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1 Biomaterials Evolution This platform will create massively- parallel capabilities for directed evolution of biomolecules, such as DNA, for regenerative medicine and bioenergy Wyss 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
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Biomaterials Evolution

Dec 31, 2015

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Biomaterials Evolution. This platform will create massively-parallel capabilities for directed evolution of biomolecules, such as DNA, for regenerative medicine and bioenergy Wyss Faculty Lead: George Church Other Wyss Faculty: Pam Silver William Shih Jim Collins - PowerPoint PPT Presentation
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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

  • *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)

  • *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

  • *Open-architecture hardware, software, wetwarePolonator $150K - 2 billion beads/rune.g.1981IBM PCRich TerrySenior Engineer

  • *DNA Synthesis, assembly & analysis on chipsNitrobenzyl linkers for selective release of beads or cellsDigital micromirror & inkjet

  • *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)

  • *Antibody (& TCR) VDJ regionsVH*DH*NH*JH*Vkl*Jkl 46*23*N * 6 * 67* 5 = > 2M combinations , 750 bp, >1E10 cells

  • Antibody- antigen pair selectionRibosome-display for biomimetic-microsystems antigensAntigen mRNAVDJ mRNA

  • *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)

  • *Re-programming adult human cells to multiple tissues with combinations of DNAs

  • *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

  • *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)

  • Genome Engineering Multiplex Automation (GEMA) instrument

    For metabolic optimization of fuels, biochemicals, pharmaceuticals

  • *Accelerated evolution for valuable metabolites & biofuels

  • 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

  • *9:05-9:35 4-Feb-2009 Wyss Institute for Biologically Inspired EngineeringThanks to: Poised for Industrial Collaborations

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