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The minimal cell: How is research coming on a simple, self-replicating “artificial” cell?


Such acell might shed some light on the origin of life, researchers hope. From Suzan Mazur at Oscillations:

Not to be outdone by Dutch, German and other Europeans now officially dabbling in synthetic cell research, America’s National Science Foundation has thrown its hat into the ring on funding synthetic cell development, per its April 18, 2018 letter to colleagues inviting proposals on the design and engineering of synthetic cells and cell components ($100K for relevant conferences, $300K re multicomponent subsystems, and up to $1M for research on the “pseudo-cell”). In May, following its call for proposals, NSF co-sponsored a synthetic and artificial cells roadmap meeting in Alexandria, Virginia with a handful of scientists already working in the field presenting and others in the audience looking to be educated.

Some highlights from a roundup of the May meeting:

As an engineer [Richard M.] Murray thinks replication is not so important in building a synthetic cell. Murray said it will be 30 years before the synthetic cell is developed and that no single lab can do it—it has to be a collaborative effort.

[Stanford bioengineers Drew] Endy considers the job 80% technical and 20% “anthropological”. He said making the cell would not be acheived just within academic circles. Endy also addressed motive in syncell development asking: “Are we simply going to invoke a name of building cells to do what we’re already doing?”

[University of Minnesota physicist Vincent Noireaux from 2014:] The ultimate goal of what we are doing is the minimal cell, but first we have to understand the relationship between information and self-organization. Where we are right now is that we have the most versatile and powerful cell-free transcription-translation system reported so far for synthetic biology applications.

Suzan Mazur: So time-wise where are you with development of a minimal cell that can self-reproduce?

Vincent Noireaux: It may be early to give an estimation of how many years. We have a system which we think is relatively close to a minimal cell. More.

Researchers keep discovering new systems in cells. Minimizing or obviating what has not yet been discovered is going to be a challenge…

See also: Suzan Mazur on mechanobiology, the next level of understanding of the cell

Cells are chock full of information systems, not just DNA


Origin of life: What we do and don’t know about the origin of life.

