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Mukund Thattai NCBS Bangalore genetic networks in theory and practice
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1M1M Ecoli: The best understood living organism
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1M1M Ecoli: Complex matter that can be engineered
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Network biology DNA mRNA protein geneRNAP
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Network biology DNA mRNA protein geneRNAP regulator
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A biological wish-list Alberts et al., 1994 Embryonic development requires complex regulation [ ]Amplification [ ]Noise reduction [ ]Memory [ ]Oscillations
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Regulated genes ActivationInhibition X (D) [ ]Amplification [ ]Noise reduction [ ]Memory [ ]Oscillations
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Negative feedback [ ]Amplification [ ]Noise reduction [ ]Memory [ ]Oscillations
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Positive feedback [ ]Amplification [ ]Noise reduction [ ]Memory [ ]Oscillations
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Flip flop [ ]Amplification [ ]Noise reduction [ ]Memory [ ]Oscillations
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Hysteretic oscillator [ ]Amplification [ ]Noise reduction [ ]Memory [ ]Oscillations
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Ring oscillator [ ]Amplification [ ]Noise reduction [ ]Memory [ ]Oscillations
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Emergent network properties Amplification These predictions have been verified experimentally in engineered genetic networks Noise reductionMemoryOscillations
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Engineering Synthetic Networks parts.mit.edu Transcriptional regulators: DNA-binding proteins Reporters: Fluorescent proteins Inducers: Off-the-shelf chemicals The host strain: Escherichia coli Promoters: DNA segments that control gene expression
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Engineering Synthetic Networks parts.mit.edu The unity of biology allows us to combine modules in new and powerful ways
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Negative feedback Becskei & Serrano, 2000 P L tetO1tetR*-egfp P L tetO1tetR*-egfp X Noise reduction Figures adapted from Hasty et al, 2002
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Positive feedback Ozbudak & Thattai et al., 2004 P lac lacY P lac gfp TMG Memory
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Flip flop Gardner et al., 2000 P L s1con lacI Ptrc-2 cItsgfp IPTG Heat Memory Figures adapted from Hasty et al, 2002
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Ring oscillator Elowitz & Leibler, 2000 P L tetO1 cI P lac tetR PRPR lacI P L tetO1 gfp Oscillations Figures adapted from Hasty et al, 2002
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Getting your hands dirty...
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Elena Budrene New York Times
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