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:

2. Quantifying gene expression: using GFP
Use a reporter gene whose product can be quantified: Green Fluorescence Protein
DNA
GFP

3. 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
GFP
GFP X X*
Lactose or IPTG
transcription
GFP

4. 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, (2002).

5. 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

6. The construction to quantify noise
YFP

7. 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.