Biomaterials Evolution
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*Biomaterials EvolutionThis platform will create massively-parallel capabilities for directed evolution of biomolecules, such as DNA, for regenerative medicine and bioenergyWyss Faculty Lead: George Church
Other Wyss Faculty: Pam Silver William Shih Jim Collins Don Ingber
Overall Goals: Directed Evolution of Human Antibodies Multi-Gene Switches for Cell Reprogramming DNA as a Cost Effective Biomaterial
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*Biomaterials Evolution PlatformDNA Synthesis, assembly & analysis on chips -DNA as a Cost Effective Biomaterial (Shih) -Human Antibody & Antigen Libraries (Ingber)Directed Evolution of Microbial Communities -Metabolic engineering fuels, chemicals (Silver, Collins)Gene Switches for Human Cell Reprogramming -Combinatorial Control of Stem Cell & Cancer Cell Differentiation (Ingber & Collins)
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*Sequencing tracked Moores law 2X/2 yr until 2005-9 10,000x/4yr2009 goal of 2% for $200 (coding + regulatory)$/bp2005 $50M2009 $5K
Chart1
10
1
0.99
0.5
0.09
0.07
0.05
0.03
0.0036666667
0.0001666667
0.0000166667
0.0000008333
CF2
companycostgenome sizethroughputread lengthcoveragetimedaysdate of sourcecost/bpcost/kB (gene)reduction/yrsource
$bpmb/daywkdollars0.01$ (cents)/1000 bp
sanger6.0E+91990101000000CREDIT: ADAPTED FROM GRAPH PROVIDED BY JEFFREY SCHLOSS/NHGRI, http://images.google.com/imgres?imgurl=http://singularity.com/images/charts/DNAsequencingCost.jpg&imgrefurl=http://singularity.com/charts/page73.html&h=1168&w=1523&sz=140&hl=en&start=4&sig2=xWb
sanger6.0E+9199511000002.00
sanger6.0E+919960.99990001.01
HGP (sanger)3.0E+96.0E+92800676473219970.5500001.98http://www.bloomberg.com/apps/news?pid=20601087&sid=aAgJB2R0Wcqs&refer=home, http://www.sciencemag.org.www.library.gatech.edu:2048/cgi/content/full/311/5767/1544#table
sanger6.0E+920010.0990001.39
sanger6.0E+920020.0770001.29
sanger6.0E+920030.0550001.40
sanger6.0E+920040.0330001.67
optimized sanger sequencing2.2E+76.0E+920053.7E-3366.678.2http://www.sciencemag.org.www.library.gatech.edu:2048/cgi/content/full/311/5767/1544#table
4541.0E+66.0E+99685620071.7E-416.6711.0http://www.sciencemag.org.www.library.gatech.edu:2048/cgi/content/full/311/5767/1544#table
Illumina1.0E+56.0E+95003642820081.7E-51.6710.0
CGI5.0E+36.0E+910004020098.3E-70.0820.0http://www.sciencemag.org.www.library.gatech.edu:2048/cgi/content/full/311/5767/1544#table
Danaher6.0E+9
Agencourt6.0E+9
ABI6.0E+9
LICOR6.0E+9
Microchip Biotechnologies6.0E+9
NimbleGen6.0E+9
6.0E+9
Archon X Prize1.0E+36.0E+90.010.100.02http://www.eyeondna.com/2008/02/11/whole-genome-sequencing-costs-continue-to-drop/
CF2
CF
costs to sequence genome
started oct 08
craig forest
companycostgenome sizethroughputread lengthcoveragetimedaysdate of sourcecost/bpcost/kB (gene)reduction/yrsource
$bpmb/daywkdollars0.01$ (cents)/1000 bp
sanger6.0E+91990101000000CREDIT: ADAPTED FROM GRAPH PROVIDED BY JEFFREY SCHLOSS/NHGRI, http://images.google.com/imgres?imgurl=http://singularity.com/images/charts/DNAsequencingCost.jpg&imgrefurl=http://singularity.com/charts/page73.html&h=1168&w=1523&sz=140&hl=en&start=4&sig2=xWb
sanger6.0E+9199511000002.00
sanger6.0E+919960.99990001.01
HGP (sanger)3.0E+96.0E+92800676473219970.5500001.98http://www.bloomberg.com/apps/news?pid=20601087&sid=aAgJB2R0Wcqs&refer=home, http://www.sciencemag.org.www.library.gatech.edu:2048/cgi/content/full/311/5767/1544#table
sanger6.0E+920010.0990001.39
sanger6.0E+920020.0770001.29
sanger6.0E+920030.0550001.40
sanger6.0E+920040.0330001.67
optimized sanger sequencing2.2E+76.0E+920053.7E-3366.678.2http://www.sciencemag.org.www.library.gatech.edu:2048/cgi/content/full/311/5767/1544#table
4541.0E+66.0E+99685620071.7E-416.6711.0http://www.sciencemag.org.www.library.gatech.edu:2048/cgi/content/full/311/5767/1544#table
Illumina1.0E+56.0E+95003642820081.7E-51.6710.0
CGI5.0E+36.0E+910004020098.3E-70.0820.0http://www.sciencemag.org.www.library.gatech.edu:2048/cgi/content/full/311/5767/1544#table
Danaher6.0E+9
Agencourt6.0E+9
ABI6.0E+9
LICOR6.0E+9
Microchip Biotechnologies6.0E+9
NimbleGen6.0E+9
6.0E+9
Archon X Prize1.0E+36.0E+90.010.100.02http://www.eyeondna.com/2008/02/11/whole-genome-sequencing-costs-continue-to-drop/
http://www.nature.com.www.library.gatech.edu:2048/nbt/journal/v25/n2/full/nbt0207-149.html
Human Genome Project Information, http://www.ornl.gov/sci/techresources/Human_Genome/project/privatesector.shtml;
Stanford Genome Technology Center, http://sequence-www.stanford.edu/group/techdev/auto.html;
National Human Genome Research Institute, http://www.genome.gov;
Tabitha Powledge, How Many Genomes Are Enough? Scientist, November 17, 2003, http://www.biomedcentral.com/news/20031117/07.
