Mukund ThattaiNCBS Bangalore

genetic networksin theory and practice

1M

Ecoli: The best understood living organism

1M

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

Activation Inhibition

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 reduction

Mem

ory

Oscillations

Engineering Synthetic Networks

parts.mit.edu

Transcriptional regulators:

DNA-binding proteins

Reporters:

Fluorescent proteins

Inducers:

Off-the-shelf chemicals

The host strain:

Escherichia coliPromoters:

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

PLtetO1 tetR*-egfp

PLtetO1 tetR*-egfp

X

Noise reduction

Figures adapted from Hasty et al, 2002

Positive feedback

Ozbudak & Thattai et al., 2004

Plac lacY

Plac gfp

TMG

Memory

Flip flop

Gardner et al., 2000

PLs1con

lacI Ptrc-2

cIts gfpIPTG

Heat

Memory

Figures adapted from Hasty et al, 2002

Ring oscillator

Elowitz & Leibler, 2000

PLtetO1

cI

Plac

tetR PR

lacI

PLtetO1

gfp

Oscillations

Figures adapted from Hasty et al, 2002

Getting your hands dirty...

Elena Budrene

New York Times