabrication techniques to be worked out, but I would expect the knowledge of how to fabricate a whole cell from scratch within a decade. (I know little of molecular biology, so this is a wild layman's guess.)
- kyberias 11y agoThe original article uses these concepts interchangeably: minimal genome and minimal cell. They basically define the minimal cell as a cell with a minimal genome. E.g. "Because our minimal cell is largely lacking in biosynthesis of amino acids, lipids, nucleotides, and vitamins, it depends on the rich medium to supply almost all of these required small molecules."
- tosseraccount 11y agoHumans need a lot of them, too ... but , yeah, a special bacteria chow for these critters is a good idea.
- dekhn 11y agoI don't think it necessarily follows that a minimal genome has the minimal cell or vice versa. It really depends on how much support structure (the rich media) is provided and the specific details of how the genome produces the cell structure, and the cell structure details. One can imagine little cycles of genes that all need each other, but don't actually provide any extra fitness. IIRC the Venter method can't identify and remove those sorts of cyclic dependencies if the cycle is more than 1-2 long.
- kyberias 11y agoOh and to answer your question, there are at least some homologs: https://d2ufo47lrtsv5s.cloudfront.net/content/sci/351/6280/aad6253/F6.large.jpg?width=800&height=600&carousel=1 https://d2ufo47lrtsv5s.cloudfront.net/content/sci/351/6280/a...
- logfromblammo 11y agoThat isn't exactly "from scratch". They took pre-existing genes from a known bacterial genome (M. mycoides) and started knocking out genes via an automated process until the final resulting genome was no longer viable if any of the remaining genes were likewise removed. That doesn't quite meet my definition of synthetic life form. It's like the difference between stripping down a stock car for racing and building an entire go-kart from unrefined, unsorted piles of rock. That synthetic genome is the end product of billions of years of evolution minus billions of years of accumulated kludges and cruft. And it's about half a megabyte. It wasn't designed, but discovered. I would guess that there are plenty of genes in the sequences common to fungi, plants, and animals that cannot be removed without ruining the whole organism. Many of those would have currently unknown functions. And those 149 genes are what remain from running the cruft-removal process on one species of bacterium. To determine whether they are truly required for life, they woul have to also be retained after running the process on other species to discover their minimally viable genomes.
- SapphireSun 11y agoI think you guys are missing the point a bit. The important thing here is that there's a minimal genome in a working organism that can be used as a research platform. The "from scratchness" level is purely for bragging as once the cell divides a few times and fails to maintain components, it'll be working from the set of things its genome specifies. Whether you consider that cheating isn't really relevant for the potential experiments you can run. EDIT: For a CS example, imagine trying to reverse engineer a computer system and make it do things it wasn't supposed to do. It's a lot easier to tinker with hardware from an Apple ][ than with a modern x86 chip. The advance here is that we are finding the Apple ][ in the x86 chip and doing a run of those for people who want to play with them.
- jonnathanson 11y agoExactly. Furthermore, you don't need to build life from scratch. That's wasteful. You'll just set yourself back years, possibly a decade or more, trying and erring until you get to roughly the same place as the stripped-down bacterial genome at which Venter and his colleagues have arrived. Venter isn't explicitly trying to create life from scratch; he's trying to find the minimum viable platform from which to harness life for various useful purposes. Starting from the proverbial "pile of unrefined rock" would accomplish nothing but scoring a few vanity points.
- hirenj 11y agoI went to the article to try and dig up information about the orthologues, but as is kind of par for the course these days, the meat of the useful information is not readily available. If you go to the supplementary information, you can find an excel sheet with the locus and amino acid sequences for all the genes. It's then just a matter of blasting the unknown function genes against the human genome and using a cutoff for similarity. I'm going to have to wait to do this next week, but if any enterprising soul wants to do this, you can get the supplementary data here: http://science.sciencemag.org/content/351/6280/aad6253/suppl/DC1 http://science.sciencemag.org/content/351/6280/aad6253/suppl...
- sevenless 11y agoLooking at that supplementary Excel spreadsheet, only 42 of those essential genes are annotated as "hypothetical protein/unknown function/unclear functional category". For example, locus MMSYN1_0421 has unknown function, but belongs to the alkaline shock protein family, so we can't say we have no idea what it does. They seem to be the only loci where we're truly in the dark. There are many more with "putative" or "probable" roles and known homologs. In total the headline seems to be misleading. We're only truly lost on about 9% of these essential genes.
- kyberias 11y agoWhat exactly are your criteria for a "synthetic cell"?
- nsxwolf 11y agoThe cell itself being synthetic, not just the genome. Not a cell from nature that's had its genome removed.
- kyberias 11y agoYou should realize that it's effectively the same thing. The bacterial genome synthesizes everything in the cell.
- nsxwolf 11y agoIs that true? You can take a naked genome, and do something to it, and a cell will materialize? With a cell wall and cytoplasm all its mitochondria and everything?
- tantalor 11y agoYeah the "do something" black box includes a cell replication step. Given genome, 1. Replace genome in host cell 2. Replicate host cell 3. Output "materialized" cell
- kyberias 11y agoWell, they had to have a receptive cell to bootstrap this thing, that is true. Yet, since we're talking about mycoplasma here, they don't have a cell wall (only plasma membrane) nor mitochondria (only eukaryotes have those). The new minimal genome really has to synthesize everything needed by the cell to grow and divide.
- tdaltonc 11y agoThey're not. If you put a synthetic genome in to a cell that's just had the genome removed, that's very different then starting with pure molecules and building something that will boot.
