---
_id: '723'
abstract:
- lang: eng
  text: Escaping local optima is one of the major obstacles to function optimisation.
    Using the metaphor of a fitness landscape, local optima correspond to hills separated
    by fitness valleys that have to be overcome. We define a class of fitness valleys
    of tunable difficulty by considering their length, representing the Hamming path
    between the two optima and their depth, the drop in fitness. For this function
    class we present a runtime comparison between stochastic search algorithms using
    different search strategies. The (1+1) EA is a simple and well-studied evolutionary
    algorithm that has to jump across the valley to a point of higher fitness because
    it does not accept worsening moves (elitism). In contrast, the Metropolis algorithm
    and the Strong Selection Weak Mutation (SSWM) algorithm, a famous process in population
    genetics, are both able to cross the fitness valley by accepting worsening moves.
    We show that the runtime of the (1+1) EA depends critically on the length of the
    valley while the runtimes of the non-elitist algorithms depend crucially on the
    depth of the valley. Moreover, we show that both SSWM and Metropolis can also
    efficiently optimise a rugged function consisting of consecutive valleys.
article_processing_charge: No
author:
- first_name: Pietro
  full_name: Oliveto, Pietro
  last_name: Oliveto
- first_name: Tiago
  full_name: Paixao, Tiago
  id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
  last_name: Paixao
  orcid: 0000-0003-2361-3953
- first_name: Jorge
  full_name: Pérez Heredia, Jorge
  last_name: Pérez Heredia
- first_name: Dirk
  full_name: Sudholt, Dirk
  last_name: Sudholt
- first_name: Barbora
  full_name: Trubenova, Barbora
  id: 42302D54-F248-11E8-B48F-1D18A9856A87
  last_name: Trubenova
  orcid: 0000-0002-6873-2967
citation:
  ama: Oliveto P, Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. How to escape
    local optima in black box optimisation when non elitism outperforms elitism. <i>Algorithmica</i>.
    2018;80(5):1604-1633. doi:<a href="https://doi.org/10.1007/s00453-017-0369-2">10.1007/s00453-017-0369-2</a>
  apa: Oliveto, P., Paixao, T., Pérez Heredia, J., Sudholt, D., &#38; Trubenova, B.
    (2018). How to escape local optima in black box optimisation when non elitism
    outperforms elitism. <i>Algorithmica</i>. Springer. <a href="https://doi.org/10.1007/s00453-017-0369-2">https://doi.org/10.1007/s00453-017-0369-2</a>
  chicago: Oliveto, Pietro, Tiago Paixao, Jorge Pérez Heredia, Dirk Sudholt, and Barbora
    Trubenova. “How to Escape Local Optima in Black Box Optimisation When Non Elitism
    Outperforms Elitism.” <i>Algorithmica</i>. Springer, 2018. <a href="https://doi.org/10.1007/s00453-017-0369-2">https://doi.org/10.1007/s00453-017-0369-2</a>.
  ieee: P. Oliveto, T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “How
    to escape local optima in black box optimisation when non elitism outperforms
    elitism,” <i>Algorithmica</i>, vol. 80, no. 5. Springer, pp. 1604–1633, 2018.
  ista: Oliveto P, Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. 2018. How to
    escape local optima in black box optimisation when non elitism outperforms elitism.
    Algorithmica. 80(5), 1604–1633.
  mla: Oliveto, Pietro, et al. “How to Escape Local Optima in Black Box Optimisation
    When Non Elitism Outperforms Elitism.” <i>Algorithmica</i>, vol. 80, no. 5, Springer,
    2018, pp. 1604–33, doi:<a href="https://doi.org/10.1007/s00453-017-0369-2">10.1007/s00453-017-0369-2</a>.
  short: P. Oliveto, T. Paixao, J. Pérez Heredia, D. Sudholt, B. Trubenova, Algorithmica
    80 (2018) 1604–1633.
date_created: 2018-12-11T11:48:09Z
date_published: 2018-05-01T00:00:00Z
date_updated: 2025-04-15T08:22:22Z
day: '01'
ddc:
- '576'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1007/s00453-017-0369-2
ec_funded: 1
external_id:
  isi:
  - '000428239300010'
file:
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file_date_updated: 2020-07-14T12:47:54Z
fulldoi: https://doi.org/10.1007/s00453-017-0369-2
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intvolume: '        80'
isi: 1
issue: '5'
language:
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month: '05'
oa: 1
oa_version: Published Version
page: 1604 - 1633
project:
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  call_identifier: FP7
  grant_number: '618091'
  name: Speed of Adaptation in Population Genetics and Evolutionary Computation
publication: Algorithmica
publication_status: published
publisher: Springer
publist_id: '6957'
pubrep_id: '1014'
quality_controlled: '1'
scopus_import: '1'
status: public
title: How to escape local optima in black box optimisation when non elitism outperforms
  elitism
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 80
year: '2018'
...
---
OA_place: publisher
_id: '26'
abstract:
- lang: eng
  text: Expression of genes is a fundamental molecular phenotype that is subject to
    evolution by different types of mutations. Both the rate and the effect of mutations
    may depend on the DNA sequence context of a particular gene or a particular promoter
    sequence. In this thesis I investigate the nature of this dependence using simple
    genetic systems in Escherichia coli. With these systems I explore the evolution
    of constitutive gene expression from random starting sequences at different loci
    on the chromosome and at different locations in sequence space. First, I dissect
    chromosomal neighborhood effects that underlie locus-dependent differences in
    the potential of a gene under selection to become more highly expressed. Next,
    I find that the effects of point mutations in promoter sequences are dependent
    on sequence context, and that an existing energy matrix model performs poorly
    in predicting relative expression of unrelated sequences. Finally, I show that
    a substantial fraction of random sequences contain functional promoters and I
    present an extended thermodynamic model that predicts promoter strength in full
    sequence space. Taken together, these results provide new insights and guides
    on how to integrate information on sequence context to improve our qualitative
    and quantitative understanding of bacterial gene expression, with implications
    for rapid evolution of drug resistance, de novo evolution of genes, and horizontal
    gene transfer.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Magdalena
  full_name: Steinrück, Magdalena
  id: 2C023F40-F248-11E8-B48F-1D18A9856A87
  last_name: Steinrück
  orcid: 0000-0003-1229-9719
citation:
  ama: Steinrück M. The influence of sequence context on the evolution of bacterial
    gene expression. 2018. doi:<a href="https://doi.org/10.15479/AT:ISTA:th1059">10.15479/AT:ISTA:th1059</a>
  apa: Steinrück, M. (2018). <i>The influence of sequence context on the evolution
    of bacterial gene expression</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/AT:ISTA:th1059">https://doi.org/10.15479/AT:ISTA:th1059</a>
  chicago: Steinrück, Magdalena. “The Influence of Sequence Context on the Evolution
    of Bacterial Gene Expression.” Institute of Science and Technology Austria, 2018.
    <a href="https://doi.org/10.15479/AT:ISTA:th1059">https://doi.org/10.15479/AT:ISTA:th1059</a>.
  ieee: M. Steinrück, “The influence of sequence context on the evolution of bacterial
    gene expression,” Institute of Science and Technology Austria, 2018.
  ista: Steinrück M. 2018. The influence of sequence context on the evolution of bacterial
    gene expression. Institute of Science and Technology Austria.
  mla: Steinrück, Magdalena. <i>The Influence of Sequence Context on the Evolution
    of Bacterial Gene Expression</i>. Institute of Science and Technology Austria,
    2018, doi:<a href="https://doi.org/10.15479/AT:ISTA:th1059">10.15479/AT:ISTA:th1059</a>.
  short: M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial
    Gene Expression, Institute of Science and Technology Austria, 2018.
corr_author: '1'
date_created: 2018-12-11T11:44:14Z
date_published: 2018-10-30T00:00:00Z
date_updated: 2026-04-08T14:15:35Z
day: '30'
ddc:
- '576'
- '579'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:th1059
file:
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fulldoi: https://doi.org/10.15479/AT:ISTA:th1059
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '109'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8029'
pubrep_id: '1059'
related_material:
  record:
  - id: '704'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
title: The influence of sequence context on the evolution of bacterial gene expression
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2018'
...
---
_id: '67'
abstract:
- lang: eng
  text: 'Gene regulatory networks evolve through rewiring of individual components—that
    is, through changes in regulatory connections. However, the mechanistic basis
    of regulatory rewiring is poorly understood. Using a canonical gene regulatory
    system, we quantify the properties of transcription factors that determine the
    evolutionary potential for rewiring of regulatory connections: robustness, tunability
    and evolvability. In vivo repression measurements of two repressors at mutated
    operator sites reveal their contrasting evolutionary potential: while robustness
    and evolvability were positively correlated, both were in trade-off with tunability.
    Epistatic interactions between adjacent operators alleviated this trade-off. A
    thermodynamic model explains how the differences in robustness, tunability and
    evolvability arise from biophysical characteristics of repressor–DNA binding.
    The model also uncovers that the energy matrix, which describes how mutations
    affect repressor–DNA binding, encodes crucial information about the evolutionary
    potential of a repressor. The biophysical determinants of evolutionary potential
    for regulatory rewiring constitute a mechanistic framework for understanding network
    evolution.'
article_processing_charge: No
article_type: original
author:
- first_name: Claudia
  full_name: Igler, Claudia
  id: 46613666-F248-11E8-B48F-1D18A9856A87
  last_name: Igler
  orcid: 0000-0001-7777-546X
- first_name: Mato
  full_name: Lagator, Mato
  id: 345D25EC-F248-11E8-B48F-1D18A9856A87
  last_name: Lagator
- first_name: Gasper
  full_name: Tkacik, Gasper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkacik
  orcid: 0000-0002-6699-1455
- first_name: Jonathan P
  full_name: Bollback, Jonathan P
  id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
  last_name: Bollback
  orcid: 0000-0002-4624-4612
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
citation:
  ama: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential
    of transcription factors for gene regulatory rewiring. <i>Nature Ecology and Evolution</i>.
