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  • Article
    Orthogonal intercellular signaling for programmed spatial behavior
    Orthogonal intercellular signaling for programmed spatial behavior
    1. Paul K Grant1,2,,
    2. Neil Dalchau2,,
    3. James R Brown1,2,
    4. Fernan Federici1,3,
    5. Timothy J Rudge1,
    6. Boyan Yordanov2,
    7. Om Patange1,
    8. Andrew Phillips2 and
    9. Jim Haseloff*,1
    1. 1Department of Plant Sciences, University of Cambridge, Cambridge, UK
    2. 2Computational Science Laboratory, Microsoft Research, Cambridge, UK
    3. 3Departamento de Genética Molecular y Microbiologia, Facultad de Cs. Biológicas, Universidad Católica de Chile, Santiago, Chile
    1. *Corresponding author. Tel: +44 1223333900; E‐mail: jh295{at}cam.ac.uk
    1. These authors contributed equally to this work

    The use of multiple homoserine lactone quorum‐sensing signals in synthetic circuits has been hampered by crosstalk. Measurement and modeling of the system allows for rational modifications to minimize crosstalk and create programmed spatial behavior.

    Synopsis

    The use of multiple homoserine lactone quorum‐sensing signals in synthetic circuits has been hampered by crosstalk. Measurement and modeling of the system allows for rational modifications to minimize crosstalk and create programmed spatial behavior.

    • Quantitative measurements were used to build and parameterize a cellular model of synthetic signal transduction.

    • Rationally designed changes to promoter sequences combined with model‐informed tuning of receiver protein expression reduce crosstalk to undetectable levels.

    • A novel spatial assay allows measurement of confined bacterial populations in defined geometries.

    • Relay devices demonstrate bidirectional communication resulting in initiation and spatial propagation of a signal.

    • modeling
    • quorum sensing
    • spatial patterning
    • synthetic biology

    Mol Syst Biol. (2016) 12: 849

    • Received September 18, 2015.
    • Revision received November 19, 2015.
    • Accepted November 23, 2015.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Paul K Grant, Neil Dalchau, James R Brown, Fernan Federici, Timothy J Rudge, Boyan Yordanov, Om Patange, Andrew Phillips, Jim Haseloff
  • News & Views
    The interdependence of transcript and protein abundance: new data–new complexities
    The interdependence of transcript and protein abundance: new data–new complexities
    1. Yansheng Liu (liu{at}imsb.biol.ethz.ch)1 and
    2. Ruedi Aebersold (aebersold{at}imsb.biol.ethz.ch)1,2
    1. 1Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
    2. 2Faculty of Science, University of Zurich, Zurich, Switzerland

    The relative contribution of transcriptional and translational regulation in gene expression control has been intensely debated and remains a challenging question. Recent reports have suggested that protein abundance in mammalian cells is primarily controlled at the transcript‐level. In their recent work, Cheng et al (2016) determined the proteomic and transcriptomic changes in cells responding to endoplasmic reticulum (ER) stress. Their analyses indicate that the ER stress response is significantly controlled at both the transcript and protein levels.

    See also: Z Cheng et al (January 2016)

    The relative contribution of transcriptional and translational regulation in gene expression control remains an open question. Vogel and colleagues (Cheng et al, 2016) show that the endoplasmic reticulum stress response is controlled at both the transcript and protein levels.

