Mukund Thattai NCBS Bangalore genetic networks in theory and practice

1M1M Ecoli: The best understood living organism

1M1M Ecoli: Complex matter that can be engineered

Network biology DNA mRNA protein geneRNAP

Network biology DNA mRNA protein geneRNAP regulator

A biological wish-list  Alberts et al., 1994 Embryonic development requires complex regulation [ ]Amplification [ ]Noise reduction [ ]Memory [ ]Oscillations

Regulated genes ActivationInhibition X  (D) [  ]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 These predictions have been verified experimentally in engineered genetic networks Noise reductionMemoryOscillations

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

Engineering Synthetic Networks  parts.mit.edu The unity of biology allows us to combine modules in new and powerful ways

Negative feedback  Becskei & Serrano, 2000 P L tetO1tetR*-egfp P L tetO1tetR*-egfp X Noise reduction  Figures adapted from Hasty et al, 2002

Positive feedback  Ozbudak & Thattai et al., 2004 P lac lacY P lac gfp TMG Memory

Flip flop  Gardner et al., 2000 P L s1con lacI Ptrc-2 cItsgfp IPTG Heat Memory  Figures adapted from Hasty et al, 2002

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

Getting your hands dirty...

Elena Budrene New York Times