Synthetic biology

Synthetic biology

Synthetic biology is an interdisciplinary science, combining disciplines such as biotechnology, evolutionary biology, molecular biology, systems biology and biophysics.

The definition of synthetic biology is heavily debated not only among natural scientists but also in the human sciences, arts and politics.[1] One popular definition is "designing and constructing biological devices[2] and biological systems for useful purposes." However, the functional aspects of this definition stem from molecular biology and biotechnology.[3]

Contents

  • History 1
  • Perspectives 2
    • Engineering 2.1
    • Re-writing 2.2
  • Key enabling technologies 3
    • Standardized DNA parts 3.1
    • DNA synthesis 3.2
    • DNA sequencing 3.3
    • Modeling 3.4
  • Examples 4
    • Synthetic DNA 4.1
    • Synthetic life 4.2
    • Information Storage 4.3
    • Synthetic genetic pathways 4.4
    • Unnatural nucleotides and amino acids 4.5
    • Reduced amino-acid libraries 4.6
    • Designed proteins 4.7
    • Biosensors 4.8
    • Materials production 4.9
  • Bioethics and security issues 5
    • Opposition to synthetic biology 5.1
  • See also 6
  • References 7
  • External links 8

History

The term "synthetic biology" has a history spanning the twentieth century. The first use was in Stéphane Leducs’s publication of « Théorie physico-chimique de la vie et générations spontanées » (1910)[4] and « La Biologie Synthétique » (1912).[5] In 1974, the Polish geneticist Wacław Szybalski used the term "synthetic biology",[6] writing:

Let me now comment on the question "what next". Up to now we are working on the descriptive phase of molecular biology. ... But the real challenge will start when we enter the synthetic phase of research in our field. We will then devise new control elements and add these new modules to the existing genomes or build up wholly new genomes. This would be a field with an unlimited expansion potential and hardly any limitations to building "new better control circuits" or ..... finally other "synthetic" organisms, like a "new better mouse". ... I am not concerned that we will run out of exciting and novel ideas, ... in the synthetic biology, in general.

When in 1978 the Nobel Prize in Physiology or Medicine was awarded to Arber, Nathans and Smith for the discovery of restriction enzymes, Wacław Szybalski wrote in an editorial comment in the journal Gene:

The work on restriction nucleases not only permits us easily to construct recombinant DNA molecules and to analyze individual genes, but also has led us into the new era of synthetic biology where not only existing genes are described and analyzed but also new gene arrangements can be constructed and evaluated.[7]

Perspectives

Engineering

Engineers view biology as a technology – the systems biotechnology or systems biological engineering.[8] Synthetic Biology includes the broad redefinition and expansion of biotechnology, with the ultimate goals of being able to design and build engineered biological systems that process information, manipulate chemicals, fabricate materials and structures, produce energy, provide food, and maintain and enhance human health (see Biomedical Engineering) and our environment.[9]

Studies in synthetic biology can be subdivided into broad classifications according to the approach they take to the problem at hand: standardization of biological parts, biomolecular engineering, genome engineering, and biomolecular design. Biomolecular engineering includes approaches which aim to create a toolkit of functional units that can be introduced to present new orthogonal functions in living cells.

  • syntheticbiology.org the original community website
  • Synthetic biology books recent popular science book and textbooks
  • Biobuilder.org an educational website to engage and inform a wider audience of synthetic biology enthusiasts
  • Synthetic Biology Engineering Research Center (SynBERC) A NSF-funded multi-university effort to lay the foundations for synthetic biology.
  • BioBricks Foundation president Drew Endy; organization related to iGEM
  • The (World) Associates for Biosystem Science and Engineering (WABSE)
  • Synthetic Biology Project Synthetic biology news, events, publications and more.
  • International Association Synthetic Biology
  • Synbiosafe European project to research the safety and ethical aspects of synthetic biology.
  • Introductory Summary of Synthetic Biology Concise overview of synthetic biology concepts, developments and applications
  • Collaborative overview article on Synthetic Biology
  • [1] Official notes from the 2014 CBD COP12 Conference

