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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…
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…
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…
The major biochemical networks of the living cell, the network of interacting genes and the network of biochemical reactions, are highly interdependent, however, they have been studied mostly as separate systems so far. In the last years an…
We outline a modeling and optimization strategy for investigating dynamic metabolic engineering interventions. Our framework is particularly useful at the early stages of research and development, often constrained by limited knowledge and…
The metabolic network of a living cell involves several hundreds or thousands of interconnected biochemical reactions. Previous research has shown that under realistic conditions only a fraction of these reactions is concurrently active in…
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…
Accurately determining and classifying the structure of complex networks is the focus of much current research. One class of network of particular interest are metabolic pathways, which have previously been studied from a graph theoretical…
An important goal of medical research is to develop methods to recover the loss of cellular function due to mutations and other defects. Many approaches based on gene therapy aim to repair the defective gene or to insert genes with…
A metabolic model can be represented as bipartite graph comprising linked reaction and metabolite nodes. Here it is shown how a network of conserved fluxes can be assigned to the edges of such a graph by combining the reaction fluxes with a…
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…
We study a simplified, solvable model of a fully-connected metabolic network with constrained quenched disorder to mimic the conservation laws imposed by stoichiometry on chemical reactions. Within a spin-glass type of approach, we show…
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 reactions of single-cell organisms are routinely observed to become dispensable or even incapable of carrying activity under certain circumstances. Yet, the mechanisms as well as the range of conditions and phenotypes associated…
The rapidly developing theory of complex networks indicates that real networks are not random, but have a highly robust large-scale architecture, governed by strict organizational principles. Here, we focus on the properties of biological…
Recent research shows that a faulty or sub-optimally operating metabolic network can often be rescued by the targeted removal of enzyme-coding genes--the exact opposite of what traditional gene therapy would suggest. Predictions go as far…
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…
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…
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 networks play a crucial role in biology since they capture all chemical reactions in an organism. While there are networks of high quality for many model organisms, networks for less studied organisms are often of poor quality and…