    2018;2(10):1633-1643. doi:<a href="https://doi.org/10.1038/s41559-018-0651-y">10.1038/s41559-018-0651-y</a>
  apa: Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., &#38; Guet, C. C. (2018).
    Evolutionary potential of transcription factors for gene regulatory rewiring.
    <i>Nature Ecology and Evolution</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/s41559-018-0651-y">https://doi.org/10.1038/s41559-018-0651-y</a>
  chicago: Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin
    C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.”
    <i>Nature Ecology and Evolution</i>. Nature Publishing Group, 2018. <a href="https://doi.org/10.1038/s41559-018-0651-y">https://doi.org/10.1038/s41559-018-0651-y</a>.
  ieee: C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary
    potential of transcription factors for gene regulatory rewiring,” <i>Nature Ecology
    and Evolution</i>, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018.
  ista: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential
    of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution.
    2(10), 1633–1643.
  mla: Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for
    Gene Regulatory Rewiring.” <i>Nature Ecology and Evolution</i>, vol. 2, no. 10,
    Nature Publishing Group, 2018, pp. 1633–43, doi:<a href="https://doi.org/10.1038/s41559-018-0651-y">10.1038/s41559-018-0651-y</a>.
  short: C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology
    and Evolution 2 (2018) 1633–1643.
date_created: 2018-12-11T11:44:27Z
date_published: 2018-09-10T00:00:00Z
date_updated: 2026-11-02T23:30:29Z
day: '10'
ddc:
- '570'
department:
- _id: CaGu
- _id: GaTk
- _id: JoBo
doi: 10.1038/s41559-018-0651-y
ec_funded: 1
external_id:
  isi:
  - '000447947600021'
file:
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  date_created: 2020-05-14T11:28:52Z
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  file_id: '7830'
  file_name: 2018_NatureEcology_Igler.pdf
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file_date_updated: 2020-07-14T12:47:37Z
fulldoi: https://doi.org/10.1038/s41559-018-0651-y
has_accepted_license: '1'
intvolume: '         2'
isi: 1
issue: '10'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Submitted Version
page: 1633 - 1643
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 2578D616-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '648440'
  name: Selective Barriers to Horizontal Gene Transfer
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
  grant_number: '24573'
  name: Design principles underlying genetic switch architecture
publication: Nature Ecology and Evolution
publication_status: published
publisher: Nature Publishing Group
publist_id: '7987'
quality_controlled: '1'
related_material:
  record:
  - id: '5585'
    relation: popular_science
    status: public
  - id: '6371'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Evolutionary potential of transcription factors for gene regulatory rewiring
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 2
year: '2018'
...
---
_id: '5585'
abstract:
- lang: eng
  text: Mean repression values and standard error of the mean are given for all operator
    mutant libraries.
article_processing_charge: No
author:
- first_name: Claudia
  full_name: Igler, Claudia
  id: 46613666-F248-11E8-B48F-1D18A9856A87
  last_name: Igler
  orcid: 0000-0001-7777-546X
- first_name: Mato
  full_name: Lagator, Mato
  id: 345D25EC-F248-11E8-B48F-1D18A9856A87
  last_name: Lagator
- first_name: Gasper
  full_name: Tkacik, Gasper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkacik
  orcid: 0000-0002-6699-1455
- first_name: Jonathan P
  full_name: Bollback, Jonathan P
  id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
  last_name: Bollback
  orcid: 0000-0002-4624-4612
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
citation:
  ama: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Data for the paper Evolutionary
    potential of transcription factors for gene regulatory rewiring. 2018. doi:<a
    href="https://doi.org/10.15479/AT:ISTA:108">10.15479/AT:ISTA:108</a>
  apa: Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., &#38; Guet, C. C. (2018).
    Data for the paper Evolutionary potential of transcription factors for gene regulatory
    rewiring. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:108">https://doi.org/10.15479/AT:ISTA:108</a>
  chicago: Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin
    C Guet. “Data for the Paper Evolutionary Potential of Transcription Factors for
    Gene Regulatory Rewiring.” Institute of Science and Technology Austria, 2018.
    <a href="https://doi.org/10.15479/AT:ISTA:108">https://doi.org/10.15479/AT:ISTA:108</a>.
  ieee: C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Data for
    the paper Evolutionary potential of transcription factors for gene regulatory
    rewiring.” Institute of Science and Technology Austria, 2018.
  ista: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Data for the paper
    Evolutionary potential of transcription factors for gene regulatory rewiring,
    Institute of Science and Technology Austria, <a href="https://doi.org/10.15479/AT:ISTA:108">10.15479/AT:ISTA:108</a>.
  mla: Igler, Claudia, et al. <i>Data for the Paper Evolutionary Potential of Transcription
    Factors for Gene Regulatory Rewiring</i>. Institute of Science and Technology
    Austria, 2018, doi:<a href="https://doi.org/10.15479/AT:ISTA:108">10.15479/AT:ISTA:108</a>.
  short: C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, (2018).
datarep_id: '108'
date_created: 2018-12-12T12:31:40Z
date_published: 2018-07-20T00:00:00Z
date_updated: 2026-11-02T23:30:29Z
day: '20'
ddc:
- '576'
department:
- _id: CaGu
- _id: GaTk
doi: 10.15479/AT:ISTA:108
ec_funded: 1
file:
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fulldoi: https://doi.org/10.15479/AT:ISTA:108
has_accepted_license: '1'
license: https://creativecommons.org/publicdomain/zero/1.0/
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 2578D616-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '648440'
  name: Selective Barriers to Horizontal Gene Transfer
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
  grant_number: '24573'
  name: Design principles underlying genetic switch architecture
publisher: Institute of Science and Technology Austria
related_material:
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  - id: '67'
    relation: research_paper
    status: public
  - id: '6371'
    relation: research_paper
    status: public
status: public
title: Data for the paper Evolutionary potential of transcription factors for gene
  regulatory rewiring
tmp:
  image: /images/cc_0.png
  legal_code_url: https://creativecommons.org/publicdomain/zero/1.0/legalcode
  name: Creative Commons Public Domain Dedication (CC0 1.0)
  short: CC0 (1.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2018'
...
---
_id: '1084'
abstract:
- lang: eng
  text: 'BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis
    controlling the response to antimicrobial peptides. In the presence of extracellular
    bacitracin and nisin, respectively, the two response regulators (RRs) bind their
    target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target
    gene expression and ultimately antibiotic resistance. Despite high sequence similarity
    between the RRs BceR and PsdR and their known binding sites, no cross-regulation
    has been observed between them. We therefore investigated the specificity determinants
    of PbceA and PpsdA that ensure the insulation of these two paralogous pathways
    at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the
    regulatory regions within these two promoters contain three important elements:
    in addition to the known (main) binding site, we identified a linker region and
    a secondary binding site that are crucial for functionality. Initial binding to
    the high-affinity, low-specificity main binding site is a prerequisite for the
    subsequent highly specific binding of a second RR dimer to the low-affinity secondary
    binding site. In addition to this hierarchical cooperative binding, discrimination
    requires a competition of the two RRs for their respective binding site mediated
    by only slight differences in binding affinities.'
article_processing_charge: No
author:
- first_name: Chong
  full_name: Fang, Chong
  last_name: Fang
- first_name: Anna A
  full_name: Nagy-Staron, Anna A
  id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
  last_name: Nagy-Staron
  orcid: 0000-0002-1391-8377
- first_name: Martin
  full_name: Grafe, Martin
  last_name: Grafe
- first_name: Ralf
  full_name: Heermann, Ralf
  last_name: Heermann
- first_name: Kirsten
  full_name: Jung, Kirsten
  last_name: Jung
- first_name: Susanne
  full_name: Gebhard, Susanne
  last_name: Gebhard
- first_name: Thorsten
  full_name: Mascher, Thorsten
  last_name: Mascher
citation:
  ama: Fang C, Nagy-Staron AA, Grafe M, et al. Insulation and wiring specificity of
    BceR like response regulators and their target promoters in Bacillus subtilis.
    <i>Molecular Microbiology</i>. 2017;104(1):16-31. doi:<a href="https://doi.org/10.1111/mmi.13597">10.1111/mmi.13597</a>
  apa: Fang, C., Nagy-Staron, A. A., Grafe, M., Heermann, R., Jung, K., Gebhard, S.,
    &#38; Mascher, T. (2017). Insulation and wiring specificity of BceR like response
    regulators and their target promoters in Bacillus subtilis. <i>Molecular Microbiology</i>.
    Wiley-Blackwell. <a href="https://doi.org/10.1111/mmi.13597">https://doi.org/10.1111/mmi.13597</a>
  chicago: Fang, Chong, Anna A Nagy-Staron, Martin Grafe, Ralf Heermann, Kirsten Jung,
    Susanne Gebhard, and Thorsten Mascher. “Insulation and Wiring Specificity of BceR
    like Response Regulators and Their Target Promoters in Bacillus Subtilis.” <i>Molecular
    Microbiology</i>. Wiley-Blackwell, 2017. <a href="https://doi.org/10.1111/mmi.13597">https://doi.org/10.1111/mmi.13597</a>.
  ieee: C. Fang <i>et al.</i>, “Insulation and wiring specificity of BceR like response
    regulators and their target promoters in Bacillus subtilis,” <i>Molecular Microbiology</i>,
    vol. 104, no. 1. Wiley-Blackwell, pp. 16–31, 2017.
  ista: Fang C, Nagy-Staron AA, Grafe M, Heermann R, Jung K, Gebhard S, Mascher T.