External links

  1. ^ "Synthetic biology: promises and perils of modern biotechnology". Marsilius Academy Heidelberg - Summer school. Heidelberg University. Retrieved 2014-09-11. 
  2. ^ "Registry of Standard Biological Parts". Retrieved 2014-09-11. 
  3. ^ "Synthetic-biology firms shift focus". Nature.  
  4. ^ Théorie physico-chimique de la vie et générations spontanées, S. Leduc,1910
  5. ^ Leduc, Stéphane (1912). Poinat, A., ed. La biologie synthétique, étude de biophysique. 
  6. ^ Wacław Szybalski, In Vivo and in Vitro Initiation of Transcription, Page 405. In: A. Kohn and A. Shatkay (Eds.), Control of Gene Expression, pp. 23–4, and Discussion pp. 404–5 (Szybalski's concept of Synthetic Biology), 411–2, 415–7. New York: Plenum Press, 1974
  7. ^ Szybalski, W; Skalka, A (November 1978). "Nobel prizes and restriction enzymes". Gene 4 (3): 181–2.  
  8. ^ Zeng, Jie (Bangzhe). On the concept of systems bio-engineering. Coomunication on Transgenic Animals, June 1994, CAS, PRC. [cited 1994-06-05];6.
  9. ^ Chopra, Paras; Akhil Kamma. "Engineering life through Synthetic Biology". In Silico Biology 6. Retrieved 2008-06-09. 
  10. ^ Channon, Kevin; Bromley, Elizabeth HC; Woolfson, Derek N (August 2008). "Synthetic Biology through Biomolecular Design and Engineering". Current Opinion in Structural Biology 18 (4): 491–8.  
  11. ^ Stone, M (2006). "Life Redesigned to Suit the Engineering Crowd". Microbe 1 (12): 566–570. 
  12. ^ Group, Bio FAB; Baker D; Church G; Collins J; Endy D; Jacobson J; Keasling J; Modrich P; Smolke C; Weiss R (June 2006). "Engineering life: building a fab for biology".  
  13. ^ a b P. S. Freemont and R. I. Kitney, Editors "Synthetic Biology - A Primer". World Scientific. 2012.  
  14. ^ "Tom Knight (2003). Idempotent Vector Design for Standard Assembly of Biobricks". Retrieved 2014-09-26. 
  15. ^ Pollack, Andrew (2007-09-12). "How Do You Like Your Genes? Biofabs Take Orders". The New York Times.  
  16. ^ Forster, AC; Church GM. (2006-08-22). "Towards synthesis of a minimal cell". Mol Syst Biol. 2 (1): 45.  
  17. ^ Rollie et al. (2012). "Designing biological systems: Systems Engineering meets Synthetic Biology". Chemical Engineering Science 69: 1–29.  
  18. ^ Kaznessis YN (2007). "Models for synthetic biology". BMC Systems Biology 1: 47.  
  19. ^ Kosuri, S. and Church, G.M. (2014). "Large-scale de novo DNA synthesis: technologies and applications". Nature Methods 11 (5): 499–507.  
  20. ^ Blight KJ, Kolykhalov AA, Rice CM. (2000-12-08). "Efficient initiation of HCV RNA replication in cell culture". Science 290 (5498): 1972–4.  
  21. ^ Couzin J (2002). "Virology. Active poliovirus baked from scratch". Science 297 (5579): 174–5.  
  22. ^ Smith, Hamilton O.; Clyde A. Hutchison; Cynthia Pfannkoch; J. Craig Venter (2003-12-23). "Generating a synthetic genome by whole genome assembly: {phi}X174 bacteriophage from synthetic oligonucleotides". Proc. Natl. Acad. Sci. U.S.A. 100 (26): 15440–5.  
  23. ^ Wade, Nicholas (2007-06-29). "Scientists Transplant Genome of Bacteria". The New York Times.  
  24. ^ Gibson, DG; Benders GA, Andrews-Pfannkoch C, Denisova EA, Baden-Tillson H, Zaveri J, Stockwell TB, Brownley A, Thomas DW, Algire MA, Merryman C, Young L, Noskov VN, Glass JI, Venter JC, Hutchison CA 3rd, Smith HO. (2008-01-24). "Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome". Science 319 (5867): 1215–20.  
  25. ^ "Scientists Reach Milestone On Way To Artificial Life". 2010-05-20. Retrieved 2010-06-09. 
  26. ^ Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA 3rd, Smith HO, Venter JC. (2010). "Creation of a bacterial cell controlled by a chemically synthesized genome". Science 329 (5987): 52–6.  
  27. ^ a b c d e Robert Lee Hotz (May 21, 2010). "Scientists Create First Synthetic Cell". The Wall Street Journal. Retrieved April 13, 2012. 
  28. ^ Craig Venter Institute. "FAQ". Retrieved 2011-04-24. 
  29. ^ W. Wayte Gibbs (May 2004). "Synthetic Life". Scientific American. 
  30. ^ "NOVA: Artificial life". Retrieved 2007-01-19. 
