Stochastic Mechanisms of Information Flow in Phosphate Economy of Escherichia coli

In previous work, we have presented a computational model and experimental results that quantify the dynamic mechanisms of auto-regulation in E. coli in response to varying external phosphate levels. In a cycle of deterministic ODE simulations and experimental verification, our model predicts and explores phenotypes with various modifications at the genetic level that can optimise inorganic phosphate intake. Here, we extend our analysis with extensive stochastic simulations at a single-cell level so that noise due to small numbers of certain molecules, e.g., genetic material, can be better observed. For the simulations, we resort to a conservative extension of Gillespie’s stochastic simulation algorithm that can be used to quantify the information flow in the biochemical system. Besides the common time series analysis, we present a dynamic visualisation of the time evolution of the model mechanisms in the form of a video, which is of independent interest. We argue that our stochastic analysis of information flow provides insights for designing more stable synthetic applications that are not affected by noise.

[1]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[2]  Ozan Kahramanogullari,et al.  Quantifying Information Flow in Chemical Reaction Networks , 2017, AlCoB.

[3]  Ozan Kahramanogullari On Quantitative Comparison of Chemical Reaction Network Models , 2019, HCVS/PERR@ETAPS.

[4]  K. Hammer,et al.  The Sequence of Spacers between the Consensus Sequences Modulates the Strength of Prokaryotic Promoters , 1998, Applied and Environmental Microbiology.

[5]  P. R. Jensen,et al.  Artificial promoters for metabolic optimization. , 1998, Biotechnology and bioengineering.

[6]  A. Oudenaarden,et al.  Nature, Nurture, or Chance: Stochastic Gene Expression and Its Consequences , 2008, Cell.

[7]  S. Furini,et al.  Phenotypic Variability in Synthetic Biology Applications: Dealing with Noise in Microbial Gene Expression , 2016, Front. Microbiol..

[8]  Aindrila Mukhopadhyay,et al.  Integrating Input from Multiple Signals: The VirA/VirG Two‐Component System of Agrobacterium tumefaciens , 2004, Chembiochem : a European journal of chemical biology.

[9]  D. Gillespie Exact Stochastic Simulation of Coupled Chemical Reactions , 1977 .

[10]  Juan Nogales,et al.  Quantifying dynamic mechanisms of auto-regulation in Escherichia coli with synthetic promoter in response to varying external phosphate levels , 2019, Scientific Reports.

[11]  O. Igoshin,et al.  Bistable responses in bacterial genetic networks: designs and dynamical consequences. , 2011, Mathematical biosciences.

[12]  P. Swain,et al.  Stochastic Gene Expression in a Single Cell , 2002, Science.

[13]  Mark Goulian,et al.  High stimulus unmasks positive feedback in an autoregulated bacterial signaling circuit , 2008, Proceedings of the National Academy of Sciences.

[14]  S. Howitt,et al.  Characterization of PitA and PitB fromEscherichia coli , 2001, Journal of bacteriology.

[15]  X. Xie,et al.  Probing Gene Expression in Live Cells, One Protein Molecule at a Time , 2006, Science.

[16]  Uri Alon,et al.  Input–output robustness in simple bacterial signaling systems , 2007, Proceedings of the National Academy of Sciences.

[17]  A. Arkin,et al.  Stochastic mechanisms in gene expression. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Steven E. Lindow,et al.  Predictive and Interpretive Simulation of Green Fluorescent Protein Expression in Reporter Bacteria , 2001, Journal of bacteriology.

[19]  D. K. Hawley,et al.  Compilation and analysis of Escherichia coli promoter DNA sequences. , 1983, Nucleic acids research.

[20]  Ozan Kahramanogullari,et al.  Stochastic flux analysis of chemical reaction networks , 2013, BMC Systems Biology.