23,285 research outputs found
Collective oscillation period of inter-coupled biological negative cyclic feedback oscillators
A number of biological rhythms originate from networks comprised of multiple
cellular oscillators. But analytical results are still lacking on the
collective oscillation period of inter-coupled gene regulatory oscillators,
which, as has been reported, may be different from that of an autonomous
oscillator. Based on cyclic feedback oscillators, we analyze the collective
oscillation pattern of coupled cellular oscillators. First we give a condition
under which the oscillator network exhibits oscillatory and synchronized
behavior. Then we estimate the collective oscillation period based on a novel
multivariable harmonic balance technique. Analytical results are derived in
terms of biochemical parameters, thus giving insight into the basic mechanism
of biological oscillation and providing guidance in synthetic biology design.Comment: arXiv admin note: substantial text overlap with arXiv:1203.125
Mechanical and Systems Biology of Cancer
Mechanics and biochemical signaling are both often deregulated in cancer,
leading to cancer cell phenotypes that exhibit increased invasiveness,
proliferation, and survival. The dynamics and interactions of cytoskeletal
components control basic mechanical properties, such as cell tension,
stiffness, and engagement with the extracellular environment, which can lead to
extracellular matrix remodeling. Intracellular mechanics can alter signaling
and transcription factors, impacting cell decision making. Additionally,
signaling from soluble and mechanical factors in the extracellular environment,
such as substrate stiffness and ligand density, can modulate cytoskeletal
dynamics. Computational models closely integrated with experimental support,
incorporating cancer-specific parameters, can provide quantitative assessments
and serve as predictive tools toward dissecting the feedback between signaling
and mechanics and across multiple scales and domains in tumor progression.Comment: 18 pages, 3 figure
Energy consumption and cooperation for optimal sensing
The reliable detection of environmental molecules in the presence of noise is
an important cellular function, yet the underlying computational mechanisms are
not well understood. We introduce a model of two interacting sensors which
allows for the principled exploration of signal statistics, cooperation
strategies and the role of energy consumption in optimal sensing, quantified
through the mutual information between the signal and the sensors. Here we
report that in general the optimal sensing strategy depends both on the noise
level and the statistics of the signals. For joint, correlated signals, energy
consuming (nonequilibrium), asymmetric couplings result in maximum information
gain in the low-noise, high-signal-correlation limit. Surprisingly we also find
that energy consumption is not always required for optimal sensing. We
generalise our model to incorporate time integration of the sensor state by a
population of readout molecules, and demonstrate that sensor interaction and
energy consumption remain important for optimal sensing.Comment: 9 pages, 5 figures, Forthcoming in Nature Communication
Theory on the Dynamics of Oscillatory Loops in the Transcription Factor Networks
We develop a detailed theoretical framework for various types of
transcription factor gene oscillators. We further demonstrate that one can
build genetic-oscillators which are tunable and robust against perturbations in
the critical control parameters by coupling two or more independent
Goodwin-Griffith oscillators through either -OR- or -AND- type logic. Most of
the coupled oscillators constructed in the literature so far seem to be of -OR-
type. When there are transient perturbations in one of the -OR- type
coupled-oscillators, then the overall period of the system remains constant
(period-buffering) whereas in case of -AND- type coupling the overall period of
the system moves towards the perturbed oscillator. Though there is a
period-buffering, the amplitudes of oscillators coupled through -OR- type logic
are more sensitive to perturbations in the parameters associated with the
promoter state dynamics than -AND- type. Further analysis shows that the period
of -AND- type coupled dual-feedback oscillators can be tuned without conceding
on the amplitudes. Using these results we derive the basic design principles
governing the robust and tunable synthetic gene oscillators without
compromising on their amplitudes.Comment: 37 pages, 13 figures, 2 table
Contextualizing context for synthetic biology--identifying causes of failure of synthetic biological systems.
Despite the efforts that bioengineers have exerted in designing and constructing biological processes that function according to a predetermined set of rules, their operation remains fundamentally circumstantial. The contextual situation in which molecules and single-celled or multi-cellular organisms find themselves shapes the way they interact, respond to the environment and process external information. Since the birth of the field, synthetic biologists have had to grapple with contextual issues, particularly when the molecular and genetic devices inexplicably fail to function as designed when tested in vivo. In this review, we set out to identify and classify the sources of the unexpected divergences between design and actual function of synthetic systems and analyze possible methodologies aimed at controlling, if not preventing, unwanted contextual issues
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