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Connecting Minimal Synthetic Biology with Millibiology

Connecting Minimal Synthetic Biology with Millibiology. 16-Oct-2008 DARPA Cambridge, MA. Classification of replication/reproduction How close to atomic inputs ? (e.g. autotrophs use CO2, N2, etc.) Non-translational, non-universal construction replication:

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Connecting Minimal Synthetic Biology with Millibiology

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  1. Connecting Minimal Synthetic Biology with Millibiology 16-Oct-2008 DARPA Cambridge, MA • Classification of replication/reproduction • How close to atomic inputs ? • (e.g. autotrophs use CO2, N2, etc.) • Non-translational, non-universal construction replication: • Schulman & Winfree. ECAL 2005. Self-Replication and Evolution of DNA • crystals • Sievers D, von Kiedrowski G.Nature. 1994 Self-replication of complementary • nucleotide-based oligomers.

  2. 3 Exponential technologies“law of accelerating returns” Computation & Communication tRNA urea B12 Synthetic chemistry telegraph Analytic tRNA Shendure et al. 2004 Nature Reviews of Genetics. Kurzweil 2002; Moore 1965 (24 month doubling til 2020)

  3. $500 per 15Mbp NextGen Synthesis: off chip 8K Xeotron Photo-Generated Acid 12K Combimatrix Electrolytic 120K Roche, Febit Photolabile 5'protection 244K Agilent Ink-jet standard reagents Application to shRNA & exon capture libraries Tian et al. 2004 Nature Elledge, Hannon, et al.

  4. Not minimal genomesHigh speed & accuracy • Mycoplasma 500 RNA & protein genes • Mitochondria 1500 genes • Mike Jewett E.coli in vitro151 genes • Ease of synthesis • More radical designs • Existing applications • -Roche Rapid Translation System (RTS) • -Ambion ActivePro In Vitro Translation Kit • -Novagen, Promega, Invitrogen, Qiagen • Stratagene, Paragon, Amersham

  5. Not minimal:High speed & accuracy requires a few extra genes(E.coli 20 min. doubling) Reconstituted ribosomes:Jewett & Church 113 kbp DNA 151 genes Pure translation: Forster & Church MSB ’05 GenomeRes.’06 Shimizu, Ueda ’01

  6. 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 Charalel Church Isaacs Sun Wang Carr Jacobson Kong Sterling 1 3 2

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