Synthetic Biology A Brief Survey http newsmitedu topicsyntheticbiology What is Synthetic Biology Synthetic biology is programming biological matter Schwille P Science 333 12524 2011 ID: 791010
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Slide1
1
Isaac Larkin 01/11/2016
Synthetic Biology:
A Brief Survey
http://
news.mit.edu
/topic/synthetic-biology
Slide2What is Synthetic Biology?
Synthetic biology is programming biological matter.
Schwille, P. Science 333, 1252–4 (2011).
Slide3The Synthetic Biology Stack
DNA Sequencing and Synthesis
DNA AssemblyDNA Insertion/Genome ManipulationBiomolecule “Part” Characterization and DesignBiomolecular Circuit/“Device” Characterization and Design
Level of
Abstraction
Slide4Falling Cost of DNA Sequencing and Synthesis Facilitates Synthetic Biology
synthesis.cc
/2014/02/time-for-new-cost-curves-2014.htmlIDT oligo synthesis (iBuy):15-60 bp for $0.01-$0.03 /base/nmole
Slide5Falling Cost of DNA Sequencing and Synthesis Facilitates Synthetic Biology
Elizabeth
Segran, Fast Company, 2015 (goo.gl/l4JGnP)http://www.incubizz.de/index.php/twist-bioscienceTwist’s Price: 10¢ / base
Slide6Advances in DNA Assembly Enable Whole Genome Synthesis
Holt, R. A.Nat. Biotechnol. 26, 296–7 (2008).
Assembly strategy for synthetic genomes
Slide7Advances in DNA Assembly Enable Whole Genome Synthesis
neb.com
/products/synbio.tsl.ac.uk/gibson-assembly/Gibson AssemblyUp to 10fragmentsat onceOne pot,50ºC,15-60 min
Slide8Advances in DNA Assembly Enable Whole Genome Synthesis
j
cvi.org, 2010Mycoplasma laboratorium
Slide9Advances in DNA Assembly Enable Whole Genome Synthesis
s
yntheticyeast.orgSynthetic Yeast Project
Slide10Advances in DNA Assembly Enable Whole Genome Synthesis
Science 344, 55–8 (2014).
Synthetic Yeast Project
Slide11Genome Manipulation Leads to Rewriting the Genetic Code
Wang, H. H. et al. Nature 460, 894–8 (2009).
MAGE enables rapid, introduction of ~10 simultaneous mutations in E. coliMAGE:Multiplex AutomatedGenome Engineeringin E. coli
Slide12Genome Manipulation Leads to Rewriting the Genetic Code
Ma, N. J., Moonan, D. W. &
Isaacs, F. J. Nat. Protoc. 9, 2285–300 (2014)Only 314 UAGin the wholeE. coli genome!
Slide13Genome Manipulation Leads to Rewriting the Genetic Code
Ma, N. J., Moonan, D. W. &
Isaacs, F. J. Nat. Protoc. 9, 2285–300 (2014)CAGE enables genome-wide UAGUAA codon reassignment(Science 2013)
Slide14Genome Manipulation Leads to Rewriting the Genetic Code
Lajoie, M. J. et al. Science 342, 357–60 (2013
)Genomically Recoded Organisms (GROs) enable efficient NSAA incorporation
Slide15Genome Manipulation Leads to Rewriting the Genetic Code
Azides
Alkynes
Fluorophores
Photo-
Crosslinker
Quast
, R. B. et al. FEBS Lett. 589, 1703–12 (2015)
Slide16Prediction and Programming of Biomolecule Structure is Improving
Predicted Structure
Crystal StructureMarks, D. S., Hopf, T. A. & Sander, C. Nat. Biotechnol. 30, 1072–80 (2012)
Slide17Prediction and Programming of Biomolecule Structure is Improving
King, N. P. et al. Nature 510, 103–8 (2014
)Baker Lab designs 2-component, tetrahedral protein nanoparticles
Slide18Prediction and Programming of Protein Structure is Improving
King, N. P. et al. Nature 510, 103–8 (2014
)Baker Lab designs 2-component, tetrahedral protein nanoparticles
Slide19Design of Biomolecule Function Produces Novel “Parts” for Synthetic Biologists
http://2011.igem.org/Team:DTU-Denmark
/Project_improving_araBADDNA promoter libraries enable tuning of maximum expression
Slide20Design of Biomolecule Function Produces Novel “Parts” for Synthetic Biologists
Spinach:
An RNA mimic of GFPPaige, J. S., Wu, K. Y. & Jaffrey, S. R. Science 333, 642–6 (2011).
Slide21Design of Biomolecule Function Produces Novel “Parts” for Synthetic Biologists
Paige
, J. S., Wu, K. Y. & Jaffrey, S. R. Science 333, 642–6 (2011).
Slide22Design of Biomolecule Function Produces Novel “Parts” for Synthetic Biologists
Enzyme engineering: still really hard, but not impossible
Engineered formolase (FLS): -Incorporates formaldehyde into central metabolism-Potentially, a new CO2 fixation routeSiegel, J. B. et al. Proc. Natl. Acad. Sci. 112, 3704–9 (2015).
Slide23From Parts to Complex Devices: Design of Genetic Circuits
1. Cameron, D. E.,
Bashor, C. J. & Collins, J. J. Nat. Rev. Microbiol. 12, 381–90 (2014).Origin of the field!
Slide24From Parts to Complex Devices: Design of Genetic Circuits
1. Cameron, D. E.,
Bashor, C. J. & Collins, J. J. Nat. Rev. Microbiol. 12, 381–90 (2014).Origin of the field!
Slide25From Parts to Complex Devices: Design of Genetic Circuits
1.
Elowitz, M. B. & Leibler, S. Nature 403, 335–8 (2000).Circuit fidelity has improved
Slide26From Parts to Complex Devices: Design of Genetic Circuits
1. Danino, T. et al.
Nature 463, 326–30 (2010).Circuit fidelity has improved
Slide27Therapeutic Genetic Circuits
Cellular system to sense and repress psoriasis in mice
1. Schukur, L. et al. Sci. Transl. Med. 7, 318ra201–318ra201 (2015).
Slide28Programming Metabolic Circuits to Make Useful Small Molecules
1
st triumph:Artemisinic AcidProductionPaddon, C. J. et al. Nature 496, 528–32 (2013).
Slide29Programming Metabolic Circuits to Make Useful Small Molecules
1
st triumph:Artemisinic AcidProductionPaddon, C. J. et al. Nature 496, 528–32 (2013).At an economically viable scale! (After 7 years of optimizing).~700-fold betterthan first strain’s yield!
Slide30Programming Metabolic Circuits to Make Useful Small Molecules
Complete Opiate
Biosynthesis in Yeast(Currently tinyyields)1. Galanie, S. et al. Science (80-. ). 349, 1095–1100 (2015).
Slide31The Synthetic Biology Stack
DNA Sequencing and Synthesis
DNA AssemblyDNA Insertion/Genome ManipulationBiomolecule “Part” Characterization and DesignBiomolecular Circuit/“Device” Characterization and Design
Level of
Abstraction
Slide32Thanks!
1. http://
www.tsienlab.ucsd.edu/HTML/Images/IMAGE%20-%20PLATE%20-%20Beach.jpgSarahJoeWestonMike JewettThe NU Synthetic Biology Center