  31. ^ Church, G.M. et al. (2012). "Next-Generation Digital Information Storage in DNA". Science 337 (6102): 1628.  
  32. ^ "Huge amounts of data can be stored in DNA". Sky News. 23 January 2013. Retrieved 24 January 2013. 
  33. ^ Pollack, Andrew (May 7, 2014). "Researchers Report Breakthrough in Creating Artificial Genetic Code".  
  34. ^ Callaway, Ewen (May 7, 2014). "First life with 'alien' DNA".  
  35. ^ Malyshev, Denis A.; Dhami, Kirandeep; Lavergne, Thomas; Chen, Tingjian; Dai, Nan; Foster, Jeremy M.; Corrêa, Ivan R.; Romesberg, Floyd E. (May 7, 2014). "A semi-synthetic organism with an expanded genetic alphabet".  
  36. ^ Davidson, AR., Lumb, KJ., Sauer, RT. (1995). "Cooperatively folded proteins in random sequence libraries". Nature Structural Biology 2 (10): 856–864.  
  37. ^ Kamtekar, S, Schiffer, J., Xiong, H., Babik, J., Hecht, M. (1993). "Protein design by binary patterning of polar and nonpolar amino acids". Science 262 (5140): 1680–1685.  
  38. ^ Walter, K.U., Vamvaca, K., Hilvert, D (2005). "An active enzyme constructed from a 9-amino acid alphabet". The Journal of Biological Chemistry 280 (45): 37742–6.  
  39. ^ Koder, RL., et al. (2009). "Design and engineering of an O(2) transport protein". Nature 458 (7236): 305–9.  
  40. ^ Farid, TA., Kodali, G., Solomon, LA., et al. (2013). "Elementary tetrahelical protein design for diverse oxidoreductase functions". Nature chemical biology 9 (12): 826–33.  
  41. ^ Armbruster BN, Li X, Pausch MH, Herlitze S, Roth BL. (2007). "Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand". PNAS USA 104 (12): 5163–8.  
  42. ^ Gibbs, W. Wayt (1997). "Critters on a Chip". Scientific American. Retrieved 2 Mar 2009. 
  43. ^ Nguyen, Peter; Botyanszki, Zsofia; Tay, Pei-Kun; Joshi, Neel (Sep 17, 2014). "Programmable biofilm-based materials from engineered curli nanofibres". Nature Communications 5: 4945.  
  44. ^ a b Bügl, H. et al. (2007). "DNA synthesis and biological security". Nature Biotechnology 25 (6): 627–629.  
  45. ^ a b Presidential Commission for the study of Bioethical Issues, December 2010 NEW DIRECTIONS The Ethics of Synthetic Biology and Emerging Technologies Retrieved 2012-04-14.
  46. ^ SYNBIOSAFE official site
  47. ^ Schmidt M, Ganguli-Mitra A, Torgersen H, Kelle A, Deplazes A, Biller-Andorno N (2009). "A priority paper for the societal and ethical aspects of synthetic biology" (PDF). Systems and Synthetic Biology 3 (1–4): 3–7.  
  48. ^ Schmidt M. Kelle A. Ganguli A, de Vriend H. (Eds.) 2009. "Synthetic Biology. The Technoscience and its Societal Consequences". Springer Academic Publishing.
  49. ^ Kelle A (2009). "Ensuring the security of synthetic biology—towards a 5P governance strategy" (PDF). Systems and Synthetic Biology 3 (1–4): 85–90.  
  50. ^ Schmidt M (2008). "Diffusion of synthetic biology: a challenge to biosafety" (PDF). Systems and Synthetic Biology 2 (1–2): 1–6.  
  51. ^ COSY: Communicating Synthetic Biology
  52. ^ Kronberger, N; Holtz, P; Kerbe, W; Strasser, E; Wagner, W (2009). "Communicating Synthetic Biology: from the lab via the media to the broader public" (PDF). Systems and Synthetic Biology 3 (1–4): 19–26.  
  53. ^ Cserer A, Seiringer A (2009). "Pictures of Synthetic Biology: A reflective discussion of the representation of Synthetic Biology (SB) in the German-language media and by SB experts" (PDF). Systems and Synthetic Biology 3 (1–4): 27–35.  
  54. ^ COSY/SYNBIOSAFE Documentary
  55. ^ Report of IASB "Technical solutions for biosecurity in synthetic biology", Munich, 2008.
  56. ^ Parens E., Johnston J., Moses J. Ethical Issues in Synthetic Biology. 2009.
  57. ^ NAS Symposium official site
  58. ^ Presidential Commission for the study of Bioethical Issues, December 2010 FAQ
  59. ^ Katherine Xue for Harvard Magazine. September–October 2014 Synthetic Biology’s New Menagerie
  60. ^ Yojana Sharma for Scidev.net March 15, 2012. NGOs call for international regulation of synthetic biology
  61. ^ The New Synthetic Biology: Who Gains? (2014-05-08), Richard C. Lewontin, New York Review of Books

