RT Journal Article SR Electronic T1 Generation and attenuation of variability in a bacterial signaling network revealed by single-cell FRET JF bioRxiv FD Cold Spring Harbor Laboratory SP 124008 DO 10.1101/124008 A1 J.M. Keegstra A1 K. Kamino A1 F. Anquez A1 M.D. Lazova A1 T. Emonet A1 T.S. Shimizu YR 2017 UL http://biorxiv.org/content/early/2017/04/14/124008.abstract AB We present in vivo single-cell FRET measurements in the Escherichia coli chemotaxis system that reveal pervasive signaling variability, both across cells in isogenic populations and within individual cells over time. We quantify cell-to-cell variability of adaptation, ligand response, as well as steady-state output level, and analyze the role of network design in shaping this diversity from gene expression noise. In the absence of changes in gene expression, we find that single cells demonstrate strong temporal fluctuations. We provide evidence that such signaling noise can arise from at least two sources: (i) stochastic activities of adaptation enzymes, and (ii) receptor-kinase dynamics in the absence of adaptation. We demonstrate that under certain conditions, (ii) can generate giant fluctuations that drive signaling activity of the entire cell into a stochastic two-state switching regime. Our findings underscore the importance of molecular noise, arising not only in gene expression but also in protein networks.