Olfactory sensory neurons transiently express multiple olfactory receptors during development
In mammals, each olfactory sensory neuron randomly expresses one, and only one, olfactory receptor (OR)—a phenomenon called the "one-neuron-one-receptor" rule. Although extensively studied, this rule was never proven for all ~1,000 OR genes in one cell at once, and little is known about its dynamics. Here, we directly tested this rule by single-cell transcriptomic sequencing of 178 cells from the main olfactory epithelium of adult and newborn mice. To our surprise, a subset of cells expressed multiple ORs. Most of these cells were developmentally immature. Our results illustrated how the "one-neuron-one-receptor" rul...
Source: Molecular Systems Biology - December 8, 2015 Category: Molecular Biology Authors: Tan, L., Li, Q., Xie, X. S. Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Genome-Scale & Integrative Biology, Neuroscience Reports Source Type: research
Signaling output: it's all about timing and feedbacks
The central questions in understanding signaling pathway specificity are how these pathways encode which stimulus is present and how this stimulus is decoded to yield the correct cell fate decision. In their recent work, Ryu et al (2015) show by stimulation experiments with different ligands how the differential engagement of feedback and feed-forward regulation leads to different dynamics of pathway activity, which in turn alters cell fate. Moreover, they show that by considering the timescales of the feedback regulations, the different cellular responses can be triggered with pulsed stimulations by a single ligand. (Sour...
Source: Molecular Systems Biology - November 27, 2015 Category: Molecular Biology Authors: Blüthgen, N. Tags: Development & Differentiation, Quantitative Biology & Dynamical Systems, Signal Transduction News [amp ] Views Source Type: research
Frequency modulation of ERK activation dynamics rewires cell fate
Transient versus sustained ERK MAP kinase (MAPK) activation dynamics induce proliferation versus differentiation in response to epidermal (EGF) or nerve (NGF) growth factors in PC-12 cells. Duration of ERK activation has therefore been proposed to specify cell fate decisions. Using a biosensor to measure ERK activation dynamics in single living cells reveals that sustained EGF/NGF application leads to a heterogeneous mix of transient and sustained ERK activation dynamics in distinct cells of the population, different than the population average. EGF biases toward transient, while NGF biases toward sustained ERK activation ...
Source: Molecular Systems Biology - November 27, 2015 Category: Molecular Biology Authors: Ryu, H., Chung, M., Dobrzynski, M., Fey, D., Blum, Y., Lee, S. S., Peter, M., Kholodenko, B. N., Jeon, N. L., Pertz, O. Tags: Development & Differentiation, Quantitative Biology & Dynamical Systems, Signal Transduction Articles Source Type: research
A synthetic growth switch based on controlled expression of RNA polymerase
We present an application of the growth switch in which both the wild-type E. coli strain and our modified strain are endowed with the capacity to produce glycerol when growing on glucose. Cells in which growth has been switched off continue to be metabolically active and harness the energy gain to produce glycerol at a twofold higher yield than in cells with natural control of RNA polymerase expression. Remarkably, without any further optimization, the improved yield is close to the theoretical maximum computed from a flux balance model of E. coli metabolism. The proposed synthetic growth switch is a promising t...
Source: Molecular Systems Biology - November 23, 2015 Category: Molecular Biology Authors: Izard, J., Gomez Balderas, C. D., Ropers, D., Lacour, S., Song, X., Yang, Y., Lindner, A. B., Geiselmann, J., de Jong, H. Tags: Metabolism, Quantitative Biology & Dynamical Systems, Synthetic Biology & Biotechnology Articles Source Type: research
An experimentally supported model of the Bacillus subtilis global transcriptional regulatory network
Organisms from all domains of life use gene regulation networks to control cell growth, identity, function, and responses to environmental challenges. Although accurate global regulatory models would provide critical evolutionary and functional insights, they remain incomplete, even for the best studied organisms. Efforts to build comprehensive networks are confounded by challenges including network scale, degree of connectivity, complexity of organism–environment interactions, and difficulty of estimating the activity of regulatory factors. Taking advantage of the large number of known regulatory interactions in Bac...
