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PHILIPPE CLUZEL

Non-Genetic Individuality and Noise in Gene Regulation

Keywords: Network-gene regulation-chemotaxis-stochastic-fluorescence correlation spectroscopy

We propose an experimental and theoretical study of the chemotactic network in individual cells of the bacterium Escherichia coli. We believe that this well-characterized network is an ideal system to explore a general understanding of more complicated biochemical networks. We would like to address the issue of the sensitivity of this network to variations in its biochemical parameters. More specifically, if genetically identical cells are grown in an identical environment, how similar will their biochemical characteristics be? Spudich and Koshland (Ref 4) demonstrated individuality of bacterial cells grown in homogeneous conditions by showing characteristic behavioral differences which persist over their bacterial lifespan. To elucidate the origin of this non-genetic individuality, we are planing quantitative measurements (Fluorescence Correlation Spectroscopy) on single cells (rather than over a population) to correlate the behavior of a single cell with the concentration of its network components. We hypothesize that these behavioral differences have their molecular origin in fluctuations of the genetic expression of certain network components; these fluctuations might come from stochasticity of the chemical reactions involved in gene regulation. Numerical simulations will describe the randomness in the gene regulation. Using a previous model from our laboratory (Ref 6) that explains many aspects of bacterial chemotaxis, we will theoretically analyze it to understand the influence of such randomness on cellular behavior. We will emphasize a tight comparison of numerical results with quantitative data from individual cells.

 
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