    2017. Insulation and wiring specificity of BceR like response regulators and their
    target promoters in Bacillus subtilis. Molecular Microbiology. 104(1), 16–31.
  mla: Fang, Chong, et al. “Insulation and Wiring Specificity of BceR like Response
    Regulators and Their Target Promoters in Bacillus Subtilis.” <i>Molecular Microbiology</i>,
    vol. 104, no. 1, Wiley-Blackwell, 2017, pp. 16–31, doi:<a href="https://doi.org/10.1111/mmi.13597">10.1111/mmi.13597</a>.
  short: C. Fang, A.A. Nagy-Staron, M. Grafe, R. Heermann, K. Jung, S. Gebhard, T.
    Mascher, Molecular Microbiology 104 (2017) 16–31.
date_created: 2018-12-11T11:50:03Z
date_published: 2017-04-01T00:00:00Z
date_updated: 2026-04-16T09:56:09Z
day: '01'
department:
- _id: CaGu
doi: 10.1111/mmi.13597
external_id:
  isi:
  - '000398059200002'
fulldoi: https://doi.org/10.1111/mmi.13597
intvolume: '       104'
isi: 1
issue: '1'
language:
- iso: eng
month: '04'
oa_version: None
page: 16 - 31
publication: Molecular Microbiology
publication_identifier:
  issn:
  - ' 0950-382X'
publication_status: published
publisher: Wiley-Blackwell
publist_id: '6294'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Insulation and wiring specificity of BceR like response regulators and their
  target promoters in Bacillus subtilis
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 104
year: '2017'
...
---
_id: '1336'
abstract:
- lang: eng
  text: Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired
    by natural evolution. In recent years the field of evolutionary computation has
    developed a rigorous analytical theory to analyse the runtimes of EAs on many
    illustrative problems. Here we apply this theory to a simple model of natural
    evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the
    time between occurrences of new mutations is much longer than the time it takes
    for a mutated genotype to take over the population. In this situation, the population
    only contains copies of one genotype and evolution can be modelled as a stochastic
    process evolving one genotype by means of mutation and selection between the resident
    and the mutated genotype. The probability of accepting the mutated genotype then
    depends on the change in fitness. We study this process, SSWM, from an algorithmic
    perspective, quantifying its expected optimisation time for various parameters
    and investigating differences to a similar evolutionary algorithm, the well-known
    (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at
    crossing fitness valleys and study an example where SSWM outperforms the (1+1)
    EA by taking advantage of information on the fitness gradient.
article_processing_charge: No
author:
- first_name: Tiago
  full_name: Paixao, Tiago
  id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
  last_name: Paixao
  orcid: 0000-0003-2361-3953
- first_name: Jorge
  full_name: Pérez Heredia, Jorge
  last_name: Pérez Heredia
- first_name: Dirk
  full_name: Sudholt, Dirk
  last_name: Sudholt
- first_name: Barbora
  full_name: Trubenova, Barbora
  id: 42302D54-F248-11E8-B48F-1D18A9856A87
  last_name: Trubenova
  orcid: 0000-0002-6873-2967
citation:
  ama: Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. Towards a runtime comparison
    of natural and artificial evolution. <i>Algorithmica</i>. 2017;78(2):681-713.
    doi:<a href="https://doi.org/10.1007/s00453-016-0212-1">10.1007/s00453-016-0212-1</a>
  apa: Paixao, T., Pérez Heredia, J., Sudholt, D., &#38; Trubenova, B. (2017). Towards
    a runtime comparison of natural and artificial evolution. <i>Algorithmica</i>.
    Springer. <a href="https://doi.org/10.1007/s00453-016-0212-1">https://doi.org/10.1007/s00453-016-0212-1</a>
  chicago: Paixao, Tiago, Jorge Pérez Heredia, Dirk Sudholt, and Barbora Trubenova.
    “Towards a Runtime Comparison of Natural and Artificial Evolution.” <i>Algorithmica</i>.
    Springer, 2017. <a href="https://doi.org/10.1007/s00453-016-0212-1">https://doi.org/10.1007/s00453-016-0212-1</a>.
  ieee: T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “Towards a runtime
    comparison of natural and artificial evolution,” <i>Algorithmica</i>, vol. 78,
    no. 2. Springer, pp. 681–713, 2017.
  ista: Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. 2017. Towards a runtime
    comparison of natural and artificial evolution. Algorithmica. 78(2), 681–713.
  mla: Paixao, Tiago, et al. “Towards a Runtime Comparison of Natural and Artificial
    Evolution.” <i>Algorithmica</i>, vol. 78, no. 2, Springer, 2017, pp. 681–713,
    doi:<a href="https://doi.org/10.1007/s00453-016-0212-1">10.1007/s00453-016-0212-1</a>.
  short: T. Paixao, J. Pérez Heredia, D. Sudholt, B. Trubenova, Algorithmica 78 (2017)
    681–713.
date_created: 2018-12-11T11:51:27Z
date_published: 2017-06-01T00:00:00Z
date_updated: 2026-04-16T09:55:33Z
day: '01'
ddc:
- '576'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1007/s00453-016-0212-1
ec_funded: 1
external_id:
  isi:
  - '000400379500013'
file:
- access_level: open_access
  checksum: 7873f665a0c598ac747c908f34cb14b9
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:10:19Z
  date_updated: 2020-07-14T12:44:44Z
  file_id: '4805'
  file_name: IST-2016-658-v1+1_s00453-016-0212-1.pdf
  file_size: 710206
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file_date_updated: 2020-07-14T12:44:44Z
fulldoi: https://doi.org/10.1007/s00453-016-0212-1
has_accepted_license: '1'
intvolume: '        78'
isi: 1
issue: '2'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 681 - 713
project:
- _id: 25B1EC9E-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618091'
  name: Speed of Adaptation in Population Genetics and Evolutionary Computation
publication: Algorithmica
publication_identifier:
  issn:
  - 0178-4617
publication_status: published
publisher: Springer
publist_id: '5931'
pubrep_id: '658'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Towards a runtime comparison of natural and artificial evolution
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 78
year: '2017'
...
---
_id: '1351'
abstract:
- lang: eng
  text: The behaviour of gene regulatory networks (GRNs) is typically analysed using
    simulation-based statistical testing-like methods. In this paper, we demonstrate
    that we can replace this approach by a formal verification-like method that gives
    higher assurance and scalability. We focus on Wagner’s weighted GRN model with
    varying weights, which is used in evolutionary biology. In the model, weight parameters
    represent the gene interaction strength that may change due to genetic mutations.
    For a property of interest, we synthesise the constraints over the parameter space
    that represent the set of GRNs satisfying the property. We experimentally show
    that our parameter synthesis procedure computes the mutational robustness of GRNs—an
    important problem of interest in evolutionary biology—more efficiently than the
    classical simulation method. We specify the property in linear temporal logic.
    We employ symbolic bounded model checking and SMT solving to compute the space
    of GRNs that satisfy the property, which amounts to synthesizing a set of linear
    constraints on the weights.
article_processing_charge: No
author:
- first_name: Mirco
  full_name: Giacobbe, Mirco
  id: 3444EA5E-F248-11E8-B48F-1D18A9856A87
  last_name: Giacobbe
  orcid: 0000-0001-8180-0904
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
- first_name: Ashutosh
  full_name: Gupta, Ashutosh
  id: 335E5684-F248-11E8-B48F-1D18A9856A87
  last_name: Gupta
- first_name: Thomas A
  full_name: Henzinger, Thomas A
  id: 40876CD8-F248-11E8-B48F-1D18A9856A87
  last_name: Henzinger
  orcid: 0000−0002−2985−7724
- first_name: Tiago
  full_name: Paixao, Tiago
  id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
  last_name: Paixao
  orcid: 0000-0003-2361-3953
- first_name: Tatjana
  full_name: Petrov, Tatjana
  id: 3D5811FC-F248-11E8-B48F-1D18A9856A87
  last_name: Petrov
  orcid: 0000-0002-9041-0905
citation:
  ama: Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. Model checking
    the evolution of gene regulatory networks. <i>Acta Informatica</i>. 2017;54(8):765-787.
    doi:<a href="https://doi.org/10.1007/s00236-016-0278-x">10.1007/s00236-016-0278-x</a>
  apa: Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., &#38; Petrov,
    T. (2017). Model checking the evolution of gene regulatory networks. <i>Acta Informatica</i>.
    Springer. <a href="https://doi.org/10.1007/s00236-016-0278-x">https://doi.org/10.1007/s00236-016-0278-x</a>
  chicago: Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago
    Paixao, and Tatjana Petrov. “Model Checking the Evolution of Gene Regulatory Networks.”
    <i>Acta Informatica</i>. Springer, 2017. <a href="https://doi.org/10.1007/s00236-016-0278-x">https://doi.org/10.1007/s00236-016-0278-x</a>.
  ieee: M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov,
    “Model checking the evolution of gene regulatory networks,” <i>Acta Informatica</i>,
    vol. 54, no. 8. Springer, pp. 765–787, 2017.
  ista: Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. 2017. Model
    checking the evolution of gene regulatory networks. Acta Informatica. 54(8), 765–787.
  mla: Giacobbe, Mirco, et al. “Model Checking the Evolution of Gene Regulatory Networks.”
