Artificial Genomes and Synthetic Organisms ABRINA, Joanna; ABUEL, Rachelle; BEA, Junelyn; CAFINO, Ernest; DALISAY, Roi;

PABILANE, Alma Biochem 121 Special Report Dr. Carillo REPORT OUTLINE (Guide to Reporter – NOT to be put in PowerPoint) I. Genetic Engineering A. Definition and Scope  Field of science that caters to the alteration of genetic code by artificial means, and is, therefore, different from traditional selective breeding (Dixon, February 2011)  Uses recombinant DNA or RNA techniques to introduce foreign, heritable material prepared in vitro or directly to the organism, and then fused or hybridized with the host  Human cloning (duplication of gene) and stem cell research are under genetic engineering  Forming new combinations of heritable genetic material followed by the incorporation of that material either indirectly through a vector system or directly through micro-injection, macroinjection and micro-encapsulation techniques.  TRANSGENIC - If genetic material from another species is added to the host  CISGENIC - if genetic material from the same species or a species that can naturally breed with the host is used  can also be used to remove genetic material from the target organism, creating a gene knockout organism  genetic engineering = gene manipulation + cell synthesis B. Applications and Examples  Insertion of human genes into sheep so that they secrete alpha-1 antitrypsin in their milk, a useful substance in treating some cases of lung disease  Combining the gene that programs poison in the tail of a scorpion with a cabbage forming genetically modified cabbages that kill caterpillars (poison as an insecticide)  Creating a chicken with four legs and no wings  Creating a goat with spider genes that creates "silk" in its milk (Dixon, February 2011)  One of the most popular and first breakthroughs of genetic engineering is the insulin-producing bacteria commercialized in 1982. II. Artificial/Synthetic Genomes A. Definition B. Process of Synthesis C. Artificial vs Synthetic III. Synthetic Organisms – products of genetic engineering and artificial genomes A. Examples a. Spider goats  Freckles, result of genetic engineering by Randy Lewis, a professor of Genetics at Utah State University  Freckles‘ milk is full of spider-silk protein.  ―In the medical field, we already know that we can produce spider silk that's good enough to be used in ligament repair. . . .we already know we can make it strong enough as an elastic. We've done some studies that show that you can put it in the body and you don't get inflammation and get ill.‖ – Randy Lewis\ b. Synthetic bacteria (unicellular organism) by J. Craig Venter  Synthia, aka Mycoplasma mycoides JCVI-syn 1.0, a cell which genetic code, copied and modified from an existing bacterium, had been assembled by a computer.  The genome of Mycoplasma mycoideswas constructed from more than 1,000 sections of preassembled units of DNA. Researchers transplanted the artificially assembled genome into a M. capricolum cell which had been

