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genetic networks in theory and practice. Mukund Thattai NCBS Bangalore. Ecoli: The best understood living organism. 1 M. 1 M. Ecoli: Complex matter that can be engineered. Network biology. protein. mRNA. DNA. RNAP. gene. Network biology. protein. mRNA. regulator. DNA. RNAP.
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genetic networks in theory and practice Mukund Thattai NCBS Bangalore
1M Ecoli: Complex matter that can be engineered
Network biology protein mRNA DNA RNAP gene
Network biology protein mRNA regulator DNA RNAP gene
A biological wish-list Embryonic development requires complex regulation [] Amplification [ ] Noise reduction [ ] Memory [ ] Oscillations Alberts et al., 1994
Regulated genes Activation Inhibition (D) X [] Amplification [ ] Noise reduction [ ] Memory [ ] Oscillations
Negative feedback [] Amplification [] Noise reduction [ ] Memory [ ] Oscillations
Positive feedback [] Amplification [ ] Noise reduction [] Memory [ ] Oscillations
Flip flop [] Amplification [ ] Noise reduction [] Memory [ ] Oscillations
Hysteretic oscillator [] Amplification [ ] Noise reduction [ ] Memory [] Oscillations
Ring oscillator [] Amplification [ ] Noise reduction [ ] Memory [] Oscillations
Emergent network properties Amplification Noise reduction Memory Oscillations These predictions have been verified experimentally in engineered genetic networks
Engineering Synthetic Networks Inducers: Off-the-shelf chemicals Reporters: Fluorescent proteins Transcriptional regulators: DNA-binding proteins The host strain: Escherichia coli Promoters: DNA segments that control gene expression parts.mit.edu
Engineering Synthetic Networks The unity of biology allows us to combine modules in new and powerful ways parts.mit.edu
Negative feedback Noise reduction X PLtetO1 tetR*-egfp PLtetO1 tetR*-egfp Becskei & Serrano, 2000 Figures adapted from Hasty et al, 2002
Positive feedback Memory TMG Plac lacY Plac gfp Ozbudak & Thattai et al., 2004
Flip flop Memory IPTG PLs1con cIts gfp Ptrc-2 lacI Heat Gardner et al., 2000 Figures adapted from Hasty et al, 2002
Ring oscillator Oscillations PLtetO1 gfp PLtetO1 cI Plac lacI tetR PR Elowitz & Leibler, 2000 Figures adapted from Hasty et al, 2002
Elena Budrene New York Times