TY - JOUR T1 - Detection of transcriptional triggers in the dynamics of microbial growth: application to the respiratory-versatile bacterium Shewanella oneidensis JF - Nucleic Acids Research, Volume 40, Issue 15, August 2012, Pages 7132-7149 Y1 - 2012 A1 - Q Beg A1 - Mattia Zampieri A1 - N Klitgord A1 - S Collins A1 - M Serres A1 - Daniel Segrè A1 - Claudio Altafini AB - The capacity of microorganisms to respond to variable external conditions requires a coordination of environment-sensing mechanisms and decisionmaking regulatory circuits. Here, we seek to understand the interplay between these two processes by combining high-throughput measurement of time-dependent mRNA profiles with a novel computational approach that searches for key genetic triggers of transcriptional changes. Our approach helped us understand the regulatory strategies of a respiratorily versatile bacterium with promising bioenergy and bioremediation applications, Shewanella oneidensis, in minimal and rich media. By comparing expression profiles across these two conditions, we unveiled components of the transcriptional program that depend mainly on the growth phase. Conversely, by integrating our time-dependent data with a previously available large compendium of static perturbation responses, we identified transcriptional changes that cannot be explained solely by internal network dynamics, but are rather triggered by specific genes acting as key mediators of an environment-dependent response. These transcriptional triggers include known and novel regulators that respond to carbon, nitrogen and oxygen limitation. Our analysis suggests a sequence of physiological responses, including a coupling between nitrogen depletion and glycogen storage, partially recapitulated through dynamic flux balance analysis, and experimentally confirmed by metabolite measurements. Our approach is broadly applicable to other systems PB - SISSA UR - http://hdl.handle.net/1963/6506 U1 - 6452 U2 - Mathematics U4 - 1 ER -