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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 -
Comparative profiling identifies C13orf3 as a component of the Ska complex required for mammalian cell division
(2009)The EMBO JournalJournal 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 -
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 -
An integrated workflow for charting the human interaction proteome: insights into the PP2A system
(2009)Molecular Systems BiologyProtein complexes represent major functional units for the execution of biological processes. Systematic affinity purification coupled with mass spectrometry (AP‐MS) yielded a wealth of information on the compendium of protein complexes expressed in Saccharomyces cerevisiae. However, global AP‐MS analysis of human protein complexes is hampered by the low throughput, sensitivity and data robustness of existing procedures, which limit its ...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 -
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 -
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