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Reproducible quantitative proteotype data matrices for systems biology
(2015)Molecular Biology of the CellHistorically, many mass spectrometry–based proteomic studies have aimed at compiling an inventory of protein compounds present in a biological sample, with the long-term objective of creating a proteome map of a species. However, to answer fundamental questions about the behavior of biological systems at the protein level, accurate and unbiased quantitative data are required in addition to a list of all protein components. Fueled by ...Journal Article -
Epigenetics and proteomics join transcriptomics in the quest for tuberculosis biomarkers
(2015)mBioAn estimated one-third of the world's population is currently latently infected with Mycobacterium tuberculosis. Latent M. tuberculosis infection (LTBI) progresses into active tuberculosis (TB) disease in ~5 to 10% of infected individuals. Diagnostic and prognostic biomarkers to monitor disease progression are urgently needed to ensure better care for TB patients and to decrease the spread of TB. Biomarker development is primarily based ...Journal Article -
Temporal system-level organization of the switch from glycolytic to gluconeogenic operation in yeast
(2013)Molecular Systems BiologyThe diauxic shift in Saccharomyces cerevisiae is an ideal model to study how eukaryotic cells readjust their metabolism from glycolytic to gluconeogenic operation. In this work, we generated time‐resolved physiological data, quantitative metabolome (69 intracellular metabolites) and proteome (72 enzymes) profiles. We found that the diauxic shift is accomplished by three key events that are temporally organized: (i) a reduction in the ...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 -
Interaction proteome of human Hippo signaling: modular control of the co-activator YAP1
(2013)Molecular Systems BiologyTissue homeostasis is controlled by signaling systems that coordinate cell proliferation, cell growth and cell shape upon changes in the cellular environment. Deregulation of these processes is associated with human cancer and can occur at multiple levels of the underlying signaling systems. To gain an integrated view on signaling modules controlling tissue growth, we analyzed the interaction proteome of the human Hippo pathway, an ...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 -
Insights into EB1 structure and the role of its C-terminal domain for discriminating microtubule tips from the lattice
(2011)Molecular Biology of the CellEnd-binding proteins (EBs) comprise a conserved family of microtubule plus end–tracking proteins. The concerted action of calponin homology (CH), linker, and C-terminal domains of EBs is important for their autonomous microtubule tip tracking, regulation of microtubule dynamics, and recruitment of numerous partners to microtubule ends. Here we report the detailed structural and biochemical analysis of mammalian EBs. Small-angle X-ray ...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 -
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