CF
Year
cost (cents)/gene (1000 bp)
GMC
YearDaltons synthBits/secSeq bp/$SynComm/Seq
1830urea-Wohler 1828
18406E+11E+0telegraph
19408E+11E+3
19501E+21E+5
19654E+21E+60.001tRNA-Holley (seq)
19721E+31E+70.003B12-Woodward(syn)
19733E+43.00E+070.01tRNA-Khorana (syn)
19801.00E+051E+80.04pBR322 (seq)
19903E+51E+100.4
19956E+51.00E+111H.pylori
19991E+61.00E+125
20025E+61E+1310polio (syn)human genome draft
20041E+71000operon HMS(syn)
20063E+73.00E+03operon Kosan (syn)
20073E+86.00E+05Mycoplasma (syn)
20083E+95.00E+06E.coli (chip syn)Polonator 10X-coverage
2009
GMC
183018301830
6011840
8010001940
1001000001950
40010000000.001
1355100000000.003
25080300000000.01
1000001000000000.04
300000100000000000.4
6000001000000000001
100000010000000000005
49500001000000000000010
1056000020041000
3300000020063000
3300000002007600000
330000000020085000000
Daltons synth
Bits/sec
Seq bp/$
GMC2
SynYearSyn b/$Seq b/$Seq
19801.67E-030.04pBR322 (seq)
19900.4
19951H.pylori
19995
polio (syn)20021human genome draft
operon HMS(syn)200420Celera
operon Kosan (syn)200660JCV
Mycoplasma (syn)20076.0E+5JDW
E.coli (chip syn)20083E+41.2E+6Polonator 10X-coverage
2009
GMC2
Syn b/$
Seq b/$
ApoE
20.130.0162/2
0.152/3
0.0172/4
30.740.553/3
0.253/4
40.130.0174/4
11.00
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*Open-architecture hardware, software, wetwarePolonator $150K - 2 billion beads/rune.g.1981IBM PCRich TerrySenior Engineer
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*DNA Synthesis, assembly & analysis on chipsNitrobenzyl linkers for selective release of beads or cellsDigital micromirror & inkjet
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*Biomaterials Evolution PlatformDNA Synthesis, assembly & analysis on chips -DNA as a Cost Effective Biomaterial (Shih) -Human Antibody & Antigen Libraries (Ingber)Directed Evolution of Microbial Communities -Metabolic engineering fuels, chemicals (Silver, Collins)Gene Switches for Human Cell Reprogramming -Combinatorial Control of Stem Cell & Cancer Cell Differentiation (Ingber & Collins)
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*Antibody (& TCR) VDJ regionsVH*DH*NH*JH*Vkl*Jkl 46*23*N * 6 * 67* 5 = > 2M combinations , 750 bp, >1E10 cells
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Antibody- antigen pair selectionRibosome-display for biomimetic-microsystems antigensAntigen mRNAVDJ mRNA
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*Biomaterials Evolution PlatformDNA Synthesis, assembly & analysis on chips -DNA as a Cost Effective Biomaterial (Shih) -Human Antibody & Antigen Libraries (Ingber)Directed Evolution of Microbial Communities -Metabolic engineering fuels, chemicals (Silver, Collins)Gene Switches for Human Cell Reprogramming -Combinatorial Control of Stem Cell & Cancer Cell Differentiation (Ingber & Collins)
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*Re-programming adult human cells to multiple tissues with combinations of DNAs
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*Viral delivery: -catenin, Dnmt3l, Dppa2,3,4,5, Ecat1, Eras, Fthl17, Grb21, Ecat8, Fbx15, Gdf3, hTERT, Klf4, Myc, Nanog, Oct4, Rex1, Sall4, Sox2, Sox15, Stat3, Tcl1, Utf1Signals: Activin, BMP4, Estrogen, FGF, HGF, PDGF, Retinoate, Shh, TGF, VEGF.Combinations of regulatory genesCartilage & boneRespiratory epitheliumImmature BrainSkin-derived stem cells
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*Biomaterials Evolution PlatformDNA Synthesis, assembly & analysis on chips -DNA as a Cost Effective Biomaterial (Shih) -Human Antibody & Antigen Libraries (Ingber)Directed Evolution of Microbial Communities -Metabolic engineering fuels, chemicals (Silver, Collins)Gene Switches for Human Cell Reprogramming -Combinatorial Control of Stem Cell & Cancer Cell Differentiation (Ingber & Collins)
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Genome Engineering Multiplex Automation (GEMA) instrument
For metabolic optimization of fuels, biochemicals, pharmaceuticals
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*Accelerated evolution for valuable metabolites & biofuels
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WIBIE Silver Lab EffortsSilver LabDNA as a Cost- Effective BiomaterialDirected Evolution of Human AntibodiesMulti-Gene Switches for Cell ReprogrammingDesigner proteins for assembly into nanostructures(with Ingber)In silico design of DeImmunized antibody libraries (with Church)Engineered cellular memory and logic(with Collins/Ingber)Quantitatively designed protein therapeuticsEngineered electron transfer for bio-energyAdaptive architecture/ nanomaterials
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*9:05-9:35 4-Feb-2009 Wyss Institute for Biologically Inspired EngineeringThanks to: Poised for Industrial Collaborations
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