02153nas a2200181   4500008004100000245015200041210006900193260001000262520154500272100001101817700002101828700001601849700001501865700001401880700001901894700002201913856003601935       2012                        en  d00aDetection of transcriptional triggers in the dynamics of microbial growth: application to the respiratory-versatile bacterium Shewanella oneidensis0 aDetection of transcriptional triggers in the dynamics of microbi  bSISSA3 aThe 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 systems1 aBeg, Q1 aZampieri, Mattia1 aKlitgord, N1 aCollins, S1 aSerres, M1 aSegrè, Daniel1 aAltafini, Claudio  uhttp://hdl.handle.net/1963/6506