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Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis
(2013)Molecular Systems BiologyOne of the key ways in which microbes are thought to regulate their metabolism is by modulating the availability of enzymes through transcriptional regulation. However, the limited success of efforts to manipulate metabolic fluxes by rewiring the transcriptional network has cast doubt on the idea that transcript abundance controls metabolic fluxes. In this study, we investigate control of metabolic flux in the model bacterium Bacillus ...Journal Article -
Systems-based analysis of Arabidopsis leaf growth reveals adaptation to water deficit
(2012)Molecular Systems BiologyLeaves have a central role in plant energy capture and carbon conversion and therefore must continuously adapt their development to prevailing environmental conditions. To reveal the dynamic systems behaviour of leaf development, we profiled Arabidopsis leaf number six in depth at four different growth stages, at both the end‐of‐day and end‐of‐night, in plants growing in two controlled experimental conditions: short‐day conditions with ...Journal Article -
Regulation of yeast central metabolism by enzyme phosphorylation
(2012)Molecular Systems BiologyAs a frequent post‐translational modification, protein phosphorylation regulates many cellular processes. Although several hundred phosphorylation sites have been mapped to metabolic enzymes in Saccharomyces cerevisiae, functionality was demonstrated for few of them. Here, we describe a novel approach to identify in vivo functionality of enzyme phosphorylation by combining flux analysis with proteomics and phosphoproteomics. Focusing on ...Journal Article -
Controlled vocabularies and semantics in systems biology
(2011)Molecular Systems BiologyThe use of computational modeling to describe and analyze biological systems is at the heart of systems biology. Model structures, simulation descriptions and numerical results can be encoded in structured formats, but there is an increasing need to provide an additional semantic layer. Semantic information adds meaning to components of structured descriptions to help identify and interpret them unambiguously. Ontologies are one of the ...Journal Article -
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