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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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Mukund Thattai NCBS Bangalore

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Mukund thattai ncbs bangalore

genetic networks

in theory and practice

Mukund Thattai

NCBS Bangalore


Mukund thattai ncbs bangalore

Ecoli: The best understood living organism

1M


Mukund thattai ncbs bangalore

1M

Ecoli: Complex matter that can be engineered


Mukund thattai ncbs bangalore

Network biology

protein

mRNA

DNA

RNAP

gene


Mukund thattai ncbs bangalore

Network biology

protein

mRNA

regulator

DNA

RNAP

gene


Mukund thattai ncbs bangalore

A biological wish-list

Embryonic development requires complex regulation

[]Amplification

[ ]Noise reduction

[ ]Memory

[ ]Oscillations

 Alberts et al., 1994


Mukund thattai ncbs bangalore

Regulated genes

Activation

Inhibition

(D)

X

[]Amplification

[ ]Noise reduction

[ ]Memory

[ ]Oscillations


Mukund thattai ncbs bangalore

Negative feedback

[]Amplification

[]Noise reduction

[ ]Memory

[ ]Oscillations


Mukund thattai ncbs bangalore

Positive feedback

[]Amplification

[ ]Noise reduction

[]Memory

[ ]Oscillations


Mukund thattai ncbs bangalore

Flip flop

[]Amplification

[ ]Noise reduction

[]Memory

[ ]Oscillations


Mukund thattai ncbs bangalore

Hysteretic oscillator

[]Amplification

[ ]Noise reduction

[ ]Memory

[]Oscillations


Mukund thattai ncbs bangalore

Ring oscillator

[]Amplification

[ ]Noise reduction

[ ]Memory

[]Oscillations


Mukund thattai ncbs bangalore

Emergent network properties

Amplification

Noise reduction

Memory

Oscillations

These predictions have been verified experimentally in engineered genetic networks


Mukund thattai ncbs bangalore

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


Mukund thattai ncbs bangalore

Engineering Synthetic Networks

The unity of biology allows us to combine modules in new and powerful ways

 parts.mit.edu


Mukund thattai ncbs bangalore

Negative feedback

Noise reduction

X

PLtetO1

tetR*-egfp

PLtetO1

tetR*-egfp

 Becskei & Serrano, 2000

 Figures adapted from Hasty et al, 2002


Mukund thattai ncbs bangalore

Positive feedback

Memory

TMG

Plac

lacY

Plac

gfp

 Ozbudak & Thattai et al., 2004


Mukund thattai ncbs bangalore

Flip flop

Memory

IPTG

PLs1con

cIts

gfp

Ptrc-2

lacI

Heat

 Gardner et al., 2000

 Figures adapted from Hasty et al, 2002


Mukund thattai ncbs bangalore

Ring oscillator

Oscillations

PLtetO1

gfp

PLtetO1

cI

Plac

lacI

tetR

PR

 Elowitz & Leibler, 2000

 Figures adapted from Hasty et al, 2002


Mukund thattai ncbs bangalore

Getting your hands dirty...


Mukund thattai ncbs bangalore

Elena Budrene

New York Times


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