CH391L/S13/Introduction

Introduction to Synthetic Biology

This quotation about the Molecular Biology revolution of the first part of the twentieth century sets the stage for synthetic biology.

It was a quarter-century ago that Watson and Crick, playing with cardboard cutouts and wire-and-sheet-metal models and sorting out the few controlling facts from a hotchpotch of data, elucidated the molecular architecture of the genetic material itself, the double-railed circular staircase of deoxyribonucleic acid. What has been learned in the years since is full of surprises, full of wit and beauty, full of the most gratifying illumination. The culmination is now approaching of the great endeavor of biology that has swept on for a century and a quarter—an achievement of imagination that rivals the parallel, junior enterprise in physics that began with relativity and quantum mechanics. Biologists' pursuit of complete and explicit understanding has begun to list the exact molecular sequences that encode the hereditary message, instruction by instruction; it has tweezed apart the springs and gears by which the message is expressed in the building of the cell, and the ratchets and pawls by which that expression is regulated; it has accustomed men to speak apparently without wonder of the structural transformations by which a single protein molecule, an enzyme, will break or build other proteins, or by which, for example, a molecule of hemoglobin will flex its broad shoulders and bend its knees to pick up oxygen.

To be sure, the discoveries have not produced the great practical payout that has repeatedly been anticipated for them. Biologists have no atomic power stations and no bombs to point to, or at least not yet. No baby has been cured of a congenital deficiency by insertion of a missing gene into its cells. There is no vaccine against human leukemia, not even a cure for hay fever. Though some of the rewards are at last imminent, most scientists have learned that they must speak guardedly and emphasize to laymen the gaps to be filled in.

The Eighth Day of Creation, Horace Freeland Judson, 1979 [1]

The Culture of Synthetic Biology

On the one hand, synthetic biology has its roots in conventional fields of science, including molecular biology, metabolic engineering, protein design, and bioengineering. One could say that it is simply a clever re-branding of advances in those fields. On the other hand, much of the "newness" of synthetic biology has been due to the impact of a do-it-yourself (DIY) mindset associated with the open-source movement and even hacker culture that is not traditional to the field of molecular biology. The idea is that putting the tools in the hands of young and creative scientists will result in rapid and creative progress. This is a philosophy of the iGEM competition, for example. Critics of this approach would contend that such rapid progress and wide dissemination of these technologies without oversight risks having unintended adverse ecological and societal impacts. See the synthetic biology ethics topic.

Links related to the flavor and hype of synthetic biology:

• Adventures in Synthetic Biology Comic Book
• SEED Magazine's Synthetic Biology Cribsheet
• Field Test Film Core Synthetic Biology documentary
• 2008 TED talk given by J.Craig Venter about the 1st Synthetic Genome Assembled
• Imperial College iGEM team Wellcome Trust documentary (50 min)
• E. chromi video
• iGEM memes

Timeline of Synthetic Biology

Year	Event
1970	Discovery of first site-specific restriction enzyme [2]
1972	First publication on recombinant DNA [3]
1976	First genome sequenced- Bacteriophage MS2 [4]
1981	Introduction of phosphoramidite method of DNA oligonucleotide synthesis. [5]
1983	First genetically modified plant is produced [6]
2000	The "Repressilator" [7]
2002	Creation of the first synthetic virus [8]
2003	First use of the term "BioBrick" [9] First chemically synthesized bacteriophage genome assembled [10]
2004	First iGEM Jamboree
2005	"Adventures in Synthetic Biology" Nature Cover
2006	Human Genome Project completed [11]
2007	First application of context-free grammars in CAD software for Synthetic Biology (GenoCAD) [12]
2008	First synthetic genome assembled [13]
2010	Creation of Mycoplasma mycoides JCVI-syn1.0, the first microbe with a self-replicating synthetic genome. [14]
2012	Storage of digital information using DNA popularized in the media, Economist (Archives Could Last Thousands of Years when Stored on DNA)

What is synthetic biology?

Types of studies referred to as synthetic biology (and other fields that might also claim them).

