608 research outputs found
Global entrainment of transcriptional systems to periodic inputs
This paper addresses the problem of giving conditions for transcriptional
systems to be globally entrained to external periodic inputs. By using
contraction theory, a powerful tool from dynamical systems theory, it is shown
that certain systems driven by external periodic signals have the property that
all solutions converge to a fixed limit cycle. General results are proved, and
the properties are verified in the specific case of some models of
transcriptional systems. The basic mathematical results needed from contraction
theory are proved in the paper, making it self-contained
Sensitivity analysis of circadian entrainment in the space of phase response curves
Sensitivity analysis is a classical and fundamental tool to evaluate the role
of a given parameter in a given system characteristic. Because the phase
response curve is a fundamental input--output characteristic of oscillators, we
developed a sensitivity analysis for oscillator models in the space of phase
response curves. The proposed tool can be applied to high-dimensional
oscillator models without facing the curse of dimensionality obstacle
associated with numerical exploration of the parameter space. Application of
this tool to a state-of-the-art model of circadian rhythms suggests that it can
be useful and instrumental to biological investigations.Comment: 22 pages, 8 figures. Correction of a mistake in Definition 2.1. arXiv
admin note: text overlap with arXiv:1206.414
Robustness from flexibility in the fungal circadian clock
Background
Robustness is a central property of living systems, enabling function to be maintained against environmental perturbations. A key challenge is to identify the structures in biological circuits that confer system-level properties such as robustness. Circadian clocks allow organisms to adapt to the predictable changes of the 24-hour day/night cycle by generating endogenous rhythms that can be entrained to the external cycle. In all organisms, the clock circuits typically comprise multiple interlocked feedback loops controlling the rhythmic expression of key genes. Previously, we showed that such architectures increase the flexibility of the clock's rhythmic behaviour. We now test the relationship between flexibility and robustness, using a mathematical model of the circuit controlling conidiation in the fungus Neurospora crassa.
Results
The circuit modelled in this work consists of a central negative feedback loop, in which the frequency (frq) gene inhibits its transcriptional activator white collar-1 (wc-1), interlocked with a positive feedback loop in which FRQ protein upregulates WC-1 production. Importantly, our model reproduces the observed entrainment of this circuit under light/dark cycles with varying photoperiod and cycle duration. Our simulations show that whilst the level of frq mRNA is driven directly by the light input, the falling phase of FRQ protein, a molecular correlate of conidiation, maintains a constant phase that is uncoupled from the times of dawn and dusk. The model predicts the behaviour of mutants that uncouple WC-1 production from FRQ's positive feedback, and shows that the positive loop enhances the buffering of conidiation phase against seasonal photoperiod changes. This property is quantified using Kitano's measure for the overall robustness of a regulated system output. Further analysis demonstrates that this functional robustness is a consequence of the greater evolutionary flexibility conferred on the circuit by the interlocking loop structure.
Conclusions
Our model shows that the behaviour of the fungal clock in light-dark cycles can be accounted for by a transcription-translation feedback model of the central FRQ-WC oscillator. More generally, we provide an example of a biological circuit in which greater flexibility yields improved robustness, while also introducing novel sensitivity analysis techniques applicable to a broader range of cellular oscillators
On Three Generalizations of Contraction
We introduce three forms of generalized contraction (GC). Roughly speaking,
these are motivated by allowing contraction to take place after small
transients in time and/or amplitude. Indeed, contraction is usually used to
prove asymptotic properties, like convergence to an attractor or entrainment to
a periodic excitation, and allowing initial transients does not affect this
asymptotic behavior.
We provide sufficient conditions for GC, and demonstrate their usefulness
using examples of systems that are not contractive, with respect to any norm,
yet are GC
Sensitivity analysis of oscillator models in the space of phase-response curves: Oscillators as open systems
Oscillator models are central to the study of system properties such as
entrainment or synchronization. Due to their nonlinear nature, few
system-theoretic tools exist to analyze those models. The paper develops a
sensitivity analysis for phase-response curves, a fundamental one-dimensional
phase reduction of oscillator models. The proposed theoretical and numerical
analysis tools are illustrated on several system-theoretic questions and models
arising in the biology of cellular rhythms
Global convergence of quorum-sensing networks
In many natural synchronization phenomena, communication between individual
elements occurs not directly, but rather through the environment. One of these
instances is bacterial quorum sensing, where bacteria release signaling
molecules in the environment which in turn are sensed and used for population
coordination. Extending this motivation to a general non- linear dynamical
system context, this paper analyzes synchronization phenomena in networks where
communication and coupling between nodes are mediated by shared dynamical quan-
tities, typically provided by the nodes' environment. Our model includes the
case when the dynamics of the shared variables themselves cannot be neglected
or indeed play a central part. Applications to examples from systems biology
illustrate the approach.Comment: Version 2: minor editions, added section on noise. Number of pages:
36
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