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Biomaterials Evolution

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

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Biomaterials Evolution

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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 Reprogramming • DNA as a Cost Effective Biomaterial

  2. Biomaterials Evolution Platform • DNA 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) 2

  3. 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)

  4. Open-architecture hardware, software, wetware e.g. 1981 IBM PC $150K - 2 billion beads/run Polonator Rich Terry Senior Engineer

  5. DNA Synthesis, assembly & analysis on chips Digital micromirror & inkjet Nitrobenzyl linkers for selective release of beads or cells

  6. Biomaterials Evolution Platform • DNA 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) 6

  7. Antibody (& TCR) VDJ regions VH*DH*NH*JH*Vkl*Jkl 46*23*N * 6 * 67* 5 = > 2M combinations , 750 bp, >1E10 cells 7

  8. Antibody- antigen pair selectionRibosome-display for biomimetic-microsystems antigens Antigen mRNA VDJ mRNA

  9. Biomaterials Evolution Platform • DNA 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) 9

  10. Hair or skin sample Re-programming adult human cells to multiple tissues with combinations of DNAs

  11. 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

  12. Biomaterials Evolution Platform • DNA 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) 12

  13. For metabolic optimization of fuels, biochemicals, pharmaceuticals Genome Engineering Multiplex Automation (GEMA) instrument

  14. Accelerated evolution for valuable metabolites & biofuels

  15. WIBIE Silver Lab Efforts Designer proteins for assembly into nanostructures (with Ingber) Engineered cellular memory and logic (with Collins/Ingber) Silver Lab Multi-Gene Switches for Cell Reprogramming DNA as a Cost- Effective Biomaterial Engineered electron transfer for bio-energy In silico design of “DeImmunized” antibody libraries (with Church) Directed Evolution of Human Antibodies Adaptive architecture/ nanomaterials Quantitatively designed protein therapeutics

  16. Poised for Industrial Collaborations 9:05-9:35 4-Feb-2009 Wyss Institute for Biologically Inspired Engineering Thanks to:

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