- crispyambulance 11y agoCreating an actual cell from scratch would be very difficult but not particularly compelling. The synthetic genome gets "transplanted" into a host cell (in this case the M.capricolum baterium), from that point on, it "IS" the new organism and divides as such. And anyway, there's a tremendous amount of stuff to study with "the platform" of a transplanted genome. Venter should probably get the Nobel prize twice-- once for shotgun sequencing and at least once (if not twice) for synthetic biology. These are huge advancements.
- dekhn 11y agoI would say it's the new organism only after nearly all the old host cell components have decayed away. In the meantime, it's a hybrid. Then the new genome starts transcribing and translating new proteins to replace the host cell's components, and due to aging/entropy/repair eventually all the old components will be gone. Venter didn't invent shotgun but he did popularize it. He was a top-notch biologist even before he switched to genomics, though, and that work was good enough that I think had he kept to it, he may very well have won the prize eventually. Likely, Venter will not win the prize for several reasons. He's political- too many people hate him. Most of his work is viewed as "technical" by the scientific community. The words "obvious" and "boring" seem to be the things that I hear most levied against his efforts.
- dghughes 11y agoI wonder would it be possible to accelerate a synthetic cell's evolution via software? If you already know exactly what's in the cell (you built it!) could a computer speed up its life via a software model and jump ahead to something more complex which you build as version 2?
- daveguy 11y agoThat would be awesome, but it is unlikely with current software and hardware. Even small scale simulations (nanoseconds to microseconds of a single protein molecule) require hours of sim time (on large clusters).
- saalweachter 11y agoTo elaborate, time is the problem. The number of atoms in the smallest viable cell is actually reasonably small, less than a billion atoms, such that you could hope to store it all in memory on a single beefy computer. Meanwhile, you need something like picosecond resolution in the simulation, while you need seconds of simulated time to see interesting macro-level things happen. If you want to see cell division, you're probably talking a minimum of thirty minutes of simulated time.
- ealloc 11y agoNot to mention that the molecular dynamics simulations you're describing can't actually simulate chemical reactions. (the covalent bonds can't change in the sim, unless you do a much more intensive QM calculation and even that's iffy).
- gpvos 11y agoIf you want evolution, you would also have to simulate the cell's environment. Without an environment, there's no natural selection and thus no evolution.
- adrianN 11y agoIt would be cool to play with this idea using the OpenWorm platform.
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- justsaysmthng 11y ago> Church says that genome-editing techniques will remain the go-to choice for most applications ... George Church is kind of a sarcastic name for a genetic scientist.. But the ethics question is more open then ever. Didn't you immediately think about how cool it would be if we could program these organisms to do stuff ? I did. Could you then program it to become multi-cellular ? How long before this can be achieved ? 10 years ? 50 ? However, "Because it’s there" is a worrying motivation to pursue this knowledge, because the pandora's box it opens is very real. We're getting closer to the point were we can play God and achieve magical technological feats. But are we mature enough to handle the powers that this technology bestows upon us ? Do we really need this technology now ?
- Terr_ 11y agoOften this topic makes me think of some of the fictional technology present in Deus Ex, released back in 2000, e.g: > The cells of every major tissue in the body of a nano-augmented agent are host to nanite-capsid "hybrids." These hybrids replicate in two stages: the viral stage, in which the host cell produces capsid proteins and packages them into hollowed viral particles, and the nanotech stage, in which the receiver-transmitter and CPU are duplicated and inserted into the protective viral coating. New RNA sequences are transmitted by microwave and translated in to plasmid vectors, resulting in a wholly natural and organic process.
- horsecaptin 11y agoHopefully they're not creating something airborne with an unending thirst for life.
- pak 11y agoThis article is self-contradictory. In the second caption: "Each cell of JCVI-syn3.0 contains just 473 genes, fewer than any other independent organism." In the main text: "In a 1995 Science paper, Venter’s team sequenced the genome of Mycoplasma genitalium, a sexually transmitted microbe with the smallest genome of any known free-living organism, and mapped its 470 genes." Which is it? Venter would have seemed to disproven his own claim to novelty, unless we've found new genes in M. genitalium's genome since 1995. Edit: As with most biological terms, part of the problem is the fuzziness of the definition of "gene". More recent studies claim M. genitalium has 525 genes [1], but that might be including tRNA and ncRNA regions. I'd still object to the article's poor editing. Also, let's get down to brass tacks here: we've only trimmed a 580kb genome down to 531kb (9% reduction). Clearly, life is already pretty damn efficient. [1] http://www.cell.com/cell/fulltext/S0092-8674(12)00776-3 http://www.cell.com/cell/fulltext/S0092-8674(12)00776-3
- greeneggs 11y agoThe figure caption is misleading. By "smallest genome" they mean fewest base pairs (531,000 base pairs, compared to 580,000 in Mycoplasma genitalium).
- pak 11y agoThat's not what I'm getting at. If M. genitalium really has only 470 genes by whatever counting scheme we've chosen, then the claim that "each cell of JCVI-syn3.0 contains just 473 genes, fewer than any other independent organism" is simply mistaken.
- marxidad 11y agoIt's possible that a different counting scheme was chosen for either case.
- dnautics 11y agoHey! So I worked in this lab (but on a different project): yeah some of the accounting is wierd and pr-ish, there are 530kb phytoplasmas (but they can't even make their own nucleotides) M.mycoides was used because it has a reasonable growing time (genitalium colonies appear in weeks)... So really the impressive achievement was generally strategically reducing a genome without doing much damage to the doubling time.