    <i>Acta Informatica</i>, vol. 54, no. 8, Springer, 2017, pp. 765–87, doi:<a href="https://doi.org/10.1007/s00236-016-0278-x">10.1007/s00236-016-0278-x</a>.
  short: M. Giacobbe, C.C. Guet, A. Gupta, T.A. Henzinger, T. Paixao, T. Petrov, Acta
    Informatica 54 (2017) 765–787.
corr_author: '1'
date_created: 2018-12-11T11:51:32Z
date_published: 2017-12-01T00:00:00Z
date_updated: 2025-07-10T11:50:42Z
day: '01'
ddc:
- '006'
- '576'
department:
- _id: ToHe
- _id: CaGu
- _id: NiBa
doi: 10.1007/s00236-016-0278-x
ec_funded: 1
external_id:
  isi:
  - '000414343200003'
file:
- access_level: open_access
  checksum: 4e661d9135d7f8c342e8e258dee76f3e
  content_type: application/pdf
  creator: dernst
  date_created: 2019-01-17T15:57:29Z
  date_updated: 2020-07-14T12:44:46Z
  file_id: '5841'
  file_name: 2017_ActaInformatica_Giacobbe.pdf
  file_size: 755241
  relation: main_file
file_date_updated: 2020-07-14T12:44:46Z
fulldoi: https://doi.org/10.1007/s00236-016-0278-x
has_accepted_license: '1'
intvolume: '        54'
isi: 1
issue: '8'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 765 - 787
project:
- _id: 25EE3708-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '267989'
  name: Quantitative Reactive Modeling
- _id: 25832EC2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: S 11407_N23
  name: Rigorous Systems Engineering
- _id: 25F42A32-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z211
  name: Formal methods for the design and analysis of complex systems
- _id: 25B1EC9E-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618091'
  name: Speed of Adaptation in Population Genetics and Evolutionary Computation
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 25B07788-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '250152'
  name: Limits to selection in biology and in evolutionary computation
publication: Acta Informatica
publication_identifier:
  issn:
  - 0001-5903
publication_status: published
publisher: Springer
publist_id: '5898'
pubrep_id: '649'
quality_controlled: '1'
related_material:
  record:
  - id: '1835'
    relation: earlier_version
    status: public
scopus_import: '1'
status: public
title: Model checking the evolution of gene regulatory networks
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 54
year: '2017'
...
---
_id: '538'
abstract:
- lang: ger
  text: 'Optogenetik und Photopharmakologie ermöglichen präzise räumliche und zeitliche
    Kontrolle von Proteinwechselwirkung und -funktion in Zellen und Tieren. Optogenetische
    Methoden, die auf grünes Licht ansprechen und zum Trennen von Proteinkomplexen
    geeignet sind, sind nichtweitläufig verfügbar, würden jedoch mehrfarbige Experimente
    zur Beantwortung von biologischen Fragestellungen ermöglichen. Hier demonstrieren
    wir die Verwendung von Cobalamin(Vitamin B12)-bindenden Domänen von bakteriellen
    CarH-Transkriptionsfaktoren zur Grünlicht-induzierten Dissoziation von Rezeptoren.
    Fusioniert mit dem Fibroblasten-W achstumsfaktor-Rezeptor 1 führten diese im Dunkeln
    in kultivierten Zellen zu Signalaktivität durch Oligomerisierung, welche durch
    Beleuchten umgehend aufgehoben wurde. In Zebrafischembryonen, die einen derartigen
    Rezeptor exprimieren, ermöglichte grünes Licht die Kontrolle über abnormale Signalaktivität
    während der Embryonalentwicklung. '
author:
- first_name: Stephanie
  full_name: Kainrath, Stephanie
  id: 32CFBA64-F248-11E8-B48F-1D18A9856A87
  last_name: Kainrath
- first_name: Manuela
  full_name: Stadler, Manuela
  last_name: Stadler
- first_name: Eva
  full_name: Gschaider-Reichhart, Eva
  id: 3FEE232A-F248-11E8-B48F-1D18A9856A87
  last_name: Gschaider-Reichhart
  orcid: 0000-0002-7218-7738
- first_name: Martin
  full_name: Distel, Martin
  last_name: Distel
- first_name: Harald L
  full_name: Janovjak, Harald L
  id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
  last_name: Janovjak
  orcid: 0000-0002-8023-9315
citation:
  ama: Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. Grünlicht-induzierte
    Rezeptorinaktivierung durch Cobalamin-bindende Domänen. <i>Angewandte Chemie</i>.
    2017;129(16):4679-4682. doi:<a href="https://doi.org/10.1002/ange.201611998">10.1002/ange.201611998</a>
  apa: Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., &#38; Janovjak,
    H. L. (2017). Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende
    Domänen. <i>Angewandte Chemie</i>. Wiley. <a href="https://doi.org/10.1002/ange.201611998">https://doi.org/10.1002/ange.201611998</a>
  chicago: Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel,
    and Harald L Janovjak. “Grünlicht-Induzierte Rezeptorinaktivierung Durch Cobalamin-Bindende
    Domänen.” <i>Angewandte Chemie</i>. Wiley, 2017. <a href="https://doi.org/10.1002/ange.201611998">https://doi.org/10.1002/ange.201611998</a>.
  ieee: S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak,
    “Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen,”
    <i>Angewandte Chemie</i>, vol. 129, no. 16. Wiley, pp. 4679–4682, 2017.
  ista: Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017.
    Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte
    Chemie. 129(16), 4679–4682.
  mla: Kainrath, Stephanie, et al. “Grünlicht-Induzierte Rezeptorinaktivierung Durch
    Cobalamin-Bindende Domänen.” <i>Angewandte Chemie</i>, vol. 129, no. 16, Wiley,
    2017, pp. 4679–82, doi:<a href="https://doi.org/10.1002/ange.201611998">10.1002/ange.201611998</a>.
  short: S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak,
    Angewandte Chemie 129 (2017) 4679–4682.
corr_author: '1'
date_created: 2018-12-11T11:47:02Z
date_published: 2017-05-20T00:00:00Z
date_updated: 2024-10-09T20:58:07Z
day: '20'
ddc:
- '571'
department:
- _id: CaGu
- _id: HaJa
doi: 10.1002/ange.201611998
ec_funded: 1
file:
- access_level: open_access
  checksum: d66fee867e7cdbfa3fe276c2fb0778bb
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:13:24Z
  date_updated: 2020-07-14T12:46:39Z
  file_id: '5007'
  file_name: IST-2018-932-v1+1_Kainrath_et_al-2017-Angewandte_Chemie.pdf
  file_size: 1668557
  relation: main_file
file_date_updated: 2020-07-14T12:46:39Z
fulldoi: https://doi.org/10.1002/ange.201611998
has_accepted_license: '1'
intvolume: '       129'
issue: '16'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: 4679 - 4682
project:
- _id: 25548C20-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '303564'
  name: Microbial Ion Channels for Synthetic Neurobiology
- _id: 255A6082-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
publication: Angewandte Chemie
publication_status: published
publisher: Wiley
publist_id: '7279'
pubrep_id: '932'
quality_controlled: '1'
status: public
title: Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 129
year: '2017'
...
---
_id: '541'
abstract:
- lang: eng
  text: 'While we have good understanding of bacterial metabolism at the population
    level, we know little about the metabolic behavior of individual cells: do single
    cells in clonal populations sometimes specialize on different metabolic pathways?
    Such metabolic specialization could be driven by stochastic gene expression and
    could provide individual cells with growth benefits of specialization. We measured
    the degree of phenotypic specialization in two parallel metabolic pathways, the
    assimilation of glucose and arabinose. We grew Escherichia coli in chemostats,
    and used isotope-labeled sugars in combination with nanometer-scale secondary
    ion mass spectrometry and mathematical modeling to quantify sugar assimilation
    at the single-cell level. We found large variation in metabolic activities between
    single cells, both in absolute assimilation and in the degree to which individual
    cells specialize in the assimilation of different sugars. Analysis of transcriptional
    reporters indicated that this variation was at least partially based on cell-to-cell
    variation in gene expression. Metabolic differences between cells in clonal populations
    could potentially reduce metabolic incompatibilities between different pathways,
    and increase the rate at which parallel reactions can be performed.'
article_number: e1007122
article_processing_charge: No
author:
- first_name: Nela
  full_name: Nikolic, Nela
  id: 42D9CABC-F248-11E8-B48F-1D18A9856A87
  last_name: Nikolic
  orcid: 0000-0001-9068-6090
- first_name: Frank
  full_name: Schreiber, Frank
  last_name: Schreiber
- first_name: Alma
  full_name: Dal Co, Alma
  last_name: Dal Co
- first_name: Daniel
  full_name: Kiviet, Daniel
  last_name: Kiviet
- first_name: Tobias
  full_name: Bergmiller, Tobias
  id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
  last_name: Bergmiller
  orcid: 0000-0001-5396-4346
- first_name: Sten
  full_name: Littmann, Sten
  last_name: Littmann
- first_name: Marcel
  full_name: Kuypers, Marcel
  last_name: Kuypers
- first_name: Martin
  full_name: Ackermann, Martin
  last_name: Ackermann
citation:
  ama: Nikolic N, Schreiber F, Dal Co A, et al. Cell-to-cell variation and specialization
    in sugar metabolism in clonal bacterial populations. <i>PLoS Genetics</i>. 2017;13(12).
    doi:<a href="https://doi.org/10.1371/journal.pgen.1007122">10.1371/journal.pgen.1007122</a>
  apa: Nikolic, N., Schreiber, F., Dal Co, A., Kiviet, D., Bergmiller, T., Littmann,
    S., … Ackermann, M. (2017). Cell-to-cell variation and specialization in sugar
    metabolism in clonal bacterial populations. <i>PLoS Genetics</i>. Public Library
    of Science. <a href="https://doi.org/10.1371/journal.pgen.1007122">https://doi.org/10.1371/journal.pgen.1007122</a>
  chicago: Nikolic, Nela, Frank Schreiber, Alma Dal Co, Daniel Kiviet, Tobias Bergmiller,
    Sten Littmann, Marcel Kuypers, and Martin Ackermann. “Cell-to-Cell Variation and
    Specialization in Sugar Metabolism in Clonal Bacterial Populations.” <i>PLoS Genetics</i>.
    Public Library of Science, 2017. <a href="https://doi.org/10.1371/journal.pgen.1007122">https://doi.org/10.1371/journal.pgen.1007122</a>.
  ieee: N. Nikolic <i>et al.</i>, “Cell-to-cell variation and specialization in sugar
    metabolism in clonal bacterial populations,” <i>PLoS Genetics</i>, vol. 13, no.
