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Systems approaches to modelling pathways and networks.
Peer reviewedPreprin
The solution space of metabolic networks: producibility, robustness and fluctuations
Flux analysis is a class of constraint-based approaches to the study of
biochemical reaction networks: they are based on determining the reaction flux
configurations compatible with given stoichiometric and thermodynamic
constraints. One of its main areas of application is the study of cellular
metabolic networks. We briefly and selectively review the main approaches to
this problem and then, building on recent work, we provide a characterization
of the productive capabilities of the metabolic network of the bacterium E.coli
in a specified growth medium in terms of the producible biochemical species.
While a robust and physiologically meaningful production profile clearly
emerges (including biomass components, biomass products, waste etc.), the
underlying constraints still allow for significant fluctuations even in key
metabolites like ATP and, as a consequence, apparently lay the ground for very
different growth scenarios.Comment: 10 pages, prepared for the Proceedings of the International Workshop
on Statistical-Mechanical Informatics, March 7-10, 2010, Kyoto, Japa
The Dynamics of Hybrid Metabolic-Genetic Oscillators
The synthetic construction of intracellular circuits is frequently hindered
by a poor knowledge of appropriate kinetics and precise rate parameters. Here,
we use generalized modeling (GM) to study the dynamical behavior of topological
models of a family of hybrid metabolic-genetic circuits known as
"metabolators." Under mild assumptions on the kinetics, we use GM to
analytically prove that all explicit kinetic models which are topologically
analogous to one such circuit, the "core metabolator," cannot undergo Hopf
bifurcations. Then, we examine more detailed models of the metabolator.
Inspired by the experimental observation of a Hopf bifurcation in a
synthetically constructed circuit related to the core metabolator, we apply GM
to identify the critical components of the synthetically constructed
metabolator which must be reintroduced in order to recover the Hopf
bifurcation. Next, we study the dynamics of a re-wired version of the core
metabolator, dubbed the "reverse" metabolator, and show that it exhibits a
substantially richer set of dynamical behaviors, including both local and
global oscillations. Prompted by the observation of relaxation oscillations in
the reverse metabolator, we study the role that a separation of genetic and
metabolic time scales may play in its dynamics, and find that widely separated
time scales promote stability in the circuit. Our results illustrate a generic
pipeline for vetting the potential success of a potential circuit design,
simply by studying the dynamics of the corresponding generalized model
Editorial overview: recent innovations in the metabolomics revolution
No abstract available
Challenges in experimental data integration within genome-scale metabolic models
A report of the meeting "Challenges in experimental data integration within
genome-scale metabolic models", Institut Henri Poincar\'e, Paris, October 10-11
2009, organized by the CNRS-MPG joint program in Systems Biology.Comment: 5 page
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