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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
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)

slide5
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
slide17
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
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
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
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