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 GFP GFP X 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.