    12. Public Library of Science, 2017.
  ista: Nikolic N, Schreiber F, Dal Co A, Kiviet D, Bergmiller T, Littmann S, Kuypers
    M, Ackermann M. 2017. Cell-to-cell variation and specialization in sugar metabolism
    in clonal bacterial populations. PLoS Genetics. 13(12), e1007122.
  mla: Nikolic, Nela, et al. “Cell-to-Cell Variation and Specialization in Sugar Metabolism
    in Clonal Bacterial Populations.” <i>PLoS Genetics</i>, vol. 13, no. 12, e1007122,
    Public Library of Science, 2017, doi:<a href="https://doi.org/10.1371/journal.pgen.1007122">10.1371/journal.pgen.1007122</a>.
  short: N. Nikolic, F. Schreiber, A. Dal Co, D. Kiviet, T. Bergmiller, S. Littmann,
    M. Kuypers, M. Ackermann, PLoS Genetics 13 (2017).
corr_author: '1'
date_created: 2018-12-11T11:47:04Z
date_published: 2017-12-18T00:00:00Z
date_updated: 2025-09-18T09:42:09Z
day: '18'
ddc:
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department:
- _id: CaGu
doi: 10.1371/journal.pgen.1007122
ec_funded: 1
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  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
publication: PLoS Genetics
publication_identifier:
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publication_status: published
publisher: Public Library of Science
publist_id: '7275'
pubrep_id: '959'
quality_controlled: '1'
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status: public
title: Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial
  populations
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abstract:
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  text: "This repository contains the data collected for the manuscript \"Biased partitioning
    of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity\".\r\nThe
    data is compressed into a single archive. Within the archive, different folders
    correspond to figures of the main text and the SI of the related publication.\r\nData
    is saved as plain text, with each folder containing a separate readme file describing
    the format. Typically, the data is from fluorescence microscopy measurements of
    single cells growing in a microfluidic \"mother machine\" device, and consists
    of relevant values (primarily arbitrary unit or normalized fluorescence measurements,
    and division times / growth rates) after raw microscopy images have been processed,
    segmented, and their features extracted, as described in the methods section of
    the related publication."
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  id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
  last_name: Bergmiller
  orcid: 0000-0001-5396-4346
- first_name: Anna M
  full_name: Andersson, Anna M
  id: 2B8A40DA-F248-11E8-B48F-1D18A9856A87
  last_name: Andersson
  orcid: 0000-0003-2912-6769
- first_name: Kathrin
  full_name: Tomasek, Kathrin
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  last_name: Tomasek
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- first_name: Enrique
  full_name: Balleza, Enrique
  last_name: Balleza
- first_name: Daniel
  full_name: Kiviet, Daniel
  last_name: Kiviet
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
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  last_name: Tkacik
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  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
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citation:
  ama: Bergmiller T, Andersson AM, Tomasek K, et al. Biased partitioning of the multi-drug
    efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity. 2017. doi:<a
    href="https://doi.org/10.15479/AT:ISTA:53">10.15479/AT:ISTA:53</a>
  apa: Bergmiller, T., Andersson, A. M., Tomasek, K., Balleza, E., Kiviet, D., Hauschild,
    R., … Guet, C. C. (2017). Biased partitioning of the multi-drug efflux pump AcrAB-TolC
    underlies long-lived phenotypic heterogeneity. Institute of Science and Technology
    Austria. <a href="https://doi.org/10.15479/AT:ISTA:53">https://doi.org/10.15479/AT:ISTA:53</a>
  chicago: Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza,
    Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning
    of the Multi-Drug Efflux Pump AcrAB-TolC Underlies Long-Lived Phenotypic Heterogeneity.”
    Institute of Science and Technology Austria, 2017. <a href="https://doi.org/10.15479/AT:ISTA:53">https://doi.org/10.15479/AT:ISTA:53</a>.
  ieee: T. Bergmiller <i>et al.</i>, “Biased partitioning of the multi-drug efflux
    pump AcrAB-TolC underlies long-lived phenotypic heterogeneity.” Institute of Science
    and Technology Austria, 2017.
  ista: Bergmiller T, Andersson AM, Tomasek K, Balleza E, Kiviet D, Hauschild R, Tkačik
    G, Guet CC. 2017. Biased partitioning of the multi-drug efflux pump AcrAB-TolC
    underlies long-lived phenotypic heterogeneity, Institute of Science and Technology
    Austria, <a href="https://doi.org/10.15479/AT:ISTA:53">10.15479/AT:ISTA:53</a>.
  mla: Bergmiller, Tobias, et al. <i>Biased Partitioning of the Multi-Drug Efflux
    Pump AcrAB-TolC Underlies Long-Lived Phenotypic Heterogeneity</i>. Institute of
    Science and Technology Austria, 2017, doi:<a href="https://doi.org/10.15479/AT:ISTA:53">10.15479/AT:ISTA:53</a>.
  short: T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild,
    G. Tkačik, C.C. Guet, (2017).
datarep_id: '53'
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date_updated: 2025-09-11T07:05:03Z
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ddc:
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department:
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- _id: GaTk
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doi: 10.15479/AT:ISTA:53
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fulldoi: https://doi.org/10.15479/AT:ISTA:53
has_accepted_license: '1'
keyword:
- single cell microscopy
- mother machine microfluidic device
- AcrAB-TolC pump
- multi-drug efflux
- Escherichia coli
month: '03'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
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title: Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived
  phenotypic heterogeneity
tmp:
  image: /images/cc_0.png
  legal_code_url: https://creativecommons.org/publicdomain/zero/1.0/legalcode
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type: research_data
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...
---
_id: '5564'
abstract:
- lang: eng
  text: Compressed Fastq files with whole-genome sequencing data of IS-wt strain D
    and clones from four evolved populations (A11, C08, C10, D08). Information on
    this data collection is available in the Methods Section of the primary publication.
article_processing_charge: No
author:
- first_name: Magdalena
  full_name: Steinrück, Magdalena
  id: 2C023F40-F248-11E8-B48F-1D18A9856A87
  last_name: Steinrück
  orcid: 0000-0003-1229-9719
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
citation:
  ama: Steinrück M, Guet CC. Fastq files for “Complex chromosomal neighborhood effects
    determine the adaptive potential of a gene under selection.” 2017. doi:<a href="https://doi.org/10.15479/AT:ISTA:65">10.15479/AT:ISTA:65</a>
  apa: Steinrück, M., &#38; Guet, C. C. (2017). Fastq files for “Complex chromosomal
    neighborhood effects determine the adaptive potential of a gene under selection.”
    Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:65">https://doi.org/10.15479/AT:ISTA:65</a>
  chicago: Steinrück, Magdalena, and Calin C Guet. “Fastq Files for ‘Complex Chromosomal
    Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.’”
    Institute of Science and Technology Austria, 2017. <a href="https://doi.org/10.15479/AT:ISTA:65">https://doi.org/10.15479/AT:ISTA:65</a>.
  ieee: M. Steinrück and C. C. Guet, “Fastq files for ‘Complex chromosomal neighborhood
    effects determine the adaptive potential of a gene under selection.’” Institute
    of Science and Technology Austria, 2017.
  ista: Steinrück M, Guet CC. 2017. Fastq files for ‘Complex chromosomal neighborhood
    effects determine the adaptive potential of a gene under selection’, Institute
    of Science and Technology Austria, <a href="https://doi.org/10.15479/AT:ISTA:65">10.15479/AT:ISTA:65</a>.
  mla: Steinrück, Magdalena, and Calin C. Guet. <i>Fastq Files for “Complex Chromosomal
    Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.”</i>
    Institute of Science and Technology Austria, 2017, doi:<a href="https://doi.org/10.15479/AT:ISTA:65">10.15479/AT:ISTA:65</a>.
  short: M. Steinrück, C.C. Guet, (2017).
datarep_id: '65'
date_created: 2018-12-12T12:31:33Z
date_published: 2017-04-11T00:00:00Z
date_updated: 2025-09-10T11:06:52Z
day: '11'
ddc:
- '576'
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:65
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month: '04'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
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  - id: '704'
    relation: research_paper
    status: public
status: public
title: Fastq files for "Complex chromosomal neighborhood effects determine the adaptive
  potential of a gene under selection"
tmp:
  image: /images/cc_0.png
  legal_code_url: https://creativecommons.org/publicdomain/zero/1.0/legalcode
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...
---
_id: '561'
abstract:
- lang: eng
  text: Restriction–modification systems are widespread genetic elements that protect
    bacteria from bacteriophage infections by recognizing and cleaving heterologous
    DNA at short, well-defined sequences called restriction sites. Bioinformatic evidence
    shows that restriction sites are significantly underrepresented in bacteriophage
    genomes, presumably because bacteriophages with fewer restriction sites are more
    likely to escape cleavage by restriction–modification systems. However, how mutations
    in restriction sites affect the likelihood of bacteriophage escape is unknown.