References

See also

On March 13, 2012, over 100 environmental and civil society groups, including human genome or human microbiome.[59][60] Richard Lewontin wrote that some of the safety tenets for oversight discussed in The Principles for the Oversight of Synthetic Biology are reasonable, but that the main problem with the recommendations in the manifesto is that "the public at large lacks the ability to enforce any meaningful realization of those recommendations."[61]

Opposition to synthetic biology

After the publication of the first synthetic genome by Craig Venter's group and the accompanying media coverage about "life" being created, President Obama requested the Presidential Commission for the Study of Bioethical Issues to study synthetic biology.[58] The commission convened a series of meetings, then issued a report in December 2010 titled "New Directions: The Ethics of Synthetic Biology and Emerging Technologies." The report clarified that the Venter group had not created life, and noted that synthetic biology is an emerging field, which creates potential risks and rewards. The commission did not recommend any changes to policy or oversight and called for continued funding of the research and new funding for monitoring, study of emerging ethical issues, and public education.[45]

On July 9–10, 2009, the National Academies' Committee of Science, Technology & Law convened a symposium on "Opportunities and Challenges in the Emerging Field of Synthetic Biology".[57]

In January 2009, the Alfred P. Sloan Foundation funded the Woodrow Wilson Center, the Hastings Center, and the J. Craig Venter Institute to examine the public perception, ethics, and policy implications of synthetic biology.[56]

An initiative for self-regulation has been proposed by the International Association Synthetic Biology[55] that suggests some specific measures to be implemented by the synthetic biology industry, especially DNA synthesis companies. In 2007, a group led by scientists from leading DNA synthesis companies published a "practical plan for developing an effective oversight framework for the DNA-synthesis industry."[44]

COSY is another European initiative - its focus is on public perception and communication of synthetic biology.[51][52][53] To better communicate synthetic biology and its societal ramifications to a broader public, COSY and SYNBIOSAFE published a 38-minute documentary film in October 2009.[54]

The European Union funded project SYNBIOSAFE[46] has issued several reports on how to manage the risks of synthetic biology. A 2007 paper identified key issues in the areas of safety, security, ethics and the science-society interface (the latter of which they defined as public education and as ongoing dialogue among scientists, businesses, government, and ethicists).[47][48] Key security issues involved engaging companies that sell synthetic DNA and the artemisinin), it may also lead to synthesis or redesign of harmful pathogens (e.g., smallpox) by malicious actors.[49] The bio-hacking community remains a source of special concern, as the distributed and diffuse nature of open-source biotechnology makes it difficult to track, regulate, or mitigate potential biosafety and biosecurity concerns.[50]

In addition to numerous scientific and technical challenges, synthetic biology raises ethical issues and biosecurity issues. However, with the exception of regulating DNA synthesis companies,[44] the issues are not seen as new because they were raised during the earlier recombinant DNA and genetically-modified organism (GMO) debates and there were already extensive regulations of genetic engineering and pathogen research in place in the U.S.A., Europe and the rest of the world.[45]

Bioethics and security issues

By integrating synthetic biology approaches with materials sciences, it would be possible to envision cells as microscopic molecular foundries to produce materials with properties that can be genetically encoded. Recent advances towards this include reengineering curli fibers, the amyloid component of extracellular material of biofilms, as a platform for a programmable nanomaterial. These nanofibers have been genetically programmed for specific functions, including adhesion to substrates, nanoparticle templating, and protein immobilization.[43]

Materials production

A Lux operon of Aliivibrio fischeri. The Lux operon consists of five genes which are necessary and sufficient for bacterial bioluminescence, and can be placed under an alternate promoter to express the genes in response to an arbitrary environmental stimulus. One such sensor created in Oak Ridge National Laboratory and named “critter on a chip” used a coating of bioluminescent bacteria on a light sensitive computer chip to detect certain petroleum pollutants. When the bacteria sense the pollutant, they begin to generate light.[42]

Biosensors

While there are methods to engineer natural proteins (such as by Directed evolution), there are also projects to design novel protein structures that match or improve on the functionality of existing proteins. One group generated a helix bundle that was capable of binding oxygen with similar properties as hemoglobin, yet did not bind carbon monoxide.[39] A similar protein structure was generated to support a variety of oxidoreductase activities.[40] Another group generated a family of G-protein coupled receptors which could be activated by the inert small molecule clozapine-N-oxide but insensitive to the native ligand (acetylcholine)[41]

