Enabling technology biomaterials evolution platform
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Enabling Technology : Biomaterials Evolution Platform. 9:05-9:35 4-Feb-2009 Wyss Institute for Biologically Inspired Engineering. Thanks to:. Feb 10. 8:30-9:00: Jim Collins - Anticipatory Medical Devices 9:05-9:35: George Church - Biomaterial Evolution

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Enabling Technology : Biomaterials Evolution Platform

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Enabling technology biomaterials evolution platform

Enabling Technology : Biomaterials Evolution Platform

9:05-9:35 4-Feb-2009 Wyss Institute for Biologically Inspired Engineering

Thanks to:


Feb 10

Feb 10

8:30-9:00: Jim Collins - Anticipatory Medical Devices

9:05-9:35: George Church - Biomaterial Evolution

9:40-10:10: Joanna Aizenberg - Adaptive Architectures

10:15-10:45: Don Ingber - Programmable Nanomaterials

10:50-11:20: Don Ingber Biomimetic Microsystems


Biomaterials evolution platform

Biomaterials Evolution Platform

  • DNA Synthesis, assembly & analysis on chips

    • - VDJ-ome (antibody libraries)

  • 3-D DNA structures: inorganic interfaces

  • In vitro systems: multi-enzyme resistance

  • Microbial systems: multi-virus resistance

    • - Metabolic engineering fuels & chemicals

  • Human cell systems: combinatorial regulation

    • - Organ self-assembly


Sequencing tracked moore s law 2x 2 yr until 2005 9 10 000x 4yr

Sequencing tracked Moore’s law 2X/2 yr until 2005-9 10,000x/4yr

$/bp

2005 $50M

2009 $5K

2009 goal of 2% for $200 (coding + regulatory)


Enabling technology biomaterials evolution platform

Open-architecture hardware, software, wetware

e.g.

1981

IBM

PC

$150K - 2 billion beads/run

Polonator

Rich Terry

Senior Engineer


Dna synthesis assembly analysis on chips

DNA Synthesis, assembly & analysis on chips

Digital micromirror

& inkjet

Nitrobenzyl linkers for selective

release of beads or cells


Biomaterials evolution platform1

Biomaterials Evolution Platform

  • DNA Synthesis, assembly & analysis on chips

    • - VDJ-ome (antibody libraries)

  • 3-D DNA structures: inorganic interfaces

  • In vitro systems: multi-enzyme resistance

  • Microbial systems: multi-virus resistance

    • - Metabolic engineering fuels & chemicals

  • Human cell systems: combinatorial regulation

    • - Organ self-assembly


Antibody tcr vdj regions

Antibody (& TCR) VDJ regions

VH*DH*NH*JH*Vkl*Jkl

46*23*N * 6 * 67* 5 = > 2M combinations , 750 bp, >1E10 cells

Roth DB et al Mol Cell Biol. 1989 9:3049 N (1-13): 14 22 13 15 10 4 5 4 2 2 3 2 1

Lefranc, The Immunoglobulin FactsBook; Janeway, Immunobiology 2001


Biomaterials evolution platform2

Biomaterials Evolution Platform

  • DNA Synthesis, assembly & analysis on chips

    • - VDJ-ome (antibody libraries)

  • 3-D DNA structures: inorganic interfaces

  • In vitro systems: multi-enzyme resistance

  • Microbial systems: multi-virus resistance

    • - Metabolic engineering fuels & chemicals

  • Human cell systems: combinatorial regulation

    • - Organ self-assembly


First practical application of dna nanostructures

First practical application of DNA nanostructures

Residual NMR dipolar couplings for

membrane proteins >15kDa

Douglas, et al. PNAS 2007

10


Selection of dnas enabling selection of cnt structures

Selection of DNAs enabling selection of CNT structures

Material properties change at the sub-nm scale

(& sensitive to defects)

Carbon Nanotubes Tensile strength: 62,000 MPa

vs CNT-rope 3600, silk 1000, steel 800

Thermal conduction: 6000 W/mK vs Cu 385

Electrical current density of 4000 MA/cm2, vs Cu 4

C60 fullerite Bulk Modulus: 491 GPa

vs diamond 442, steel 160

metalic vs. semiconducting


Biomaterials evolution platform3

Biomaterials Evolution Platform

  • DNA Synthesis, assembly & analysis on chips

    • - VDJ-ome (antibody libraries)

