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Absolute quantification of microbial proteomes at different states by directed mass spectrometry
(2011)Molecular Systems BiologyOver the past decade, liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) has evolved into the main proteome discovery technology. Up to several thousand proteins can now be reliably identified from a sample and the relative abundance of the identified proteins can be determined across samples. However, the remeasurement of substantially similar proteomes, for example those generated by perturbation experiments in systems ...Journal Article -
Bacterial adaptation through distributed sensing of metabolic fluxes
(2010)Molecular Systems BiologyThe recognition of carbon sources and the regulatory adjustments to recognized changes are of particular importance for bacterial survival in fluctuating environments. Despite a thorough knowledge base of Escherichia coli's central metabolism and its regulation, fundamental aspects of the employed sensing and regulatory adjustment mechanisms remain unclear. In this paper, using a differential equation model that couples enzymatic and ...Journal Article -
Timescales and bottlenecks in miRNA-dependent gene regulation
(2013)Molecular Systems BiologyMiRNAs are post‐transcriptional regulators that contribute to the establishment and maintenance of gene expression patterns. Although their biogenesis and decay appear to be under complex control, the implications of miRNA expression dynamics for the processes that they regulate are not well understood. We derived a mathematical model of miRNA‐mediated gene regulation, inferred its parameters from experimental data sets, and found that ...Journal Article -
Targeted proteomics reveals strain-specific changes in the mouse insulin and central metabolic pathways after a sustained high-fat diet
(2013)Molecular Systems BiologyThe metabolic syndrome is a collection of risk factors including obesity, insulin resistance and hepatic steatosis, which occur together and increase the risk of diseases such as diabetes, cardiovascular disease and cancer. In spite of intense research, the complex etiology of insulin resistance and its association with the accumulation of triacylglycerides in the liver and with hepatic steatosis remains not completely understood. Here, ...Journal Article -
Biomedically relevant circuit-design strategies in mammalian synthetic biology
(2013)Molecular Systems BiologyThe development and progress in synthetic biology has been remarkable. Although still in its infancy, synthetic biology has achieved much during the past decade. Improvements in genetic circuit design have increased the potential for clinical applicability of synthetic biology research. What began as simple transcriptional gene switches has rapidly developed into a variety of complex regulatory circuits based on the transcriptional, ...Journal Article -
Cell-cycle regulation of NOTCH signaling during C. elegans vulval development
(2012)Molecular Systems BiologyC. elegans vulval development is one of the best‐characterized systems to study cell fate specification during organogenesis. The detailed knowledge of the signaling pathways determining vulval precursor cell (VPC) fates permitted us to create a computational model based on the antagonistic interactions between the epidermal growth factor receptor (EGFR)/RAS/MAPK and the NOTCH pathways that specify the primary and secondary fates, ...Journal Article -
Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity
(2010)Molecular Systems BiologyWhat is the relationship between enzymes and metabolites, the two major constituents of metabolic networks? We propose three alternative relationships between enzyme capacity and metabolite concentration alterations based on a Michaelis–Menten kinetic; that is enzyme capacities, metabolite concentrations, or both could limit the metabolic reaction rates. These relationships imply different correlations between changes in enzyme capacity ...Journal Article -
Large-scale 13C-flux analysis reveals distinct transcriptional control of respiratory and fermentative metabolism in Escherichia coli
(2011)Molecular Systems BiologyDespite our increasing topological knowledge on regulation networks in model bacteria, it is largely unknown which of the many co‐occurring regulatory events actually control metabolic function and the distribution of intracellular fluxes. Here, we unravel condition‐dependent transcriptional control of Escherichia coli metabolism by large‐scale 13C‐flux analysis in 91 transcriptional regulator mutants on glucose and galactose. In contrast ...Journal Article -
The quantitative proteome of a human cell line
(2011)Molecular Systems BiologyThe generation of mathematical models of biological processes, the simulation of these processes under different conditions, and the comparison and integration of multiple data sets are explicit goals of systems biology that require the knowledge of the absolute quantity of the system's components. To date, systematic estimates of cellular protein concentrations have been exceptionally scarce. Here, we provide a quantitative description ...Journal Article -
Comprehensive quantitative analysis of central carbon and amino-acid metabolism in Saccharomyces cerevisiae under multiple conditions by targeted proteomics
(2011)Molecular Systems BiologyDecades of biochemical research have identified most of the enzymes that catalyze metabolic reactions in the yeast Saccharomyces cerevisiae. The adaptation of metabolism to changing nutritional conditions, in contrast, is much less well understood. As an important stepping stone toward such understanding, we exploit the power of proteomics assays based on selected reaction monitoring (SRM) mass spectrometry to quantify abundance changes ...Journal Article