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The discovery of fluorescent proteins and the use of fluorescently labeled antisense primers for in situ hybridization of mRNA molecules ("FISH"), have made it possible to observe gene expression at the level of single gene molecules. Such analyses have revealed that gene product molecule numbers fluctuate in time and across populations of identical cells. This discovery provides new opportunities and challenges for biologists.

What are the origins of this gene expression "noise", and how can statistical behavior at the molecular level be reconciled with the apparently high degree of determinism that biological functions demand?

On the other hand, work that employs stochastic process theory to describe gene expression indicates that the analysis of gene expression fluctuations may be used to address previously intractable questions regarding the mechanism of transcriptional regulation.

We largely focus on extending such efforts to the analysis of chromatin structure fluctuations, and their inclusion into stochastic gene expression models. To this end, we have developed experimental techniques that now allow us to investigate the nucleosome configuration of single gene molecules by electron microscopy. This approach is combined with molecular genetics, fluorescence microscopy, and mathematical modeling.