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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)


Open-architecture hardware, software, wetware 10,000x/4yr

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 10,000x/4yr

Digital micromirror

& inkjet

Nitrobenzyl linkers for selective

release of beads or cells


Biomaterials evolution platform1
Biomaterials Evolution Platform 10,000x/4yr

  • 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 10,000x/4yr(& 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 10,000x/4yr

  • 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 10,000x/4yr

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 10,000x/4yr

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 10,000x/4yr

  • 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 : 10,000x/4yrresistant 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 Life 10,000x/4yrHigh 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 10,000x/4yr

  • 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) 10,000x/4yrfor multi-viral resistance


Genome Engineering Multiplex Automation (GEMASS) 10,000x/4yrin 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: 10,000x/4yr

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: 10,000x/4yr 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 10,000x/4yr

  • 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 10,000x/4yr

  • 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 10,000x/4yr

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


Combinations of regulatory genes
Combinations of regulatory genes 10,000x/4yr

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 10,000x/4yr

  • 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


. 10,000x/4yr


. 10,000x/4yr


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