Download Slide 1

Noise in cellular circuitry
-Noise may be essential for many cellular processes
-Phenotypic variations in populations of cell is conjectured to be related to noise
(fluctuation) in gene expression.
-How do we quantify noise, and how do we identify the mechanisms by which it is
generated?
Elowitz, MB, Levine, AJ, Siggia, ED, and Swain, PS.
Stochastic gene expression in a single cell. Science (2002), 297:1183-1186.
Quantifying gene expression: using GFP
Use a reporter gene whose product can be quantified: Green Fluorescence Protein
DNA
GFP
Quantifying gene expression: effects of the environment
A) In the presence of the repressor LacI:
Glucose
X
X*
LacI
No transcription
X*
DNA
GFP
B) When the repressor LacI is inhibited
X
GFP
GFP
X*
Lactose or IPTG
transcription
GFP
Two mechanisms for noise in gene expression
Intrinsic noise: inherent noise in the expression of the gene that comes from random
events that govern the chemical reactions related to the process; hint
Extrinsic noise: Fluctuations in the amounts of other cellular components that affect
gene expression (concentrations, states and locations of molecules
such as transcription factors and/or polymerases); hext
The total noise htot is the combination of these two mechanisms. It can be shown that:
hext2+hint2=htot2
(Swain, PS, Elowitz, MB, and Siggia, ED. Intrinsic and extrinsic contributions to stochasticity
in gene expression. Proc. Natl. Acad. Sci. (USA), 99, 12795-12800 (2002).
Intrinsic and extrinsic noise can be measured
and distinguished with 2 genes
A: in the absence of intrinsic noise, expression of the two genes are correlated;
cells have the same color
B. In the presence of intrinsic noise, gene expression becomes uncorrelated; changes in color
The construction to quantify noise
YFP
Quantifying noise
With c(i) and y(i) the average CFP and YFP intensity of the i-th cell, respectively, and <>
denotes means over the cell population.