  • 3-D DNA structures: inorganic interfaces

  • In vitro systems: multi-enzyme resistance

  • Microbial systems: multi-virus resistance

    • - Metabolic engineering fuels & chemicals

  • Human cell systems: combinatorial regulation

    • - Organ self-assembly


Mirror world resistant to enzymes parasites predators

Mirror world :resistant to enzymes, parasites, predators

Approach#1: De novo Chemical synthesis (below)

#2: Redesigned peptidyl transferase + D-AA-tRNAs (next slide)

352 AA Synthetic Dpo4 Sulfolobus DNA polymerase IV

4 peptide bonds left to construct

D-aminoacids

L-nucleotides

(Mirror-biopolymers)

L-aminoacids

D-nucleotides

(current biosphere)

Duhee

Bang


Synthetic life high speed accuracy route to mirror proteins jewett

Synthetic LifeHigh speed & accuracy Route to mirror proteinsJewett

113 kbp DNA 151 genes

Pure translation:

Forster & Church

MSB ’05 GenomeRes.’06

Shimizu, Ueda ’01


Biomaterials evolution platform4

Biomaterials Evolution Platform

  • DNA Synthesis, assembly & analysis on chips

    • - VDJ-ome (antibody libraries)

  • 3-D DNA structures: inorganic interfaces

  • In vitro systems: multi-enzyme resistance

  • Microbial systems: multi-virus resistance

    • - Metabolic engineering fuels & chemicals

  • Human cell systems: combinatorial regulation

    • - Organ self-assembly


Genome engineering multiplex automation gema for multi viral resistance

Genome Engineering Multiplex Automation (GEMA) for multi-viral resistance


Enabling technology biomaterials evolution platform

Genome Engineering Multiplex Automation (GEMASS)in vivo homologous allele replacement (lagging SS mimics)

3 hr Cycle time. Application: 314 change for multivirus resistance


Improving process yield health safety

Improving process yield, health, safety:

What threatens all biological systems?

What do all viruses have in common? or lack?


New genetic code viral resistance novel amino acids no functional gmo dna exchange

New genetic code: viral-resistance, novel amino acidsno functional GMO DNA exchange

PEG-pAcPhe-hGH (Ambrx) high serum stability

314 TAG to TAA changes

4

Isaacs

Charalel

Church

Sun

Wang

Carr

Jacobson

Kong

Sterling

1

3

2


Biomaterials evolution platform5

Biomaterials Evolution Platform

  • DNA Synthesis, assembly & analysis on chips

    • - VDJ-ome (antibody libraries)

  • 3-D DNA structures: inorganic interfaces

  • In vitro systems: multi-enzyme resistance

  • Microbial systems: multi-virus resistance

    • - Metabolic engineering fuels & chemicals

  • Human cell systems: combinatorial regulation

    • - Organ self-assembly


Accelerated evolution for valuable metabolites biofuels

Accelerated evolution for valuable metabolites & biofuels


Biomaterials evolution platform6

Biomaterials Evolution Platform

  • DNA Synthesis, assembly & analysis on chips

    • - VDJ-ome (antibody libraries)

  • 3-D DNA structures: inorganic interfaces

  • In vitro systems: multi-enzyme resistance

  • Microbial systems: multi-virus resistance

    • - Metabolic engineering fuels & chemicals

  • Human cell systems: combinatorial regulation

    • - Organ self-assembly


Re programming adult human cells to multiple tissues with combinations of dnas

Hair or skin sample

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


Combinations of regulatory genes

Combinations of regulatory genes

Viral delivery: β-catenin, Dnmt3l, Dppa2,3,4,5, Ecat1, Eras, Fthl17, Grb21, Ecat8, Fbx15, Gdf3, hTERT, Klf4, Myc, Nanog, Oct4, Rex1, Sall4, Sox2, Sox15, Stat3, Tcl1, Utf1

Signals:Activin, BMP4, Estrogen, FGF, HGF, PDGF, Retinoate, Shh, TGF, VEGF.

Cartilage & bone

Skin-derived stem cells

Immature Brain

Respiratory epithelium


Biomaterials evolution platform7

Biomaterials Evolution Platform

  • DNA Synthesis, assembly & analysis on chips

    • - VDJ-ome (antibody libraries)

  • 3-D DNA structures: inorganic interfaces

  • In vitro systems: multi-enzyme resistance

  • Microbial systems: multi-virus resistance

    • - Metabolic engineering fuels & chemicals

  • Human cell systems: combinatorial regulation

    • - Organ self-assembly


Enabling technology biomaterials evolution platform

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Enabling technology biomaterials evolution platform

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