Is Dr Venter trying to create a biological cell completely from scratch? Last he worked on a host cell with a synthetic component. https://www.cnbc.com/2018/03/27/genome-pioneer-craig-venter-is-trying-to-decode-death.html jawa
Advances in biology and engineering have enabled the reprogramming of cells with well-defined functions, leading to the emergence of synthetic biology. https://www.researchgate.net/publication/6368005_A_synthetic_biology_challenge_Making_cells_compute [accessed Jul 19 2018]. Does “reprogramming” indicate that it was programmed before? How? jawa
three major challenges in synthetic biology https://www.creative-biolabs.com/blog/index.php/three-major-challenges-in-synthetic-biology/ jawa
Single Cell Analysis Challenge https://commonfund.nih.gov/singlecell/challenge jawa
Rules of Life (RoL): Design and Engineering of Synthetic Cells and Cell Components (DESYN-C3) https://nsf.gov/pubs/2018/nsf18071/nsf18071.jsp jawa
The symposium is fully dedicated to research on the bottom-up assembly of a functioning synthetic cell from its molecular components. Aim of this symposium is to bring together researchers worldwide to present and discuss the latest results in cutting-edge research on the synthetic cell, and its future scientific and technological perspectives. Further, the symposium aims at further building up on the community involved in this endeavour at the international level. http://www.syntheticcell.eu/2018/06/27/1st-international-symposium-on-building-a-synthetic-cell-basyc/ http://www.syntheticcell.eu/wp-content/uploads/2018/06/logo-basyc-international-symposium-3g-1024x735-768x551.jpg jawa
A synthetic cell that produces anti-cancer drugs within a tumor February 13, 2018 by Kevin Hattori, American Technion Society https://m.phys.org/news/2018-02-synthetic-cell-anti-cancer-drugs-tumor.html jawa
#2 bornagain77, Thanks for posting that information. jawa
#6 PeterA, Humpty Dumpty? jawa
#7 Otangelo Grasso: Very interesting comment. Thanks. jawa
LUCA—The Last Universal Common Ancestor 1 The last universal common ancestor represents the primordial cellular organism from which diversified life was derived http://reasonandscience.catsboard.com/t2176-lucathe-last-universal-common-ancestor minimal gene content of the first biological cell = 561 functional annotation descriptions = that means, it cannot be reduced further = irreducibly complex A minimal estimate for the gene content of the last universal common ancestor 19 December 2005 A truly minimal estimate of the gene content of the last universal common ancestor, obtained by three different tree construction methods and the inclusion or not of eukaryotes (in total, there are 669 ortholog families distributed in 561 functional annotation descriptions, including 52 which remain uncharacterized) A fairly complex genome similar to those of free-living prokaryotes, with a variety of functional capabilities including metabolic transformation, information processing, membrane/transport proteins and complex regulation, shared between the three domains of life, emerges as the most likely progenitor of life on Earth, with profound repercussions for planetary exploration and exobiology. The estimate of LUCA's gene content appears to be substantially higher than that proposed previously, with a typical number of over 1000 gene families, of which more than 90% are also functionally characterized.a fairly complex genome similar to those of free-living prokaryotes, with a variety of functional capabilities including metabolic transformation, information processing, membrane/transport proteins and complex regulation, shared between the three domains of life, emerges as the most likely progenitor of life on Earth. http://sci-hub.hk/https://www.sciencedirect.com/science/article/pii/S0923250805002676 The Last Universal Common Ancestor: emergence, constitution and genetic legacy of an elusive forerunner 2008 Jul 9 LUCA does not appear to have been a simple, primitive, hyperthermophilic prokaryote but rather a complex community of protoeukaryotes with a RNA genome, adapted to a broad range of moderate temperatures, genetically redundant, morphologically and metabolically diverse. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2478661/ The proteomic complexity and rise of the primordial ancestor of diversified life 2011 May 25 Life was born complex and the LUCA displayed that heritage. Recent comparative genomic studies support the latter model and propose that the urancestor was similar to modern organisms in terms of gene content https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123224/ Last Universal Common Ancestor had a complex cellular structure OCT 5, 2011 New evidence suggests that LUCA was a sophisticated organism after all, with a complex structure recognizable as a cell, researchers report. Their study appears in the journal Biology Direct. The study lends support to a hypothesis that LUCA may have been more complex even than the simplest organisms alive today, said James Whitfield, a professor of entomology at Illinois and a co-author on the study. http://news.illinois.edu/news/11/1005LUCA_ManfredoSeufferheld_JamesWhitfield_Caetano_Anolles.html Cenancestor, the Last Universal Common Ancestor 02 September 2012 Theoretical estimates of the gene content of the Last Common Ansestor’s genome suggest that it was not a progenote or a protocell, but an entity similar to extant prokaryotes. https://link.springer.com/article/10.1007/s12052-012-0444-8 Some Assembly Required: The Ingredients of Life July 1, 2017 From analyses of bacterial microfossils, (some of which may be up to 3.48 billion years old) we know that the most primitive life was nearly as complex as today’s bacteria. Unfortunately, the (micro)fossil record can’t really tell us how we got from the simple chemicals to living, working, bacterial cells. http://origins.case.edu/2017/07/01/some-assembly-required-the-ingredients-of-life/ Otangelo Grasso
Latemarch, Have you heard of Humpty Dumpty? PeterA
Gedankenexperiment: Take a half trillion bacteria in a nutrient broth. Gently sonicate until the cell walls are disrupted. Now you have the perfect warm pond. Nutrients, all the proteins, all the membranes, all the DNA and RNA. Now lets just wait around and see how long before the first cell emerges. Surely it should just self organize and burst quickly back to self replicating life......shouldn't it? I'm sorry maybe we should have set it all out in the sunlight so that the local entropy could be negative. Latemarch
bornagain77: Interesting information in your comment. Thanks. PeterA
Very interesting topic. PeterA
For a more realistic estimate of how far away we are from a a minimal cell that can self-reproduce, I suggest Dr. Tour's assessment of the situation:
