Phosphoproteomic analyses reveal novel cross-modulation mechanisms between two signaling pathways in yeast
Cells respond to environmental stimuli via specialized signaling pathways. Concurrent stimuli trigger multiple pathways that integrate information, predominantly via protein phosphorylation. Budding yeast responds to NaCl and pheromone via two mitogen-activated protein kinase cascades, the high osmolarity, and the mating pathways, respectively. To investigate signal integration between these pathways, we quantified the time-resolved phosphorylation site dynamics after pathway co-stimulation. Using shotgun mass spectrometry, we quantified 2,536 phosphopeptides across 36 conditions. Our data indicate that NaCl and pheromone ...
Source: Molecular Systems Biology - December 9, 2014 Category: Molecular Biology Authors: Vaga, S., Bernardo-Faura, M., Cokelaer, T., Maiolica, A., Barnes, C. A., Gillet, L. C., Hegemann, B., van Drogen, F., Sharifian, H., Klipp, E., Peter, M., Saez-Rodriguez, J., Aebersold, R. Tags: Genome-Scale & Integrative Biology, Post-translational Modifications, Proteolysis & Proteomics, Signal Transduction Articles Source Type: research
Potential of fecal microbiota for early-stage detection of colorectal cancer
Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy ...
Source: Molecular Systems Biology - November 28, 2014 Category: Molecular Biology Authors: Zeller, G., Tap, J., Voigt, A. Y., Sunagawa, S., Kultima, J. R., Costea, P. I., Amiot, A., Bohm, J., Brunetti, F., Habermann, N., Hercog, R., Koch, M., Luciani, A., Mende, D. R., Schneider, M. A., Schrotz-King, P., Tournigand, C., Tran Van Nhieu, J., Yama Tags: Cancer, Systems Medicine Articles Source Type: research
Natural genetic variation impacts expression levels of coding, non-coding, and antisense transcripts in fission yeast
Our current understanding of how natural genetic variation affects gene expression beyond well-annotated coding genes is still limited. The use of deep sequencing technologies for the study of expression quantitative trait loci (eQTLs) has the potential to close this gap. Here, we generated the first recombinant strain library for fission yeast and conducted an RNA-seq-based QTL study of the coding, non-coding, and antisense transcriptomes. We show that the frequency of distal effects (trans-eQTLs) greatly exceeds the number of local effects (cis-eQTLs) and that non-coding RNAs are as likely to be affected by eQTLs as prot...
Source: Molecular Systems Biology - November 28, 2014 Category: Molecular Biology Authors: Clement-Ziza, M., Marsellach, F. X., Codlin, S., Papadakis, M. A., Reinhardt, S., Rodriguez-Lopez, M., Martin, S., Marguerat, S., Schmidt, A., Lee, E., Workman, C. T., Bahler, J., Beyer, A. Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Transcription Articles Source Type: research
Protein acetylation affects acetate metabolism, motility and acid stress response in Escherichia coli
Although protein acetylation is widely observed, it has been associated with few specific regulatory functions making it poorly understood. To interrogate its functionality, we analyzed the acetylome in Escherichia coli knockout mutants of cobB, the only known sirtuin-like deacetylase, and patZ, the best-known protein acetyltransferase. For four growth conditions, more than 2,000 unique acetylated peptides, belonging to 809 proteins, were identified and differentially quantified. Nearly 65% of these proteins are related to metabolism. The global activity of CobB contributes to the deacetylation of a large number of substra...
Source: Molecular Systems Biology - November 27, 2014 Category: Molecular Biology Authors: Castano-Cerezo, S., Bernal, V., Post, H., Fuhrer, T., Cappadona, S., Sanchez-Diaz, N. C., Sauer, U., Heck, A. J., Altelaar, A. M., Canovas, M. Tags: Microbiology, Virology & Host Pathogen Interaction, Post-translational Modifications, Proteolysis & Proteomics Articles Source Type: research
A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration
(Source: Molecular Systems Biology)
Source: Molecular Systems Biology - November 27, 2014 Category: Molecular Biology Authors: Yizhak, K., Le Devedec, S. E., Rogkoti, V. M., Baenke, F., de Boer, V. C., Frezza, C., Schulze, A., van de Water, B., Ruppin, E. Tags: Addendum Source Type: research
Multi-input CRISPR/Cas genetic circuits that interface host regulatory networks
Genetic circuits require many regulatory parts in order to implement signal processing or execute algorithms in cells. A potentially scalable approach is to use dCas9, which employs small guide RNAs (sgRNAs) to repress genetic loci via the programmability of RNA:DNA base pairing. To this end, we use dCas9 and designed sgRNAs to build transcriptional logic gates and connect them to perform computation in living cells. We constructed a set of NOT gates by designing five synthetic Escherichia coli 70 promoters that are repressed by corresponding sgRNAs, and these interactions do not exhibit crosstalk between each other. These...
Source: Molecular Systems Biology - November 24, 2014 Category: Molecular Biology Authors: Nielsen, A. A., Voigt, C. A. Tags: Methods & Resources, Synthetic Biology & Biotechnology Articles Source Type: research
Systematic identification of cell size regulators in budding yeast
Cell size is determined by a complex interplay between growth and division, involving multiple cellular pathways. To identify systematically processes affecting size control in G1 in budding yeast, we imaged and analyzed the cell cycle of millions of individual cells representing 591 mutants implicated in size control. Quantitative metric distinguished mutants affecting the mechanism of size control from the majority of mutants that have a perturbed size due to indirect effects modulating cell growth. Overall, we identified 17 negative and dozens positive size control regulators, with the negative regulators forming a smal...
Source: Molecular Systems Biology - November 19, 2014 Category: Molecular Biology Authors: Soifer, I., Barkai, N. Tags: Cell Cycle, Genome-Scale & Integrative Biology Articles Source Type: research
