Laboratoire Matière et Systèmes Complexes

Since the last decade, the relatively small copy number of proteins per cell has been recognized as a source of noise impacting most of cellular activities [1]. In particuliar, it has been shown that local noise transmits through genetic regulatory networks [2] but also that global noise affects all cellular components in a coordinated way [3]. In particular, activities such as metabolism and growth are extremely central to survival and fitness, though nothing is known about how they are affected by enzyme concentration fluctuations. We design a model system of the lac operon that allows us to probe the effect of the flucutations of a metabolic enzyme on growth rate in different cellular states. We follow exponentially growing colonies of E. Coli by time-lapse microscopy and obtain precise measurements of enzyme concentration and growth rate fluctuations at the level of single lineages. We analyze such data by looking at statistical correlations between the different signals. However, one has to note that growth rate and enzyme noise both potentially transmit to all other activities. To disentangle their effects, we make use of time delays and interpret the data at the light of a minimal but integrated model of the cell. We thus identify two important parameters describing the different possible and observed regimes : a dynamic control coefficient of the enzyme on growth rate, and the balance between volume and mass production. [1] Stochastic Gene Expression in a Single Cell, Elowitz MB, Levine AJ, Siggia ED, Swain PS, Science 297, 5584 (2002) [2] Noise propagation in gene networks,J. M. Pedraza and A. van Oudenaarden,Science 307, 1965 (2005). [3] Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells, Taniguchi, Yuichi Choi, Paul J. Li, Gene-Wei Chen, Huiyi Babu, Mohan Hearn, Jeremy Emili, Andrew Xie, X. Sunney, Science 239, 5991 (2010)