Designed proteins

Researchers have investigated the structure and function of proteins by reducing the normal set of 20 amino acids, that is, by generating proteins where certain groups of amino acids may be substituted with a single amino acid.[36] For instance, several non-polar amino acids within a protein may all be replaced with a single non-polar amino acid.[37] One project demonstrated that an engineered version of Chorismate mutase still had catalytic activity when only 9 amino acids were used.[38]

Reduced amino-acid libraries

Many technologies have been developed for incorporating unnatural nucleotides and amino acids into nucleic acids and proteins, both in vitro and in vivo. For example, in May 2014, researchers announced that they had successfully introduced two new artificial nucleotides into bacterial DNA, and by including individual artificial nucleotides in the culture media, were able to passage the bacteria 24 times; they did not create mRNA or proteins able to use the artificial nucleotides.[33][34][35]

Unnatural nucleotides and amino acids

Traditional metabolic engineering has been bolstered by the introduction of combinations of foreign genes and optimization by directed evolution. Perhaps the best known application of synthetic biology to date is engineering E. coli and yeast for commercial production of a precursor of the antimalarial drug, Artemisinin, by the laboratory of Jay Keasling.

Synthetic genetic pathways

Scientists can encode vast amounts of digital information onto a single strand of Mb of data from the book is more than 1000 times greater than the previous largest amount of information to be stored in synthesized DNA.[31] A similar project had encoded the complete sonnets of William Shakespeare in DNA.[32]

Information Storage

One important topic in synthetic biology is synthetic life, that is, [29] Researchers involved stated that the creation of "true synthetic biochemical life" is relatively close in reach with current technology and cheap compared to the effort needed to place a man on the Moon.[30]

Synthetic life

Driven by dramatic decreases in costs of making oligonucleotides ("oligos"), the sizes of DNA constructions from oligos have increased to the genomic level.[19] For example, in 2000, researchers at Washington University reported synthesis of the 9.6 kbp (kilo base pair) Hepatitis C virus genome from chemically synthesized 60 to 80-mers.[20] In 2002 researchers at SUNY Stony Brook succeeded in synthesizing the 7741 base poliovirus genome from its published sequence, producing the second synthetic genome. This took about two years of work.[21] In 2003 the 5386 bp genome of the bacteriophage Phi X 174 was assembled in about two weeks.[22] In 2006, the same team, at the J. Craig Venter Institute, had constructed and patented a synthetic genome of a novel minimal bacterium, Mycoplasma laboratorium and were working on getting it functioning in a living cell.[23][24]

Synthetic DNA

Examples

Models inform the design of engineered biological systems by allowing synthetic biologists to better predict system behavior prior to fabrication. Synthetic biology will benefit from better models of how biological molecules bind substrates and catalyze reactions, how DNA encodes the information needed to specify the cell and how multi-component integrated systems behave. Recently, multiscale models of gene regulatory networks have been developed that focus on synthetic biology applications. Simulations have been used that model all biomolecular interactions in transcription, translation, regulation, and induction of gene regulatory networks, guiding the design of synthetic systems.[18]

Modeling

[17]

DNA sequencing

In 2007 it was reported that several companies were offering the Anthony Forster's synthetic cell projects.)[16] This favors a synthesis-from-scratch approach.

DNA synthesis

The most used[13]:22–23 standardized DNA parts are BioBrick plasmids invented by Tom Knight in 2003.[14] Biobricks are stored at the Registry of Standard Biological Parts in Cambridge, Massachusetts and the BioBrick standard has been used by thousands of students worldwide in the international Genetically Engineered Machine (iGEM) competition.[13]:22–23

Standardized DNA parts

There are several key enabling technologies that are critical to the growth of synthetic biology. The key concepts include standardization of biological parts and hierarchical abstraction to permit using those parts in increasingly complex synthetic systems.[12] Achieving this is greatly aided by basic technologies of reading and writing of DNA (sequencing and fabrication), which are improving in price/performance exponentially (Kurzweil 2001). Measurements under a variety of conditions are needed for accurate modeling and computer-aided-design (CAD).

Key enabling technologies

Re-writers are synthetic biologists who are interested in testing the idea that since natural biological systems are so complicated, we would be better off re-building the natural systems that we care about, from the ground up, in order to provide engineered surrogates that are easier to understand and interact with.[11] Re-writers draw inspiration from refactoring, a process sometimes used to improve computer software.

Re-writing

[10]