    Mol Syst Biol. (2016) 12: 856

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Yansheng Liu, Ruedi Aebersold
  • Article
    Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress
    Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress
    1. Zhe Cheng1,,
    2. Guoshou Teo2,3,,
    3. Sabrina Krueger4,
    4. Tara M Rock1,
    5. Hiromi WL Koh2,3,
    6. Hyungwon Choi*,2,3, and
    7. Christine Vogel*,1,
    1. 1Center for Genomics and Systems Biology, New York University, New York, NY, USA
    2. 2Saw Swee Hock School of Public Health, National University Singapore, Singapore
    3. 3National University Health System, Singapore
    4. 4Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany
    1. * Corresponding author. Tel: +65 6601 1448; E‐mail: hyung_won_choi{at}nuhs.edu.sg
      Corresponding author. Tel: +1 212 998 3976; E‐mail: cvogel{at}nyu.edu
    1. These authors contributed equally to this work

    2. These authors contributed equally to this work

    The contribution of mRNA and protein level regulation in the mammalian endoplasmic reticulum stress response is deconvoluted by analyzing time‐series protein and matching mRNA concentrations with a new statistical tool.

    Synopsis

    The contribution of mRNA and protein level regulation in the mammalian endoplasmic reticulum stress response is deconvoluted by analyzing time‐series protein and matching mRNA concentrations with a new statistical tool.

    • Protein and mRNA concentrations are quantified at different time points, generating a high‐confidence dataset of 1,237 genes/mRNAs.

    • A new statistical tool quantifies the contribution of regulatory processes and shows that mRNA and protein level regulation play similarly important roles.

    • mRNA and protein level regulation have different dynamics: mRNA concentrations spike in their change and return to pre‐perturbation levels, while protein concentrations switch in their behavior and reach a new steady‐state.

    • Hypotheses on modes of regulation for several groups of genes are presented.

    • Central Dogma
    • ER stress
    • mammalian proteomics
    • mass spectrometry
    • PECA

    Mol Syst Biol. (2016) 12: 855

    • Received July 4, 2015.
    • Revision received December 4, 2015.
    • Accepted December 8, 2015.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Zhe Cheng, Guoshou Teo, Sabrina Krueger, Tara M Rock, Hiromi WL Koh, Hyungwon Choi, Christine Vogel
  • Article
    Antisense transcription as a tool to tune gene expression
    Antisense transcription as a tool to tune gene expression
    1. Jennifer AN Brophy1 and
    2. Christopher A Voigt*,1
    1. 1Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
    1. *Corresponding author. Tel: +1 617 324 4851; E‐mail: cavoigt{at}gmail.com

    A synthetic system developed in Escherichia coli and a computational model provide mechanistic insights into antisense transcription and show that it is a reliable means of controlling gene expression and tuning regulatory circuits.

    Synopsis

    A synthetic system developed in Escherichia coli and a computational model provide mechanistic insights into antisense transcription and show that it is a reliable means of controlling gene expression and tuning regulatory circuits.

    • A large library of terminator–promoter combinations is used to quantify the role of antisense transcription in regulatory networks.

    • The degree to which antisense promoters repress gene expression is proportional to the strength of the antisense promoter.

    • Antisense RNA and transcriptional interference each contribute equally to the total repression that can be achieved using antisense promoters.

    • A set of unidirectional terminators and constitutive promoters can be combined in a modular manner to implement gene expression control.

    • antisense transcription
    • design automation
    • genetic circuits
    • synthetic biology
    • systems biology

    Mol Syst Biol. (2016) 12: 854

    • Received August 31, 2015.
    • Revision received December 4, 2015.
    • Accepted December 7, 2015.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Jennifer AN Brophy, Christopher A Voigt
  • Report
    Regulation of alternative splicing at the single‐cell level
    Regulation of alternative splicing at the single‐cell level
    1. Lior Faigenbloom1,,
    2. Nimrod D Rubinstein24,
    3. Yoel Kloog1,
    4. Itay Mayrose3,
    5. Tal Pupko*,2 and
    6. Reuven Stein*,1
    1. 1The Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
    2. 2The Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
    3. 3The Department of Molecular Biology and Ecology of Plants, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
    4. 4Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA
    1. * Corresponding author. Tel: +972 6 640 7693; E‐mail: talp{at}tau.ac.il
      Corresponding author. Tel: +972 3 640 8608; E‐mail: reuvens{at}post.tau.ac.il
    1. These authors contributed equally to this work

    Single‐cell quantification of expression levels of alternatively spliced isoforms identifies what governs the precision of cassette exon inclusion levels among single cells in a cell population.

