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The heterogeneity of reaction fluxes present in a metabolic network within a single flux state can be exploited to construct the so-called backbone as a reduced version of metabolism. The backbone maintains all significant fluxes producing…
Cellular metabolism, the integrated interconversion of thousands of metabolic substrates through enzyme-catalyzed biochemical reactions, is the most investigated complex intercellular web of molecular interactions. While the topological…
Genome-scale metabolic models have become a fundamental tool for examining metabolic principles. However, metabolism is not solely characterized by the underlying biochemical reactions and catalyzing enzymes, but also affected by regulatory…
We have created a genome-scale network reconstruction of Escherichia coli metabolism. Existing reconstructions were improved in terms of annotation standards, to facilitate their subsequent use in dynamic modelling. The resultant network is…
Understanding the organization of reaction fluxes in cellular metabolism from the stoichiometry and the topology of the underlying biochemical network is a central issue in systems biology. In this task, it is important to devise reasonable…
Social interaction between microbes can be described at many levels of details, ranging from the biochemistry of cell-cell interactions to the ecological dynamics of populations. Choosing the best level to model microbial communities…
Biological systems are governed by coupled interactions between intracellular metabolism and bioreactor operation that span multiple time scales. Constraint-based metabolic models are widely used to describe intracellular metabolism, but…
The integration of various types of genomic data into predictive models of biological networks is one of the main challenges currently faced by computational biology. Constraint-based models in particular play a key role in the attempt to…
The stoichiometry of metabolic networks usually gives rise to a family of conservation laws for the aggregate concentration of specific pools of metabolites, which not only constrain the dynamics of the network, but also provide key insight…
The solution space of genome-scale models of cellular metabolism provides a map between physically viable flux configurations and cellular metabolic phenotypes described, at the most basic level, by the corresponding growth rates. By…
Reliability on complex biological networks reconstructions remains a concern. Although observations are getting more and more precise, the data collection process is yet error prone and the proofs display uneven certitude. In the case of…
Complex biological systems are very robust to genetic and environmental changes at all levels of organization. Many biological functions of Escherichia coli metabolism can be sustained against single-gene or even multiple-gene mutations by…
Metabolic scaling is one of the most important patterns in biology. Theory explaining the 3/4-power size-scaling of biological metabolic rate does not predict the non-linear scaling observed for smaller life forms. Here we present a new…
In this thesis, we have studied the large scale structure and system level dynamics of certain biological networks using tools from graph theory, computational biology and dynamical systems. We study the structure and dynamics of large…
Metabolic pathways describe chains of enzymatic reactions. Their modelling is a key point to understand living systems. An enzymatic reaction is an interaction between one or several metabolites (substrates) and an enzyme (simple protein or…
Genome-scale metabolic models (GEMs) are essential tools for systems biology and rational chassis design, but conventional top-down reconstruction depends heavily on sequence homology and often leaves unknown enzymes and metabolic dark…
Elucidating the architecture and dynamics of large scale genetic regulatory networks of cells is an important goal in systems biology. We study the system level dynamical properties of the genetic network of Escherichia coli that regulates…
Deciphering the control principles of metabolism and its interaction with other cellular functions is central to biomedicine and biotechnology. Yet, understanding the efficient control of metabolic fluxes remains elusive for large-scale…
The metabolic network plays a crucial role in regulating bacterial metabolism and growth, but it is subject to inherent molecular stochasticity. Previous studies have utilized flux balance analysis and the maximum entropy method to predict…
Recent work on synthetic rescues has shown that the targeted deletion of specific metabolic genes can often be used to rescue otherwise non-viable mutants. This raises a fundamental biophysical question: to what extent can the whole-cell…