TY - JOUR T1 - Noise Contributions in an Inducible Genetic Switch: A Whole-Cell Simulation Study A1 - Roberts, Elijah A1 - Magis, Andrew A1 - Ortiz, Julio O. A1 - Baumeister, Wolfgang A1 - Luthey-Schulten, Zaida Y1 - 2011/03/10 N2 - Author Summary Expressing genes in a bacterial cell is noisy and random. A colony of bacteria grown from a single cell can show remarkable differences in the copy number per cell of a given protein after only a few generations. In this work we use computer simulations to study the variation in how individual cells in a population express a set of genes in response to an environmental signal. The modeled system is the lac genetic switch that Escherichia coli uses to find, collect, and process lactose sugar from the environment. The noise inherent in the genetic circuit controlling the cell's response determines how similar the cells are to each other and we study how the different components of the circuit affect this noise. Furthermore, an estimated 30–50% of the cell volume is taken up by a wide variety of large biomolecules. To study the response of the circuit caused by crowding, we simulate the circuit inside a three-dimensional model of an E. coli cell built using data from cryoelectron tomography reconstructions of a single cell and proteomics data. Correctly including random effects of molecular crowding will be critical to developing fully dynamic models of living cells. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 7 IS - 3 UR - https://doi.org/10.1371/journal.pcbi.1002010 SP - e1002010 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1002010 ER -