VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwan

1

NOISE PROPAGATION INGENE NETWORKSJuan M. Pedraza and Alexander van Oudenaarden

2

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

NOISE

Fluctuations in concentrations

Cyan fluorescent protein

3

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

SCHEMATIC DESIGN

Promoters

Fluorescent proteins

CascadeUpstream gene Downstream gene

4

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

QUANTIFY

Correlation

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

gene number Self-correlations(variation)

Cross-correlations

, ,

iii C

12C 13C 23C

5

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

Different manner

6

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

SOURCES OF NOISE

Intrinsic noise Transmitted intrinsic noise from upstream

genes Global noise

7

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

INTRINSIC NOISE

Low copy numbers of mRNAs

8

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

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

9

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

TRANSMITTED INTRINSIC NOISE

Susceptibility Logarithmic gain

(average expression of j changes when i is varied)

10

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

TRANSMITTED INTRINSIC NOISE

Susceptibility(Cont.) Example

11

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

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)

12

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

NONINTERACTING GENES

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

23C

13

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

RESULT

Adding ATC

14

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

RESULT

15

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

DISCUSSION

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

16

VC

Lab, D

ept. o

f Com

pute

r Scie

nce

, NTH

U, Ta

iwa

n

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)