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Dynamical Consequences of Bandpass Feedback Loops in a Bacterial Phosphorelay 英文参考文献.docVIP

Dynamical Consequences of Bandpass Feedback Loops in a Bacterial Phosphorelay 英文参考文献.doc

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Dynamical Consequences of Bandpass Feedback Loops in a Bacterial Phosphorelay 英文参考文献

DynamicalConsequencesofBandpassFeedbackLoops inaBacterialPhosphorelay ShaunakSen1,JordiGarcia-Ojalvo2,MichaelB.Elowitz3* 1DepartmentofControlandDynamicalSystems,DivisionofEngineeringandAppliedScience,CaliforniaInstituteofTechnology,Pasadena,California,UnitedStatesof America,2DepartamentdeFisicaiEnginyeriaNuclear,UniversitatPolitecnicadeCatalunya,Terrassa,Spain,3HowardHughesMedicalInstituteandDivisionofBiology, DepartmentofBioengineeringandAppliedPhysics,CaliforniaInstituteofTechnology,Pasadena,California,UnitedStatesofAmerica Abstract Underconditionsofnutrientlimitation,Bacillussubtiliscellsterminallydifferentiateintoadormantsporestate.Progression tosporulationiscontrolledbyageneticcircuitconsistingofaphosphorelayembeddedinmultipletranscriptionalfeedback loops, which is used to activate the master regulator Spo0A by phosphorylation. These transcriptional regulatory interactions are ‘‘bandpass’’-like, in the sense that activation occurs within a limited band of Spo0A, P concentrations. Additionally, recent results show that the phosphorelay activation occurs in pulses, in a cell-cycle dependent fashion. However,theimpactofthesepulsedbandpassinteractionsonthecircuitdynamicsprecedingsporulationremainsunclear. In order to address this question, we measured key features of the bandpass interactions at the single-cell level and analyzedtheminthecontextofasimplemathematicalmodel.Themodelpredictedtheemergenceofadelayedphaseshift between the pulsing activity of the different sporulation genes, as well as the existence of a stable state, with elevated Spo0Aactivitybutnosporulation,embeddedwithinthedynamicalstructureofthesystem.Totestthemodel,weused time-lapse fluorescence microscopy to measure dynamics of single cells initiating sporulation. We observed the delayed phase shift emerging during the progression to sporulation, while a re-engineering of the sporulation circuit revealed behaviorresemblingthepredictedadditionalstate.Theseresultsshowthatperiodically-drivenbandpass

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