 Claims that synthetic biology is involved in creating artificial life. LS9 Inc. Nature medicine 7 (10): 1086–1090 . such as poliovirus and severe acute respiratory syndrome (SARS). Mass.  Environmental applications include functions such as detecting environmental contaminants using biosensors and removing such contaminants using specifically tailored plants or microorganisms. making them more accessible to those with no specialized training. medicines and even food.  Increasingly routine nature of many synthetic biology procedures.g. It has a $600 million contract with Exxon Mobil Corp. References:  Capecchi.  Industrial applications comprise employing plants. genetically modified organisms – either accidentally or deliberately – potentially resulting in harmful consequences for ecological systems and/or human health.. provided $30 million to fund experiments in synthetic biology.  Patenting strategies. Generating mice with targeted mutations. C. or plants. intellectual property and trade.emptied of its own genome. the bacteria began to function and reproduce in the same manner of naturally occurring M. a company founded by Dr. raising philosophical and religious concerns. microorganisms. but its synthetic genome was given an official version number. Social Issues . monitoring. mycoides  Not given new species name. as well as devising more efficient biomanufacturing and synthesis processes using chemical technology. providing capitals to start-up synthetic biology companies. Mycoplasma mycoides JCVI-syn1. potentially creating monopolies inhibiting basic research and restriction of product development to only large companies. D. animals. agribusiness and chemical companies are already big funders of synthetic biology research. in San Francisco.—are working on synthetic cells to produce renewable fuels. production of the antimalarial drug artemisinin in genetically engineered bacteria rather than extracting it from a plant source).  Trade and global justice issues. It also owns the intellectual-property rights to cell-creation techniques. Current Development  Synthetic Genomics Inc. (2001). Venter. bio-plastics. and responding to disease conditions in humans and animals and developing and manufacturing new drugs and vaccines.  Possibility of recreation existing. Benefits and Uses  The U.  Health-related applications include diagnosing. R. diesel.  The possible exploitation of synthetic biology for bioterrorism – including the construction of modified or novel microorganisms with lethal or incapacitating effects: synthesis of several pathogenic viruses from scratch. biosecurity. and Joule Unlimited in Cambridge. to schemean algae that can capture carbon dioxide and make fuel. and ethical concerns. and jet fuel. or eradicated pathogens of humans. industrial chemicals.0. Calif. Emerging risks are classified into 4 headings: biosafety.Many concerns have arisen about the dangers of synthetic biology. M. Some of these issues include:  The release into the environment of novel. extinct.  Proponents hope this emerging field will create a new "bioeconomy" in which any and all types of plant matter can feed synthetic organisms that will be "living factories" that can be used for production fuels.S. government together with the leading oil.. and specifically tailored enzymes for developing biofuels. Once the DNA "booted up". such as preventing exploitation of indigenous resources by enabling chemical synthesis of valuable products in industrial countries (e.  Green energy companies are using the emerging field of synthetic biology to modify bacteria into creating hydrocarbons for gasoline.  At least three other companies—Amyris Biotechnologies in Emeryville. B.

(12 February 2011). Schouten.guardian.co. a company Dr. sequencing the 1-million-base genome of the faster growing M. The team decided to change microbes in midstream. P. Upsides hitherto.e. partly due to slow growth of M. Smith. and researchers found they could delete 100 individual genes without ill effect However. H. a New Tool for Traditional Plant Breeding. But these steps have taken years because the technology to make and manipulate whole chromosomes did not exist. and San Diego. Venter John Craig Venter and his team at the J. these steps became bogged down. modify the bacterial genome. page 17 http://www. The project was achieved at great expense.com Jacobsen. Craig Venter Institute (JCVI) in Rockville. p. Potato Research 51: 75–88 The European Parliament and the council of the European Union (12 March 2001). vaccines) getting them to ―boot‖ up the same way in a cell Timeline of the Artificial Genome Project 1995 John Craig Venter and JCVI colleagues Clyde Hutchison III and Hamilton Smith sequenced the 600.foe. 2009 They showed they could extract the M.000-base chromosome of a bacterium called Mycoplasma genitalium.html http://www. an estimated $40 million (most of it paid for by Synthetic Genomics.com/6486-live-organism-synthetic-genome-created. Maryland. (2008). genitalium that one experiment can take weeks to complete. and then transfer it to a close microbial relative.livescience. mycoidesand beginning to build a synthetic copy of its chromosome.org/newfrontiers/lowrie. Cisgenesis. place it into yeast. the smallest genome of a free-living organism. Official Journal of the European Communities. 2007 Venter. M. Should be Exempted from the Regulation on Genetically Modified Organisms in a Step by Step Approach.actionbioscience. the largest piece of DNA synthesized (~a million units in length) able to make it accurate enough to substitute for the cell‘s own DNA Dissuasion designing new organisms will take years progress toward making biofuels is already being achieved with conventional genetic engineering approaches in which existing organisms are modified a few genes at a time further research should be halted until sufficient regulations are in place. J. ones that make fuels or pharmaceuticals. and colleagues finally demonstrated that they could transplant natural chromosomes from one microbial species to another 2008 They showed that they could make an artificial chromosome that matched M. as such may pose ―dangerous new technology‖ Further Goals: Creating heavily customized genomes (i.synbioproject. Venter founded) and effort of 20 people working for almost 15 years.globalchange.org/topics/synbio101/links/ ―The first self-replicating species we‘ve had on the planet whose parent is a computer. E. successfully created the first living organism with a completely synthetic genome..html http://www. capricolum . The microbe has about 500 genes. synthesizing a full bacterial chromosome and making it to work in a recipient cell are needed in order to confirm the minimal genome suggested by those experiments.uk/science/2012/jan/14/synthetic-biology-spider-goat-genetics http://www. mycoidesnatural chromosome.‖ –Dr. genitalium‘s but also contained ―watermark‖ DNA sequences that would enable them to tell the synthetic genome from the natural one However. Directive on the release of genetically modified organisms (GMOs) Directive 2001/18/EC ANNEX.org/projects/food-and-technology/synthetic-biology http://www.        Dixon. Hutchison. Genetic engineering: what is genetic engineering? Retrieved from www.