    Using the bacteriophage l and the restriction–modification system EcoRI, we show
    that while mutation effects at different restriction sites are unequal, they are
    independent. As a result, the probability of bacteriophage escape increases with
    each mutated restriction site. Our results experimentally support the role of
    restriction site avoidance as a response to selection imposed by restriction–modification
    systems and offer an insight into the events underlying the process of bacteriophage
    escape.
acknowledgement: This work was funded by an HFSP Young Investigators' grant RGY0079/2011
  (C.C.G.). M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science
  at the Institute of Science and Technology Austria.
article_number: '20170646'
article_processing_charge: No
article_type: original
author:
- first_name: Maros
  full_name: Pleska, Maros
  id: 4569785E-F248-11E8-B48F-1D18A9856A87
  last_name: Pleska
  orcid: 0000-0001-7460-7479
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
citation:
  ama: Pleska M, Guet CC. Effects of mutations in phage restriction sites during escape
    from restriction–modification. <i>Biology Letters</i>. 2017;13(12). doi:<a href="https://doi.org/10.1098/rsbl.2017.0646">10.1098/rsbl.2017.0646</a>
  apa: Pleska, M., &#38; Guet, C. C. (2017). Effects of mutations in phage restriction
    sites during escape from restriction–modification. <i>Biology Letters</i>. The
    Royal Society. <a href="https://doi.org/10.1098/rsbl.2017.0646">https://doi.org/10.1098/rsbl.2017.0646</a>
  chicago: Pleska, Maros, and Calin C Guet. “Effects of Mutations in Phage Restriction
    Sites during Escape from Restriction–Modification.” <i>Biology Letters</i>. The
    Royal Society, 2017. <a href="https://doi.org/10.1098/rsbl.2017.0646">https://doi.org/10.1098/rsbl.2017.0646</a>.
  ieee: M. Pleska and C. C. Guet, “Effects of mutations in phage restriction sites
    during escape from restriction–modification,” <i>Biology Letters</i>, vol. 13,
    no. 12. The Royal Society, 2017.
  ista: Pleska M, Guet CC. 2017. Effects of mutations in phage restriction sites during
    escape from restriction–modification. Biology Letters. 13(12), 20170646.
  mla: Pleska, Maros, and Calin C. Guet. “Effects of Mutations in Phage Restriction
    Sites during Escape from Restriction–Modification.” <i>Biology Letters</i>, vol.
    13, no. 12, 20170646, The Royal Society, 2017, doi:<a href="https://doi.org/10.1098/rsbl.2017.0646">10.1098/rsbl.2017.0646</a>.
  short: M. Pleska, C.C. Guet, Biology Letters 13 (2017).
corr_author: '1'
date_created: 2018-12-11T11:47:11Z
date_published: 2017-12-01T00:00:00Z
date_updated: 2026-06-18T18:54:20Z
day: '01'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1098/rsbl.2017.0646
external_id:
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month: '12'
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project:
- _id: 251BCBEC-B435-11E9-9278-68D0E5697425
  grant_number: RGY0079/2011
  name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification
    Systems
- _id: 251D65D8-B435-11E9-9278-68D0E5697425
  grant_number: '24210'
  name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems
    at the Single-Cell Level
publication: Biology Letters
publication_identifier:
  issn:
  - 1744-9561
publication_status: published
publisher: The Royal Society
publist_id: '7253'
quality_controlled: '1'
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status: public
title: Effects of mutations in phage restriction sites during escape from restriction–modification
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 13
year: '2017'
...
---
_id: '570'
abstract:
- lang: eng
  text: 'Most phenotypes are determined by molecular systems composed of specifically
    interacting molecules. However, unlike for individual components, little is known
    about the distributions of mutational effects of molecular systems as a whole.
    We ask how the distribution of mutational effects of a transcriptional regulatory
    system differs from the distributions of its components, by first independently,
    and then simultaneously, mutating a transcription factor and the associated promoter
    it represses. We find that the system distribution exhibits increased phenotypic
    variation compared to individual component distributions - an effect arising from
    intermolecular epistasis between the transcription factor and its DNA-binding
    site. In large part, this epistasis can be qualitatively attributed to the structure
    of the transcriptional regulatory system and could therefore be a common feature
    in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the
    constraints of individual components, thereby increasing phenotypic variation
    that selection could act on and facilitating adaptive evolution. '
article_number: e28921
article_processing_charge: No
author:
- first_name: Mato
  full_name: Lagator, Mato
  id: 345D25EC-F248-11E8-B48F-1D18A9856A87
  last_name: Lagator
- first_name: Srdjan
  full_name: Sarikas, Srdjan
  id: 35F0286E-F248-11E8-B48F-1D18A9856A87
  last_name: Sarikas
- first_name: Hande
  full_name: Acar, Hande
  id: 2DDF136A-F248-11E8-B48F-1D18A9856A87
  last_name: Acar
  orcid: 0000-0003-1986-9753
- first_name: Jonathan P
  full_name: Bollback, Jonathan P
  id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
  last_name: Bollback
  orcid: 0000-0002-4624-4612
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
citation:
  ama: Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure
    determines patterns of intermolecular epistasis. <i>eLife</i>. 2017;6. doi:<a
    href="https://doi.org/10.7554/eLife.28921">10.7554/eLife.28921</a>
  apa: Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., &#38; Guet, C. C. (2017).
    Regulatory network structure determines patterns of intermolecular epistasis.
    <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.28921">https://doi.org/10.7554/eLife.28921</a>
  chicago: Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin
    C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.”
    <i>ELife</i>. eLife Sciences Publications, 2017. <a href="https://doi.org/10.7554/eLife.28921">https://doi.org/10.7554/eLife.28921</a>.
  ieee: M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory
    network structure determines patterns of intermolecular epistasis,” <i>eLife</i>,
    vol. 6. eLife Sciences Publications, 2017.
  ista: Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network
    structure determines patterns of intermolecular epistasis. eLife. 6, e28921.
  mla: Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of
    Intermolecular Epistasis.” <i>ELife</i>, vol. 6, e28921, eLife Sciences Publications,
    2017, doi:<a href="https://doi.org/10.7554/eLife.28921">10.7554/eLife.28921</a>.
  short: M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017).
corr_author: '1'
date_created: 2018-12-11T11:47:14Z
date_published: 2017-11-13T00:00:00Z
date_updated: 2025-09-11T07:40:30Z
day: '13'
ddc:
- '576'
department:
- _id: CaGu
- _id: JoBo
- _id: NiBa
doi: 10.7554/eLife.28921
ec_funded: 1
external_id:
  isi:
  - '000425868200001'
file:
- access_level: open_access
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  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:14:42Z
  date_updated: 2020-07-14T12:47:10Z
  file_id: '5096'
  file_name: IST-2017-918-v1+1_elife-28921-figures-v3.pdf
  file_size: 8453470
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  content_type: application/pdf
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file_date_updated: 2020-07-14T12:47:10Z
fulldoi: https://doi.org/10.7554/eLife.28921
has_accepted_license: '1'
intvolume: '         6'
isi: 1
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 2578D616-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '648440'
  name: Selective Barriers to Horizontal Gene Transfer
publication: eLife
publication_identifier:
  issn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
publist_id: '7244'
pubrep_id: '918'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Regulatory network structure determines patterns of intermolecular epistasis
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 6
year: '2017'
...
---
_id: '613'
abstract:
- lang: eng
  text: 'Bacteria in groups vary individually, and interact with other bacteria and
    the environment to produce population-level patterns of gene expression. Investigating
    such behavior in detail requires measuring and controlling populations at the
    single-cell level alongside precisely specified interactions and environmental
    characteristics. Here we present an automated, programmable platform that combines
    image-based gene expression and growth measurements with on-line optogenetic expression
    control for hundreds of individual Escherichia coli cells over days, in a dynamically
    adjustable environment. This integrated platform broadly enables experiments that
    bridge individual and population behaviors. We demonstrate: (i) population structuring
    by independent closed-loop control of gene expression in many individual cells,
    (ii) cell-cell variation control during antibiotic perturbation, (iii) hybrid
    bio-digital circuits in single cells, and freely specifiable digital communication
    between individual bacteria. These examples showcase the potential for real-time
    integration of theoretical models with measurement and control of many individual
    cells to investigate and engineer microbial population behavior.'
acknowledgement: We are grateful to M. Lang, H. Janovjak, M. Khammash, A. Milias-Argeitis,
  M. Rullan, G. Batt, A. Bosma-Moody, Aryan, S. Leibler, and members of the Guet and
  Tkačik groups for helpful discussion, comments, and suggestions. We thank A. Moglich,
  T. Mathes, J. Tabor, and S. Schmidl for kind gifts of strains, and R. Hauschild,
  B. Knep, M. Lang, T. Asenov, E. Papusheva, T. Menner, T. Adletzberger, and J. Merrin
  for technical assistance. The research leading to these results has received funding
  from the People Programme (Marie Curie Actions) of the European Union’s Seventh
  Framework Programme (FP7/2007–2013) under REA grant agreement no. [291734]. (to
  R.C. and J.R.), Austrian Science Fund grant FWF P28844 (to G.T.), and internal IST
  Austria Interdisciplinary Project Support. J.R. acknowledges support from the Agence
  Nationale de la Recherche (ANR) under Grant Nos. ANR-16-CE33-0018 (MEMIP), ANR-16-CE12-0025
  (COGEX) and ANR-10-BINF-06-01 (ICEBERG).
article_number: '1535'
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Remy P
  full_name: Chait, Remy P
  id: 3464AE84-F248-11E8-B48F-1D18A9856A87
  last_name: Chait
  orcid: 0000-0003-0876-3187
- first_name: Jakob
  full_name: Ruess, Jakob
  id: 4A245D00-F248-11E8-B48F-1D18A9856A87
  last_name: Ruess
  orcid: 0000-0003-1615-3282
- first_name: Tobias
  full_name: Bergmiller, Tobias
  id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
  last_name: Bergmiller
  orcid: 0000-0001-5396-4346
- first_name: Gasper
  full_name: Tkacik, Gasper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkacik
  orcid: 0000-0002-6699-1455
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
citation:
  ama: Chait RP, Ruess J, Bergmiller T, Tkačik G, Guet CC. Shaping bacterial population
    behavior through computer interfaced control of individual cells. <i>Nature Communications</i>.
    2017;8(1). doi:<a href="https://doi.org/10.1038/s41467-017-01683-1">10.1038/s41467-017-01683-1</a>
  apa: Chait, R. P., Ruess, J., Bergmiller, T., Tkačik, G., &#38; Guet, C. C. (2017).
