Phase resetting reveals network dynamics underlying a bacterial cell cycle

Genomic and proteomic methods yield networks of biological regulatory interactions but do not provide direct insight into how those interactions are organized into functional modules, or how information flows from one module to another. In this work we introduce an approach that provides this complementary information and apply it to the bacterium Caulobacter crescentus, a paradigm for cell-cycle control. Operationally, we use an inducible promoter to express the essential transcriptional regulatory gene ctrA in a periodic, pulsed fashion. This chemical perturbation causes the population of cells to divide synchronously, and we use the resulting advance or delay of the division times of single cells to construct a phase resetting curve. We find that delay is strongly favored over advance. This finding is surprising since it does not follow from the temporal expression profile of CtrA and, in turn, simulations of existing network models. We propose a phenomenological model that suggests that the cell-cycle network comprises two distinct functional modules that oscillate autonomously and couple in a highly asymmetric fashion. These features collectively provide a new mechanism for tight temporal control of the cell cycle in C. crescentus. We discuss how the procedure can serve as the basis for a general approach for probing network dynamics, which we term chemical perturbation spectroscopy (CPS)

Emergence and combinatorial accumulation of jittering regimes in spiking oscillators with delayed feedback

Interaction via pulses is common in many natural systems, especially neuronal. In this article we study one of the simplest possible systems with pulse interaction: a phase oscillator with delayed pulsatile feedback. When the oscillator reaches a specific state, it emits a pulse, which returns after propagating through a delay line. The impact of an incoming pulse is described by the oscillator's phase reset curve (PRC). In such a system we discover an unexpected phenomenon: for a sufficiently steep slope of the PRC, a periodic regular spiking solution bifurcates with several multipliers crossing the unit circle at the same parameter value. The number of such critical multipliers increases linearly with the delay and thus may be arbitrary large. This bifurcation is accompanied by the emergence of numerous "jittering" regimes with non-equal interspike intervals (ISIs). Each of these regimes corresponds to a periodic solution of the system with a period roughly proportional to the delay. The number of different "jittering" solutions emerging at the bifurcation point increases exponentially with the delay. We describe the combinatorial mechanism that underlies the emergence of such a variety of solutions. In particular, we show how a periodic solution exhibiting several distinct ISIs can imply the existence of multiple other solutions obtained by rearranging of these ISIs. We show that the theoretical results for phase oscillators accurately predict the behavior of an experimentally implemented electronic oscillator with pulsatile feedback

Nonlinear transient waves in coupled phase oscillators with inertia

Like the inertia of a physical body describes its tendency to resist changes of its state of motion, inertia of an oscillator describes its tendency to resist changes of its frequency. Here we show that finite inertia of individual oscillators enables nonlinear phase waves in spatially extended coupled systems. Using a discrete model of coupled phase oscillators with inertia, we investigate these wave phenomena numerically, complemented by a continuum approximation that permits the analytical description of the key features of wave propagation in the long-wavelength limit. The ability to exhibit traveling waves is a generic feature of systems with finite inertia and is independent of the details of the coupling function.Comment: 12 pages, 4 figure