mycoidesas well. S. Researchers say they created ‗Synthetic cell‘. alter it on the computer to add or delete genes. Retrieved from 6486-live-organism. When translated.080 base pairs.com Figure 1. mycoides genome. the DNA strands came together in runs of tens of thousands of base pairs. 958-959 Bourzac. MIT.080. In the course of the project. Once the DNA "booted up. When the artificial genome entered the cell. a single base pair mistake set the entire program back three months. capricolum host cells. which still contain certain machinery that let them carry out the process of expressing a gene.21cell/NYTimes. or taking the genetic code and using it to build proteins (transcription). they found out that even a tiny inaccuracy could prevent the inert DNA from activating into a live bacterium. ordered from Blue Heron. They transplanted the artificially assembled genome—named Mycoplasma mycoides JCVI-syn1. But DNA sequencing accuracy has become so advanced that at least finding the mistakes took only days. The scientists start off with a genome sequence from a bacterium that already has a very small genome. the watermarks spell out the names of the 46 researchers who helped with the project. and began doing their job." the bacteria began to function and reproduce in the same manner as naturally occurring M. a company that specializes in synthesizing DNA. mycoides.000-base-pair synthetic genome.htm Fox. N. the cellular machines that run DNA transcription recognized the DNA. Retrieved from http://www.The bacterial colonies growing on these petri dishes contain a genome modified on a computer and then pieced together in the lab . At one point. How to make an artificial cell: Researchers at the Venter Institute explain their groundbreaking techniques. Science Magazine. Retrieved from http://www. The watermarks contain a code that translates DNA into English letters with punctuation. and see how the changes affect the cell's function. allowing the scientists to literally write messages with the genes. Sources: (2010). Slowly. Booting up results once the recombinant DNA utilizes elements of the M. each containing 1. For the assembled genome to be recognizable as synthetic. each section of DNA contained 80 base pairs at every end that instructed the yeast where to join the two strands. and a URL that anyone who deciphers the code can e-mail. (2010). 328. Technology Review. mycoidesrather than M capricolum. then synthesize it from chemicals. The colony grew like a typical M. K. However. (2010). Robert Oppenheimer. and the microbes were indeed making proteins characteristic of M.syntheticgenome-created. the researchers deliberately inserted four sequences of DNA that serve as watermarks. 2012 Wade. To assist in assembly. and then hundreds of thousands.000 sections of preassembled units of DNA. Synthetic genome brings new life to bacterium. quotations from James Joyce.0—into a Mycoplasma capricolum cell that had been emptied of its own genome. The researchers used yeast to glue together thousands of DNA snippets. First live organism with synthetic genome created. until the yeast produced a complete 1. (2010). they successfully transplanted the recombinant genome in M capricolum. The scientists constructed the genome of the bacterium Mycoplasma mycoides from more than 1. The New York Times.How to Make an Artificial Cell Technology Review. physicist Richard Feynman and J. They sequenced the DNA in the blue bacterial colonies they had retrieved and later on confirmed that the bacteria had the synthetic genome. the synthesis process still introduced some mutations into the M.com on March 15. transplant it into a cell.2010 After numerous attempts. not the months needed a decade ago during the infancy of genetic engineering.

Self-replicatingM.Figure 2.mycoides bacteria revealed in an electron micrograph .Blue colonies of Mycoplasma mycoidesindicate a successfully transplanted genome Figure 3.

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