mit molecular machines (jacobson) group [email protected] building a fab for synthetic biology
TRANSCRIPT
MIT Molecular Machines (Jacobson) Group
Building a FAB for Synthetic Biology
http://www.thetech.org/exhibits/online/robotzoo/about/chameleon.html
Synthetic Biology
to Program Cells to BecomeFactories to Make…
Devices, Sensors, Pharmaceuticals, Renewable Chemicals & Fuels and Food
Using Synthetic Genes…
Tape Programming of the Mark I Computer
Ribosome
only 106 times smaller Like this
Cells as Chemical Factories 1,3 Propanediol
http://3rdpartylogistics.blogspot.com/2011/10/genetic-bacteria-genetic-modification.htmlhttp://www.latonkorea.com/Plant.htmlhttp://3rdpartylogistics.blogspot.com/2011/10/genetic-bacteria-genetic-modification.htmlhttp://www.latonkorea.com/Plant.html
MB Elowitz MB and S Leibler (2000) A synthetic oscillatory network of transcriptional regulators.Nature.403 :335 - 338.
http://echinacea.harvard.edu/research/image-gallery/
Cells as Computers and LogicRing Oscillators from Transcriptional-Translational Logic
Jeff Hasty - UCSD
http://elowitz.caltech.edu/
Bacterial Ring Oscillators
tetRP RBS
T T’lacIP R
BS
T T’P R
BS
T T’
luxRP RBS
T T’luxIP R
BS
T T’P R
BS
T T’
ori resbackbone plasmidcfpP RBS
T T’
BBa_C0040 BBa_C0012
BBa_C0061BBa_C0062
BBa_E0022
BBa_R0051 BBa_R0040 BBa_R0010
BBa_R0010BBa_R0051BBa_R0063
BBa_R0040
TRBS
T’BBa_B0030BBa_B0010BBa_B0012
BB suffix BB prefixBBa_B0001
cIBBa_C0051
aiiABBa_C0060
Silicon
http://www.national.com/company/pressroom/gallery/graphics/full_sized/06_rgb.jpg http://commons.wikimedia.org/wiki/File:InternalIntegratedCircuit2.JPG http://en.labs.wikimedia.org/wiki/File:64-bit_lookahead_carry_unit.svg
From Schematic Design To Fab
To Working ChipTo Product
2
34
1
The Tyranny of Numbers
http://www.chipsetc.com/the-transistor.html
http://www.webenweb.co.uk/museum/comps.htm
DNA SynthesisChemical Synthesis
(Open Loop Protection Group)Biological Synthesis
(Error Correcting Polymerase)
Error Rate: 1:102
Throughput: 300 S per Base Additionhttp://www.med.upenn.edu/naf/services/catalog99.pdf
Throughput Error Rate Product Differential: ~108
template dependant 5'-3' primer extension
5'-3' error-correcting exonuclease
3'-5' proofreading exonuclease
Error Rate: 1:106
Throughput: 10 mS per
Base AdditionBeese et al. (1993), Science, 260, 352-355. http://www.biochem.ucl.ac.uk/bsm/xtal/teach/repl/klenow.html
A. Gene pathway sequence. B. Corresponding array of overlapping oligonucleotides C. Error correcting assembly in to low error rate pathways. D. Expression in cells
BioFAB - From Bits to CellsA B
CD
~ 1M Oligos/Chip
Next Generation (Chip Based) DNA Synthesis
Chow, Brian Y., Christopher J. Emig, and Joseph M. Jacobson. "Photoelectrochemical synthesis of DNA microarrays." Proceedings of the National Academy of Sciences 106.36 (2009): 15219-15224.
http://www.technologyreview.com/biomedicine/20035/
http://learn.genetics.utah.edu/content/labs/microarray/analysis
Accurate multiplex gene synthesis from programmable DNA microchipsJingdong Tian, Hui Gong, Nijing Sheng, Xiaochuan Zhou, Erdogan Gulari, Xiaolian Gao and George ChurchNature 432, 1050-1054(23 December 2004)doi:10.1038/nature03151
~1000x Lower Oligonucleotide Cost
J. Jacobson – MIT CBA – 5.1.14
1M
10G1T
100T
Base
Pai
rs
100M
~ 20
0 M
bp
~ 25
0 M
bp
~ 1.
5 G
bp
~ 1.
6 G
bp
~ 3.
2 G
bp
159.
8 G
bp
~ 20
0 G
bp
1000
0000
000
G T
rans
isto
rs
97 M
bp
~1-1
3 M
b
Scale Factors in DNA Synthesis & Applications Next Generation (Chip Based) DNA Synthesis
12.2
Mbp
The Genetic CodeCurrently Powering 8.7 Million Species on Earth Organisms
Currently Running the
Standard Genetic Code
Organisms Running a Different Genetic Code
hydrophobichydrophilic
Acetohalobium arabaticumCandida albicans
Pterobranchia mitochondrial code