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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…

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…

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…

Cellular ingredient concentrations can be stabilized by adjusting generation and consumption rates through multiple pathways. To explore the portion of cellular metabolism equipped with multiple pathways, we categorize individual metabolic…

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…

Many of the chemical reactions that take place within a living cell are irreversible. Due to evolutionary pressures, the number of allowable reactions within these systems are highly constrained and thus the resulting metabolic networks…

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…

Understanding the system level adaptive changes taking place in an organism in response to variations in the environment is a key issue of contemporary biology. Current modeling approaches such as the constraint-based flux balance analyses…

Local perturbations of individual metabolic reactions may result in different levels of lethality, depending on their roles in metabolism and the size of subsequent cascades induced by their failure. Moreover, essentiality of individual…

Despite their topological complexity almost all functional properties of metabolic networks can be derived from steady-state dynamics. Indeed, many theoretical investigations (like flux-balance analysis) rely on extracting function from…

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…

In living cells, biochemical reactions are catalyzed by specific enzymes and connect to one another by sharing substrates and products, forming complex networks. In our previous studies, we established a framework determining the responses…

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…

Despite major environmental and genetic differences, microbial metabolic networks are known to generate consistent physiological outcomes across vastly different organisms. This remarkable robustness suggests that, at least in bacteria,…

In a cell or microorganism the processes that generate mass, energy, information transfer, and cell fate specification are seamlessly integrated through a complex network of various cellular constituents and reactions. However, despite the…

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…

Biological systems operate under simultaneous energetic and informational constraints, yet direct evidence that such constraints shape real metabolic networks is limited. The Network-Weighted Action Principle predicts that networks under…

Recently there has been a lot of interest in identifying modules at the level of genetic and metabolic networks of organisms, as well as in identifying single genes and reactions that are essential for the organism. A goal of computational…

Within a fully microscopic setting, we derive a variational principle for the non-equilibrium steady states of chemical reaction networks, valid for time-scales over which chemical potentials can be taken to be slowly varying: at…

Metabolic networks have two properties that are generally regarded as unrelated: One, they have metabolic reactions whose single knockout is lethal for the organism, and two, they have correlated sets of reactions forming functional…