Source: Molecular Systems Biology - November 17, 2015 Category: Molecular Biology Authors: Arrieta-Ortiz, M. L., Hafemeister, C., Bate, A. R., Chu, T., Greenfield, A., Shuster, B., Barry, S. N., Gallitto, M., Liu, B., Kacmarczyk, T., Santoriello, F., Chen, J., Rodrigues, C. D., Sato, T., Rudner, D. Z., Driks, A., Bonneau, R., Eichenberger, P. Tags: Genome-Scale & Integrative Biology, Network Biology, Transcription Articles Source Type: research
Systematic discovery of linear binding motifs targeting an ancient protein interaction surface on MAP kinases
Mitogen-activated protein kinases (MAPK) are broadly used regulators of cellular signaling. However, how these enzymes can be involved in such a broad spectrum of physiological functions is not understood. Systematic discovery of MAPK networks both experimentally and in silico has been hindered because MAPKs bind to other proteins with low affinity and mostly in less-characterized disordered regions. We used a structurally consistent model on kinase-docking motif interactions to facilitate the discovery of short functional sites in the structurally flexible and functionally under-explored part of the human proteome and app...
Source: Molecular Systems Biology - November 3, 2015 Category: Molecular Biology Authors: Zeke, A., Bastys, T., Alexa, A., Garai, A., Meszaros, B., Kirsch, K., Dosztanyi, Z., Kalinina, O. V., Remenyi, A. Tags: Computational Biology, Signal Transduction, Structural Biology Articles Source Type: research
Inflating bacterial cells by increased protein synthesis
We report that cell size and mass exhibit positive or negative dependences with growth rate depending on the growth limitation applied. In particular, synthesizing large amounts of "useless" proteins led to an inversion of the canonical, positive relation, with slow growing cells enlarged 7- to 8-fold compared to cells growing at similar rates under nutrient limitation. Strikingly, this increase in cell size was accompanied by a 3- to 4-fold increase in cellular DNA content at slow growth, reaching up to an amount equivalent to ~8 chromosomes per cell. Despite drastic changes in cell mass and macromolecular compositio...
Source: Molecular Systems Biology - October 30, 2015 Category: Molecular Biology Authors: Basan, M., Zhu, M., Dai, X., Warren, M., Sevin, D., Wang, Y.-P., Hwa, T. Tags: Metabolism, Protein Biosynthesis & Quality Control, Quantitative Biology & Dynamical Systems Reports Source Type: research
Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-{alpha}-induced apoptosis in vivo
Understanding heterogeneous cellular behaviors in a complex tissue requires the evaluation of signaling networks at single-cell resolution. However, probing signaling in epithelial tissues using cytometry-based single-cell analysis has been confounded by the necessity of single-cell dissociation, where disrupting cell-to-cell connections inherently perturbs native cell signaling states. Here, we demonstrate a novel strategy (Disaggregation for Intracellular Signaling in Single Epithelial Cells from Tissue—DISSECT) that preserves native signaling for Cytometry Time-of-Flight (CyTOF) and fluorescent flow cytometry appl...
Source: Molecular Systems Biology - October 30, 2015 Category: Molecular Biology Authors: Simmons, A. J., Banerjee, A., McKinley, E. T., Scurrah, C. R., Herring, C. A., Gewin, L. S., Masuzaki, R., Karp, S. J., Franklin, J. L., Gerdes, M. J., Irish, J. M., Coffey, R. J., Lau, K. S. Tags: Methods & Resources, Signal Transduction Articles Source Type: research
Acetylation dynamics and stoichiometry in Saccharomyces cerevisiae
(Source: Molecular Systems Biology)
Source: Molecular Systems Biology - October 26, 2015 Category: Molecular Biology Authors: Weinert, B. T., Iesmantavicius, V., Moustafa, T., Schölz, C., Wagner, S. A., Magnes, C., Zechner, R., Choudhary, C. Tags: Genome-Scale & Integrative Biology, Post-translational Modifications, Proteolysis & Proteomics Corrigendum Source Type: research
The gut microbiota modulates host amino acid and glutathione metabolism in mice
The gut microbiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gut microbiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtained from conventionally raised (CONV-R) and germ-free (GF) mice using gene expression data and tissue-specific genome-scale metabolic models (GEMs). We created a generic mouse metabolic reaction (MMR) GEM, reconstructed 28 tissue-specific GEMs based on proteomics data, and manually curated GEMs for small intestine, colon, liver, and adipos...