    Shaping bacterial population behavior through computer interfaced control of individual
    cells. <i>Nature Communications</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/s41467-017-01683-1">https://doi.org/10.1038/s41467-017-01683-1</a>
  chicago: Chait, Remy P, Jakob Ruess, Tobias Bergmiller, Gašper Tkačik, and Calin
    C Guet. “Shaping Bacterial Population Behavior through Computer Interfaced Control
    of Individual Cells.” <i>Nature Communications</i>. Nature Publishing Group, 2017.
    <a href="https://doi.org/10.1038/s41467-017-01683-1">https://doi.org/10.1038/s41467-017-01683-1</a>.
  ieee: R. P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, and C. C. Guet, “Shaping
    bacterial population behavior through computer interfaced control of individual
    cells,” <i>Nature Communications</i>, vol. 8, no. 1. Nature Publishing Group,
    2017.
  ista: Chait RP, Ruess J, Bergmiller T, Tkačik G, Guet CC. 2017. Shaping bacterial
    population behavior through computer interfaced control of individual cells. Nature
    Communications. 8(1), 1535.
  mla: Chait, Remy P., et al. “Shaping Bacterial Population Behavior through Computer
    Interfaced Control of Individual Cells.” <i>Nature Communications</i>, vol. 8,
    no. 1, 1535, Nature Publishing Group, 2017, doi:<a href="https://doi.org/10.1038/s41467-017-01683-1">10.1038/s41467-017-01683-1</a>.
  short: R.P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, C.C. Guet, Nature Communications
    8 (2017).
corr_author: '1'
date_created: 2018-12-11T11:47:30Z
date_published: 2017-12-01T00:00:00Z
date_updated: 2025-09-11T07:34:12Z
day: '01'
ddc:
- '576'
- '579'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1038/s41467-017-01683-1
ec_funded: 1
external_id:
  isi:
  - '000415323000008'
file:
- access_level: open_access
  checksum: 44bb5d0229926c23a9955d9fe0f9723f
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:16:05Z
  date_updated: 2020-07-14T12:47:20Z
  file_id: '5190'
  file_name: IST-2017-911-v1+1_s41467-017-01683-1.pdf
  file_size: 1951699
  relation: main_file
file_date_updated: 2020-07-14T12:47:20Z
fulldoi: https://doi.org/10.1038/s41467-017-01683-1
has_accepted_license: '1'
intvolume: '         8'
isi: 1
issue: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 254E9036-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P28844-B27
  name: Biophysics of information processing in gene regulation
publication: Nature Communications
publication_identifier:
  issn:
  - 2041-1723
publication_status: published
publisher: Nature Publishing Group
publist_id: '7191'
pubrep_id: '911'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Shaping bacterial population behavior through computer interfaced control of
  individual cells
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 8
year: '2017'
...
---
_id: '624'
abstract:
- lang: eng
  text: Bacteria adapt to adverse environmental conditions by altering gene expression
    patterns. Recently, a novel stress adaptation mechanism has been described that
    allows Escherichia coli to alter gene expression at the post-transcriptional level.
    The key player in this regulatory pathway is the endoribonuclease MazF, the toxin
    component of the toxin-antitoxin module mazEF that is triggered by various stressful
    conditions. In general, MazF degrades the majority of transcripts by cleaving
    at ACA sites, which results in the retardation of bacterial growth. Furthermore,
    MazF can process a small subset of mRNAs and render them leaderless by removing
    their ribosome binding site. MazF concomitantly modifies ribosomes, making them
    selective for the translation of leaderless mRNAs. In this study, we employed
    fluorescent reporter-systems to investigate mazEF expression during stressful
    conditions, and to infer consequences of the mRNA processing mediated by MazF
    on gene expression at the single-cell level. Our results suggest that mazEF transcription
    is maintained at low levels in single cells encountering adverse conditions, such
    as antibiotic stress or amino acid starvation. Moreover, using the grcA mRNA as
    a model for MazF-mediated mRNA processing, we found that MazF activation promotes
    heterogeneity in the grcA reporter expression, resulting in a subpopulation of
    cells with increased levels of GrcA reporter protein.
acknowledgement: 'Austrian Science Fund (FWF): M1697, P22249; Swiss National Science
  Foundation (SNF): 145706; European Commission;FWF Special Research Program: RNA-REG
  F43'
article_number: '3830'
article_processing_charge: No
author:
- first_name: Nela
  full_name: Nikolic, Nela
  id: 42D9CABC-F248-11E8-B48F-1D18A9856A87
  last_name: Nikolic
  orcid: 0000-0001-9068-6090
- first_name: Zrinka
  full_name: Didara, Zrinka
  last_name: Didara
- first_name: Isabella
  full_name: Moll, Isabella
  last_name: Moll
citation:
  ama: Nikolic N, Didara Z, Moll I. MazF activation promotes translational heterogeneity
    of the grcA mRNA in Escherichia coli populations. <i>PeerJ</i>. 2017;2017(9).
    doi:<a href="https://doi.org/10.7717/peerj.3830">10.7717/peerj.3830</a>
  apa: Nikolic, N., Didara, Z., &#38; Moll, I. (2017). MazF activation promotes translational
    heterogeneity of the grcA mRNA in Escherichia coli populations. <i>PeerJ</i>.
    PeerJ. <a href="https://doi.org/10.7717/peerj.3830">https://doi.org/10.7717/peerj.3830</a>
  chicago: Nikolic, Nela, Zrinka Didara, and Isabella Moll. “MazF Activation Promotes
    Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.”
    <i>PeerJ</i>. PeerJ, 2017. <a href="https://doi.org/10.7717/peerj.3830">https://doi.org/10.7717/peerj.3830</a>.
  ieee: N. Nikolic, Z. Didara, and I. Moll, “MazF activation promotes translational
    heterogeneity of the grcA mRNA in Escherichia coli populations,” <i>PeerJ</i>,
    vol. 2017, no. 9. PeerJ, 2017.
  ista: Nikolic N, Didara Z, Moll I. 2017. MazF activation promotes translational
    heterogeneity of the grcA mRNA in Escherichia coli populations. PeerJ. 2017(9),
    3830.
  mla: Nikolic, Nela, et al. “MazF Activation Promotes Translational Heterogeneity
    of the GrcA MRNA in Escherichia Coli Populations.” <i>PeerJ</i>, vol. 2017, no.
    9, 3830, PeerJ, 2017, doi:<a href="https://doi.org/10.7717/peerj.3830">10.7717/peerj.3830</a>.
  short: N. Nikolic, Z. Didara, I. Moll, PeerJ 2017 (2017).
corr_author: '1'
date_created: 2018-12-11T11:47:33Z
date_published: 2017-09-21T00:00:00Z
date_updated: 2025-09-11T07:30:06Z
day: '21'
ddc:
- '579'
department:
- _id: CaGu
doi: 10.7717/peerj.3830
external_id:
  isi:
  - '000411665900002'
file:
- access_level: open_access
  checksum: 3d79ae6b6eabc90b0eaaed82ff3493b0
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:11:51Z
  date_updated: 2020-07-14T12:47:24Z
  file_id: '4908'
  file_name: IST-2017-909-v1+1_peerj-3830.pdf
  file_size: 682064
  relation: main_file
file_date_updated: 2020-07-14T12:47:24Z
fulldoi: https://doi.org/10.7717/peerj.3830
has_accepted_license: '1'
intvolume: '      2017'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: PeerJ
publication_identifier:
  issn:
  - 2167-8359
publication_status: published
publisher: PeerJ
publist_id: '7172'
pubrep_id: '909'
quality_controlled: '1'
scopus_import: '1'
status: public
title: MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia
  coli populations
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 2017
year: '2017'
...
---
OA_place: publisher
_id: '202'
abstract:
- lang: eng
  text: 'Restriction-modification (RM) represents the simplest and possibly the most
    widespread mechanism of self/non-self discrimination in nature. In order to provide
    bacteria with immunity against bacteriophages and other parasitic genetic elements,
    RM systems rely on a balance between two enzymes: the restriction enzyme, which
    cleaves non-self DNA at specific restriction sites, and the modification enzyme,
    which tags the host’s DNA as self and thus protects it from cleavage. In this
    thesis, I use population and single-cell level experiments in combination with
    mathematical modeling to study different aspects of the interplay between RM systems,
    bacteria and bacteriophages. First, I analyze how mutations in phage restriction
    sites affect the probability of phage escape – an inherently stochastic process,
    during which phages accidently get modified instead of restricted. Next, I use
    single-cell experiments to show that RM systems can, with a low probability, attack
    the genome of their bacterial host and that this primitive form of autoimmunity
    leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally,
    I investigate the nature of interactions between bacteria, RM systems and temperate
    bacteriophages to find that, as a consequence of phage escape and its impact on
    population dynamics, RM systems can promote acquisition of symbiotic bacteriophages,
    rather than limit it. The results presented here uncover new fundamental biological
    properties of RM systems and highlight their importance in the ecology and evolution
    of bacteria, bacteriophages and their interactions.'
acknowledgement: "During my PhD studies, I received help from many people, all of
  which unfortunately cannot be listed here. I thank them deeply and hope that I never
  made them regret their kindness.\r\nI would like to express my deepest gratitude
  to Călin Guet, who went far beyond his responsibilities as an advisor and was to
  me also a great mentor and a friend. Călin never questioned my potential or lacked
  compassion and I cannot thank him enough for cultivating in me an independent scientist.
