Related papers: Multi-scale Metabolic Modeling and Simulation
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…
Metabolic cybergenetics is a promising concept that interfaces gene expression and cellular metabolism with computers for real-time dynamic metabolic control. The focus is on control at the transcriptional level, serving as a means to…
Flux balance analysis has proven an effective tool for analyzing metabolic networks. In flux balance analysis, reaction rates and optimal pathways are ascertained by solving a linear program, in which the growth rate is maximized subject to…
Current mathematical frameworks for predicting the flux state and macromolecular composition of the cell do not rely on thermodynamic constraints to determine the spontaneous direction of reactions. These predictions may be biologically…
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…
Biotechnology offers many opportunities for the sustainable manufacturing of valuable products. The toolbox to optimize bioprocesses includes \textit{extracellular} process elements such as the bioreactor design and mode of operation,…
Optimization-based models have been used to predict cellular behavior for over 25 years. The constraints in these models are derived from genome annotations, measured macro-molecular composition of cells, and by measuring the cell's growth…
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…
Metabolic heterogeneity is widely recognised as the next challenge in our understanding of non-genetic variation. A growing body of evidence suggests that metabolic heterogeneity may result from the inherent stochasticity of intracellular…
The regulation of metabolic activity by tuning enzyme expression levels is crucial to sustain cellular growth in changing environments. Metabolic networks are often studied at steady state using constraint-based models and optimization…
Metabolic models condense biochemical knowledge about organisms in a structured and standardised way. As large-scale network reconstructions are readily available for many organisms, genome-scale models are being widely used among modellers…
We present a model for continuous cell culture coupling intra-cellular metabolism to extracellular variables describing the state of the bioreactor, taking into account the growth capacity of the cell and the impact of toxic byproduct…
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…
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…
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 advancement of human healthspan and bioengineering relies heavily on predicting the behavior of complex biological systems. While high-throughput multiomics data is becoming increasingly abundant, converting this data into actionable…
A major goal of modern computational biology is to simulate the collective behaviour of large cell populations starting from the intricate web of molecular interactions occurring at the microscopic level. In this paper we describe a…
The central task in modeling complex dynamical systems is parameter estimation. This task involves numerous evaluations of a computationally expensive objective function. Surrogate-based optimization introduces a computationally efficient…
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…
Living organisms rely on endogenous feedback mechanisms to maintain homeostasis in the presence of uncertainty and environmental fluctuations. An emerging challenge at the interface of control systems engineering and synthetic biology is…