    Synopsis

    Single‐cell quantification of expression levels of alternatively spliced isoforms identifies what governs the precision of cassette exon inclusion levels among single cells in a cell population.

    • While most cassette exons in the human genome are flanked by lowly evolutionarily conserved intronic regions, a small fraction of cassette exons is flanked by highly evolutionarily conserved intronic regions.

    • Evolutionary conservation at flanking intronic regions (FIRs) of cassette exons significantly increases the precision of cassette exon inclusion levels among homogenous single cells derived from human cell lines.

    • Dominant cassette exon inclusion or exclusion levels, as well as high expression levels of the genes harboring them, also contribute to this precision.

    • The precision of inclusion levels of cassette exons, which are involved in human stem cell differentiation, is similarly regulated by these three factors.

    • alternative splicing
    • evolutionary conservation
    • inclusion level
    • single cell
    • splicing regulation

    Mol Syst Biol. (2015) 11: 845

    • Received May 4, 2015.
    • Revision received October 11, 2015.
    • Accepted November 8, 2015.

    This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Lior Faigenbloom, Nimrod D Rubinstein, Yoel Kloog, Itay Mayrose, Tal Pupko, Reuven Stein
  • Commentary
    The BioStudies database
    The BioStudies database
    1. Jo McEntyre (mcentyre{at}ebi.ac.uk)1,
    2. Ugis Sarkans1 and
    3. Alvis Brazma1
    1. 1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL‐EBI), Wellcome Trust Genome Campus, Hinxton Cambridge, UK

    The BioStudies database is a new EMBL‐EBI resource that holds descriptions of biological studies, links to supporting data in other databases, and archives data files that do not fit in existing public structured archives.

    Mol Syst Biol. (2015) 11: 847

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Jo McEntyre, Ugis Sarkans, Alvis Brazma
  • Commentary
    The evolution of standards and data management practices in systems biology
    The evolution of standards and data management practices in systems biology
    1. Natalie J Stanford*,1,2,
    2. Katherine Wolstencroft3,
    3. Martin Golebiewski4,
    4. Renate Kania4,
    5. Nick Juty5,
    6. Christopher Tomlinson6,
    7. Stuart Owen2,
    8. Sarah Butcher6,
    9. Henning Hermjakob5,
    10. Nicolas Le Novère7,
    11. Wolfgang Mueller4,
    12. Jacky Snoep8,9 and
    13. Carole Goble2
    1. 1Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK
    2. 2School of Computer Science, University of Manchester, Manchester, UK
    3. 3Leiden Institute of Advanced Computer Science, Leiden Institute of Advanced Computer Science, Leiden University, Leiden, The Netherlands
    4. 4Heidelberg Institute for Theoretical Studies, Heidelberg, Germany
    5. 5European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL‐EBI), Cambridge, UK
    6. 6Department of Surgery and Cancer, Imperial College London, London, UK
    7. 7Babraham Institute, Cambridge, UK
    8. 8Department of Biochemistry, University of Stellenbosch, Matieland, South Africa
    9. 9School of Chemical Engineering & Analytical Science, The University of Manchester, Manchester, UK
    1. *Corresponding author. Tel: +44 161 275 0145; E‐mail: natalie.stanford{at}manchester.ac.uk

    A recent community survey conducted by Infrastructure for Systems Biology Europe (ISBE) informs requirements for developing an efficient infrastructure for systems biology standards, data and model management.

    Mol Syst Biol. (2015) 11: 851

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Natalie J Stanford, Katherine Wolstencroft, Martin Golebiewski, Renate Kania, Nick Juty, Christopher Tomlinson, Stuart Owen, Sarah Butcher, Henning Hermjakob, Nicolas Le Novère, Wolfgang Mueller, Jacky Snoep, Carole Goble