An Open Letter to My Colleagues - James Tour - 2017 Excerpt: We synthetic chemists should state the obvious. The appearance of life on earth is a mystery. We are nowhere near solving this problem. The proposals offered thus far to explain life’s origin make no scientific sense. Beyond our planet, all the others that have been probed are lifeless, a result in accord with our chemical expectations. The laws of physics and chemistry’s Periodic Table are universal, suggesting that life based upon amino acids, nucleotides, saccharides and lipids is an anomaly. Life should not exist anywhere in our universe. Life should not even exist on the surface of the earth.17 http://inference-review.com/article/an-open-letter-to-my-colleagues James Tour is a synthetic organic chemist at Rice University. Origin of Life: An Inside Story - Professor James Tour – May 1, 2016 Excerpt: “All right, now let’s assemble the Dream Team. We’ve got good professors here, so let’s assemble the Dream Team. Let’s further assume that the world’s top 100 synthetic chemists, top 100 biochemists and top 100 evolutionary biologists combined forces into a limitlessly funded Dream Team. The Dream Team has all the carbohydrates, lipids, amino acids and nucleic acids stored in freezers in their laboratories… All of them are in 100% enantiomer purity. [Let’s] even give the team all the reagents they wish, the most advanced laboratories, and the analytical facilities, and complete scientific literature, and synthetic and natural non-living coupling agents. Mobilize the Dream Team to assemble the building blocks into a living system – nothing complex, just a single cell. The members scratch their heads and walk away, frustrated… So let’s help the Dream Team out by providing the polymerized forms: polypeptides, all the enzymes they desire, the polysaccharides, DNA and RNA in any sequence they desire, cleanly assembled. The level of sophistication in even the simplest of possible living cells is so chemically complex that we are even more clueless now than with anything discussed regarding prebiotic chemistry or macroevolution. The Dream Team will not know where to start. Moving all this off Earth does not solve the problem, because our physical laws are universal. You see the problem for the chemists? Welcome to my world. This is what I’m confronted with, every day.“ James Tour – leading Chemist https://uncommondesc.wpengine.com/intelligent-design/origin-of-life-professor-james-tour-points-the-way-forward-for-intelligent-design/
The 'simplest' cell ever found on earth is anything but 'simple:
Three Subsets of Sequence Complexity and Their Relevance to Biopolymeric Information - David L. Abel and Jack T. Trevors - Theoretical Biology & Medical Modelling, Vol. 2, 11 August 2005, page 8 "No man-made program comes close to the technical brilliance of even Mycoplasmal genetic algorithms. Mycoplasmas are the simplest known organism with the smallest known genome, to date. How was its genome and other living organisms' genomes programmed?" http://www.biomedcentral.com/content/pdf/1742-4682-2-29.pdf First-Ever Blueprint of 'Minimal Cell' Is More Complex Than Expected - Nov. 2009 Excerpt: A network of research groups,, approached the bacterium at three different levels. One team of scientists described M. pneumoniae's transcriptome, identifying all the RNA molecules, or transcripts, produced from its DNA, under various environmental conditions. Another defined all the metabolic reactions that occurred in it, collectively known as its metabolome, under the same conditions. A third team identified every multi-protein complex the bacterium produced, thus characterising its proteome organisation. "At all three levels, we found M. pneumoniae was more complex than we expected," http://www.sciencedaily.com/releases/2009/11/091126173027.htm To Model the Simplest Microbe in the World, You Need 128 Computers - July 2012 Excerpt: Mycoplasma genitalium has one of the smallest genomes of any free-living organism in the world, clocking in at a mere 525 genes. That's a fraction of the size of even another bacterium like E. coli, which has 4,288 genes.,,, The bioengineers, led by Stanford's Markus Covert, succeeded in modeling the bacterium, and published their work last week in the journal Cell. What's fascinating is how much horsepower they needed to partially simulate this simple organism. It took a cluster of 128 computers running for 9 to 10 hours to actually generate the data on the 25 categories of molecules that are involved in the cell's lifecycle processes.,,, ,,the depth and breadth of cellular complexity has turned out to be nearly unbelievable, and difficult to manage, even given Moore's Law. The M. genitalium model required 28 subsystems to be individually modeled and integrated, and many critics of the work have been complaining on Twitter that's only a fraction of what will eventually be required to consider the simulation realistic.,,, http://www.theatlantic.com/technology/archive/2012/07/to-model-the-simplest-microbe-in-the-world-you-need-128-computers/260198/ Microbe with stripped-down DNA may hint at secrets of life - Mar 24, 2016 Excerpt: The newly created bacterium has a smaller genetic code than does any natural free-living counterpart, with 531,000 DNA building blocks containing 473 genes. (Humans have more than 3 billion building blocks and more than 20,000 genes). But even this stripped-down organism is full of mystery. Scientists say they have little to no idea what a third of its genes actually do. "We're showing how complex life is, even in the simplest of organisms," researcher J. Craig Venter told reporters. "These findings are very humbling.",,, The genome is not some one-and-only minimal set of genes needed for life itself. For one thing, if the researchers had pared DNA from a different bacterium they would probably have ended up with a different set of genes.,,, The genome is "as small as we can get it and still have an organism that is ... useful," Hutchison said.,,, http://hosted.ap.org/dynamic/stories/U/US_SCI_SKINNY_GENES Minimal Cell Challenges Naturalism - March 26, 2016 Excerpt: “If we’re already playing God, we’re not doing a particularly good job of it,” Elfick says. “Simply streamlining what’s already in nature doesn’t seem very God-like and, if anything, is a very humbling exercise.” Venter also felt the humility vibes, according to Live Science: “We’re showing how complex life is even in the simplest of organisms,” said Craig Venter, founder and CEO of the J. Craig Venter Institute (JCVI), where the study was completed. “These findings are very humbling in that regard.” http://crev.info/2016/03/minimal-cell-challenges-naturalism/ Mycoplasma mycoides Just Destroyed Evolution “We’re Showing How Complex Life Is” – March 24, 2016 Excerpt: The origin of life problem can be divided into two broad categories: ground-up and top-down. In the ground-up approach, evolutionists try to figure out how the first life could have arisen spontaneously from an inorganic world. In spite of the evolutionist’s claims to the contrary, the century-long ground-up research program has utterly failed. That leaves the top-down approach. Here, evolutionists work with simple, unicellular life forms, carefully removing parts one at a time in their search for smaller, simpler life forms. If evolution is true, they should be able to reduce life to a very simple, basic form which could conceivably arise by chance somehow. This approach has been failing as well, as in recent years all the signs pointed to a minimal life form consisting of at least a few hundred genes—far beyond evolution’s meager resources of random change. Now, this latest research has upped the ante. It is just getting worse. A minimal organism consisting of 473 genes is many orders of magnitude beyond evolution’s capabilities. Simply put, the science contradicts the theory. What the science is telling us is that evolution is impossible, by any reasonable definition of that term. http://darwins-god.blogspot.com/2016/03/mycoplasma-mycoides-just-destroyed.html
It should be easy to come up with a self-replicating cell. After all, mindless, lifeless matter accidentally slopped itself into a self-replicating, metabolizing cell without even trying to. Surely today's scientists can easily do intentionally what stupid matter has done accidentally. ;o) harry

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