Source: Molecular Systems Biology - October 16, 2015 Category: Molecular Biology Authors: Mardinoglu, A., Shoaie, S., Bergentall, M., Ghaffari, P., Zhang, C., Larsson, E., Bäckhed, F., Nielsen, J. Tags: Genome-Scale & Integrative Biology, Metabolism, Microbiology, Virology & Host Pathogen Interaction Articles Source Type: research
Do genome-scale models need exact solvers or clearer standards?
(Source: Molecular Systems Biology)
Source: Molecular Systems Biology - October 14, 2015 Category: Molecular Biology Authors: Ebrahim, A., Almaas, E., Bauer, E., Bordbar, A., Burgard, A. P., Chang, R. L., Dräger, A., Famili, I., Feist, A. M., Fleming, R. M., Fong, S. S., Hatzimanikatis, V., Herrgard, M. J., Holder, A., Hucka, M., Hyduke, D., Jamshidi, N., Lee, S. Y., Le Tags: Computational Biology, Metabolism, Methods & Resources Correspondence Source Type: research
Reply to "Do genome-scale models need exact solvers or clearer standards?"
(Source: Molecular Systems Biology)
Source: Molecular Systems Biology - October 14, 2015 Category: Molecular Biology Authors: Chindelevitch, L., Trigg, J., Regev, A., Berger, B. Tags: Computational Biology, Metabolism, Methods & Resources Correspondence Source Type: research
Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds
Since deleterious mutations may be rescued by secondary mutations during evolution, compensatory evolution could identify genetic solutions leading to therapeutic targets. Here, we tested this hypothesis and examined whether these solutions would be universal or would need to be adapted to one's genetic and environmental makeups. We performed experimental evolutionary rescue in a yeast disease model for the Wiskott–Aldrich syndrome in two genetic backgrounds and carbon sources. We found that multiple aspects of the evolutionary rescue outcome depend on the genotype, the environment, or a combination thereof. Specific...
Source: Molecular Systems Biology - October 12, 2015 Category: Molecular Biology Authors: Filteau, M., Hamel, V., Pouliot, M.-C., Gagnon-Arsenault, I., Dube, A. K., Landry, C. R. Tags: Chromatin, Epigenetics, Genomics & Functional Genomics Articles Source Type: research
Condition-specific genetic interaction maps reveal crosstalk between the cAMP/PKA and the HOG MAPK pathways in the activation of the general stress response
Cells must quickly respond and efficiently adapt to environmental changes. The yeast Saccharomyces cerevisiae has multiple pathways that respond to specific environmental insults, as well as a generic stress response program. The later is regulated by two transcription factors, Msn2 and Msn4, that integrate information from upstream pathways to produce fast, tunable, and robust response to different environmental changes. To understand this integration, we employed a systematic approach to genetically dissect the contribution of various cellular pathways to Msn2/4 regulation under a range of stress and growth conditions. W...
Source: Molecular Systems Biology - October 7, 2015 Category: Molecular Biology Authors: Gutin, J., Sadeh, A., Rahat, A., Aharoni, A., Friedman, N. Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Signal Transduction, Transcription Articles Source Type: research
A cell-based model system links chromothripsis with hyperploidy
A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed "complex alterations after selection and transformation (CAST)," enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencin...
Source: Molecular Systems Biology - September 28, 2015 Category: Molecular Biology Authors: Mardin, B. R., Drainas, A. P., Waszak, S. M., Weischenfeldt, J., Isokane, M., Stutz, A. M., Raeder, B., Efthymiopoulos, T., Buccitelli, C., Segura-Wang, M., Northcott, P., Pfister, S. M., Lichter, P., Ellenberg, J., Korbel, J. O. Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, DNA Replication, Repair & Recombination, Methods & Resources Articles Source Type: research