• "The goal of synthetic biology is to extend or modify the behavior of organisms and engineer them to perform new tasks."[15]
• "Synthetic biologists come in two broad classes. One uses unnatural molecules to reproduce emergent behaviours from natural biology, with the goal of creating artificial life. The other seeks interchangeable parts from natural biology to assemble into systems that function unnaturally." [16]
• Bottom-up assembly of genes, organelles and organisms.
  • In contrast to traditional "top-down" genetic approaches that look for mutated versions of existing organisms.
  • Ex:Re-factoring and re-writing genomes from scratch.
  • Create chemical systems with biological behaviors (e.g., self-replication).
• Application of engineering principles to biology.
  • Standardized parts that give predictable outcomes when put together in different combinations.
  • Instantiating algorithms and problems from physics and math into biology. (e.g., oscillators)
  • Ex: circuits, DNA computing, metabolic engineering
  • Rewriting biological sequences in ways that could not be achieved (quickly) by natural evolution

Synthetic Biology Workshops

• 2003 Cold Spring Harbor Laboratory Synthetic Biology Course

Synthetic Biology Conferences/Sessions

Looking over the schedules of recent conferences is an excellent way to find new topics of interest or finds labs that are involved in synthetic biology.

SBx.0 Conference Series

• Synthetic Biology 6.0 (2013) main page
• Synthetic Biology 5.0 (2011) schedule

ASM

• American Society for Microbiology General Meeting (2013) schedule session1 session2
• American Society for Microbiology General Meeting (2012) session

Keystone

• Keystone Conference: Precision Genome Engineering and Synthetic Biology schedule

ICBE—International Conference on Biomolecular Engineering

• 4th ICBE (2013) schedule

Read More

Special Synthetic Biology Edition in the August 2012 Current Opinion in Chemical Biology

References

1. ISBN:0879694785

2. Smith H and Welcox KW. A Restriction enzyme from Hemophilus influenzae ☆: I. Purification and general properties. 1970. pmid:5312500 http://www.sciencedirect.com/science/article/pii/002228367090149X

3. Jackson DA, Symons RH, and Berg P. Biochemical method for inserting new genetic information into DNA of Simian Virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proc Natl Acad Sci U S A. 1972 Oct;69(10):2904-9. DOI:10.1073/pnas.69.10.2904 |

   Biochemical method for inserting new genetic information into DNA of Simian Virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli.

4. Fiers, W et al. 1976. Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene.

   http://www.regensci.org/twiki/pub/IGEM2009/BrainStorming/ms2article.pdf

5. Matteucci MD and Caruthers MH. 1981. Synthesis of Deoxyoligonucleotides on a Polymer Support. http://pubs.acs.org/doi/abs/10.1021/ja00401a041?prevSearch=matteucci%252C%2Bcaruthers%252C%2B1981&searchHistoryKey=

6. Fraley, RT et al. (1983) Expression of bacterial genes in plant cells. Proc. NatL. Acad. Sci. USA 80: 4803–4807 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC384133/

7. Elowitz MB and Leibler S. A synthetic oscillatory network of transcriptional regulators. Nature. 2000 Jan 20;403(6767):335-8. DOI:10.1038/35002125 |
8. Cello J, Paul AV, and Wimmer E. Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template. Science. 2002 Aug 9;297(5583):1016-8. DOI:10.1126/science.1072266 |

9. Knight, T. Idempotent Vector Design for Standard Assembly of Biobricks. 2003.

   http://hdl.handle.net/1721.1/21168
   

10. Smith HO, Hutchison CA 3rd, Pfannkoch C, and Venter JC. Generating a synthetic genome by whole genome assembly: phiX174 bacteriophage from synthetic oligonucleotides. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15440-5. DOI:10.1073/pnas.2237126100 |

    Generating a synthetic genome by whole genome assembly: phiX174 bacteriophage from synthetic oligonucleotides.

11. Gregory et al. The DNA sequence and biological annotation of human chromosome 1. 2006.

    http://www.nature.com/nature/journal/v441/n7091/full/nature04727.html
    

12. Cai Y, Hartnett B, Gustafsson C, and Peccoud J. A syntactic model to design and verify synthetic genetic constructs derived from standard biological parts. Bioinformatics. 2007 Oct 15;23(20):2760-7. DOI:10.1093/bioinformatics/btm446 |
13. 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, and Smith HO. Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome. Science. 2008 Feb 29;319(5867):1215-20. DOI:10.1126/science.1151721 |
14. 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, and Venter JC. Creation of a bacterial cell controlled by a chemically synthesized genome. Science. 2010 Jul 2;329(5987):52-6. DOI:10.1126/science.1190719 |
15. Andrianantoandro E, Basu S, Karig DK, and Weiss R. Synthetic biology: new engineering rules for an emerging discipline. Mol Syst Biol. 2006;2:2006.0028. DOI:10.1038/msb4100073 |

    Synthetic biology: new engineering rules for an emerging discipline

16. Benner SA and Sismour AM. Synthetic biology. Nat Rev Genet. 2005 Jul;6(7):533-43. DOI:10.1038/nrg1637 |

    Synthetic biology