n oise p ropagation in g ene n etworks juan m. pedraza and alexander van oudenaarden 1 vc lab, dept....

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NOISE PROPAGATION INGENE NETWORKSJuan M. Pedraza and Alexander van Oudenaarden

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NOISE

Fluctuations in concentrations

Cyan fluorescent protein

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SCHEMATIC DESIGN

Promoters

Fluorescent proteins

CascadeUpstream gene Downstream gene

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QUANTIFY

Correlation

F: fluorescence levels i, j: indices refer to the

gene number Self-correlations(variation)

Cross-correlations

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iii C

12C 13C 23C

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Different manner

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SOURCES OF NOISE

Intrinsic noise Transmitted intrinsic noise from upstream

genes Global noise

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INTRINSIC NOISE

Low copy numbers of mRNAs

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TRANSMITTED INTRINSIC NOISE

Three factors Intrinsic noise for upstream gene The effect of temporal averaging(depends on the

lifetimes of the proteins) Susceptibility of the downstream gene to the

upstream one

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TRANSMITTED INTRINSIC NOISE

Susceptibility Logarithmic gain

(average expression of j changes when i is varied)

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TRANSMITTED INTRINSIC NOISE

Susceptibility(Cont.) Example

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GLOBAL NOISE

Cellular components change the reaction rate

Transmitted global fluctuation does not simply add to the direct global noise(because they are from same source)

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NONINTERACTING GENES

dominated by the global noisewhich is transmitted form gene 1to gene 2

23C

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RESULT

Adding ATC

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RESULT

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DISCUSSION

Noise-tolerant synthetic circuits in silico v.s. in vivo

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REFERENCE

Tom Ellis, Xiao Wang & James J Collins, Diversity-based, model-guided construction of synthetic gene networks with predicted functions, Nature Biotechnology 27, 465-471(2009)