  I was amazed by his ability to recognize the most fascinating scientific problems
  in objects of study that others would find mundane. I hope I adopted at least a
  fraction of this ability.\r\nI will be forever grateful to Bruce Levin for all his
  support and especially for giving me the best possible example of how one can practice
  excellent science with humor and style. Working with Bruce was a true privilege.\r\nI
  thank Jonathan Bollback and Gašper Tkačik for serving in my PhD committee and the
  Austrian Academy of Science for funding my PhD research via the DOC fellowship.\r\nI
  thank all our lab members: Tobias Bergmiller for his guidance, especially in the
  first years of my research, and for being a good friend throughout; Remy Chait for
  staying in the lab at unreasonable hours and for the good laughs at bad jokes we
  shared; Anna Staron for supportively listening to my whines whenever I had to run
  a gel; Magdalena Steinrück for her pioneering work in the lab; Kathrin Tomasek for
  keeping the entropic forces in check and for her FACS virtuosity; Isabella Tomanek
  for always being nice to me, no matter how much bench space I took from her.\r\nI
  thank all my collaborators: Reiko Okura and Yuichi Wakamoto for performing and analyzing
  the microfluidic experiments; Long Qian and Edo Kussell for their bioinformatics
  analysis; Dominik Refardt for the λ kan phage; Moritz for his help with the mathematical
  modeling. I thank Fabienne Jesse for her tireless editorial work on all our manuscripts.\r\nFinally,
  I would like to thank my family and especially my wife Edita, who sacrificed a lot
  so that I can pursue my goals and dreams.\r\n"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Maros
  full_name: Pleska, Maros
  id: 4569785E-F248-11E8-B48F-1D18A9856A87
  last_name: Pleska
  orcid: 0000-0001-7460-7479
citation:
  ama: Pleska M. Biology of restriction-modification systems at the single-cell and
    population level. 2017. doi:<a href="https://doi.org/10.15479/AT:ISTA:th_916">10.15479/AT:ISTA:th_916</a>
  apa: Pleska, M. (2017). <i>Biology of restriction-modification systems at the single-cell
    and population level</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:th_916">https://doi.org/10.15479/AT:ISTA:th_916</a>
  chicago: Pleska, Maros. “Biology of Restriction-Modification Systems at the Single-Cell
    and Population Level.” Institute of Science and Technology Austria, 2017. <a href="https://doi.org/10.15479/AT:ISTA:th_916">https://doi.org/10.15479/AT:ISTA:th_916</a>.
  ieee: M. Pleska, “Biology of restriction-modification systems at the single-cell
    and population level,” Institute of Science and Technology Austria, 2017.
  ista: Pleska M. 2017. Biology of restriction-modification systems at the single-cell
    and population level. Institute of Science and Technology Austria.
  mla: Pleska, Maros. <i>Biology of Restriction-Modification Systems at the Single-Cell
    and Population Level</i>. Institute of Science and Technology Austria, 2017, doi:<a
    href="https://doi.org/10.15479/AT:ISTA:th_916">10.15479/AT:ISTA:th_916</a>.
  short: M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell
    and Population Level, Institute of Science and Technology Austria, 2017.
corr_author: '1'
date_created: 2018-12-11T11:45:10Z
date_published: 2017-10-01T00:00:00Z
date_updated: 2026-06-18T18:54:19Z
day: '01'
ddc:
- '576'
- '579'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:th_916
file:
- access_level: open_access
  checksum: 33cfb59674e91f82e3738396d3fb3776
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  file_id: '4710'
  file_name: IST-2018-916-v1+3_2017_Pleska_Maros_Thesis.pdf
  file_size: 18569590
  relation: main_file
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  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: dernst
  date_created: 2019-04-05T08:33:14Z
  date_updated: 2020-07-14T12:45:24Z
  file_id: '6204'
  file_name: 2017_Pleska_Maros_Thesis.docx
  file_size: 2801649
  relation: source_file
file_date_updated: 2020-07-14T12:45:24Z
fulldoi: https://doi.org/10.15479/AT:ISTA:th_916
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '126'
project:
- _id: 251D65D8-B435-11E9-9278-68D0E5697425
  grant_number: '24210'
  name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems
    at the Single-Cell Level
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '7711'
pubrep_id: '916'
related_material:
  record:
  - id: '457'
    relation: part_of_dissertation
    status: public
  - id: '1243'
    relation: part_of_dissertation
    status: public
  - id: '561'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
title: Biology of restriction-modification systems at the single-cell and population
  level
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2017'
...
---
_id: '1007'
abstract:
- lang: eng
  text: 'A nonlinear system possesses an invariance with respect to a set of transformations
    if its output dynamics remain invariant when transforming the input, and adjusting
    the initial condition accordingly. Most research has focused on invariances with
    respect to time-independent pointwise transformations like translational-invariance
    (u(t) -&gt; u(t) + p, p in R) or scale-invariance (u(t) -&gt; pu(t), p in R&gt;0).
    In this article, we introduce the concept of s0-invariances with respect to continuous
    input transformations exponentially growing/decaying over time. We show that s0-invariant
    systems not only encompass linear time-invariant (LTI) systems with transfer functions
    having an irreducible zero at s0 in R, but also that the input/output relationship
    of nonlinear s0-invariant systems possesses properties well known from their linear
    counterparts. Furthermore, we extend the concept of s0-invariances to second-
    and higher-order s0-invariances, corresponding to invariances with respect to
    transformations of the time-derivatives of the input, and encompassing LTI systems
    with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant
    systems realize – under mild conditions – nth-order nonlinear differential operators:
    when excited by an input of a characteristic functional form, the system’s output
    converges to a constant value only depending on the nth (nonlinear) derivative
    of the input.'
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Moritz
  full_name: Lang, Moritz
  id: 29E0800A-F248-11E8-B48F-1D18A9856A87
  last_name: Lang
- first_name: Eduardo
  full_name: Sontag, Eduardo
  last_name: Sontag
citation:
  ama: Lang M, Sontag E. Zeros of nonlinear systems with input invariances. <i>Automatica</i>.
    2017;81C:46-55. doi:<a href="https://doi.org/10.1016/j.automatica.2017.03.030">10.1016/j.automatica.2017.03.030</a>
  apa: Lang, M., &#38; Sontag, E. (2017). Zeros of nonlinear systems with input invariances.
    <i>Automatica</i>. International Federation of Automatic Control. <a href="https://doi.org/10.1016/j.automatica.2017.03.030">https://doi.org/10.1016/j.automatica.2017.03.030</a>
  chicago: Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input
    Invariances.” <i>Automatica</i>. International Federation of Automatic Control,
    2017. <a href="https://doi.org/10.1016/j.automatica.2017.03.030">https://doi.org/10.1016/j.automatica.2017.03.030</a>.
  ieee: M. Lang and E. Sontag, “Zeros of nonlinear systems with input invariances,”
    <i>Automatica</i>, vol. 81C. International Federation of Automatic Control, pp.
    46–55, 2017.
  ista: Lang M, Sontag E. 2017. Zeros of nonlinear systems with input invariances.
    Automatica. 81C, 46–55.
  mla: Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.”
    <i>Automatica</i>, vol. 81C, International Federation of Automatic Control, 2017,
    pp. 46–55, doi:<a href="https://doi.org/10.1016/j.automatica.2017.03.030">10.1016/j.automatica.2017.03.030</a>.
  short: M. Lang, E. Sontag, Automatica 81C (2017) 46–55.
date_created: 2018-12-11T11:49:39Z
date_published: 2017-06-01T00:00:00Z
date_updated: 2025-04-15T06:50:01Z
day: '01'
ddc:
- '000'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1016/j.automatica.2017.03.030
ec_funded: 1
external_id:
  isi:
  - '000403513900006'
file:
- access_level: open_access
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:11:29Z
  date_updated: 2018-12-12T10:11:29Z
  file_id: '4884'
  file_name: IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf
  file_size: 1401954
  relation: main_file
file_date_updated: 2018-12-12T10:11:29Z
fulldoi: https://doi.org/10.1016/j.automatica.2017.03.030
has_accepted_license: '1'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 46 - 55
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
publication: Automatica
publication_identifier:
  issn:
  - 0005-1098
publication_status: published
publisher: International Federation of Automatic Control
publist_id: '6391'
pubrep_id: '813'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Zeros of nonlinear systems with input invariances
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 81C
year: '2017'
...
---
_id: '954'
abstract:
- lang: eng
  text: Understanding the relation between genotype and phenotype remains a major
    challenge. The difficulty of predicting individual mutation effects, and particularly
    the interactions between them, has prevented the development of a comprehensive
    theory that links genotypic changes to their phenotypic effects. We show that
    a general thermodynamic framework for gene regulation, based on a biophysical
    understanding of protein-DNA binding, accurately predicts the sign of epistasis
    in a canonical cis-regulatory element consisting of overlapping RNA polymerase
    and repressor binding sites. Sign and magnitude of individual mutation effects
    are sufficient to predict the sign of epistasis and its environmental dependence.
    Thus, the thermodynamic model offers the correct null prediction for epistasis
    between mutations across DNA-binding sites. Our results indicate that a predictive
    theory for the effects of cis-regulatory mutations is possible from first principles,
    as long as the essential molecular mechanisms and the constraints these impose
    on a biological system are accounted for.
article_number: e25192
article_processing_charge: Yes
author:
- first_name: Mato
  full_name: Lagator, Mato
  id: 345D25EC-F248-11E8-B48F-1D18A9856A87
  last_name: Lagator
- first_name: Tiago
  full_name: Paixao, Tiago
  id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
  last_name: Paixao
  orcid: 0000-0003-2361-3953
- first_name: Nicholas H
  full_name: Barton, Nicholas H
  id: 4880FE40-F248-11E8-B48F-1D18A9856A87
  last_name: Barton
  orcid: 0000-0002-8548-5240
- first_name: Jonathan P
  full_name: Bollback, Jonathan P
  id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
  last_name: Bollback
  orcid: 0000-0002-4624-4612
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
citation:
  ama: Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature
    of epistasis in a canonical cis-regulatory element. <i>eLife</i>. 2017;6. doi:<a
    href="https://doi.org/10.7554/eLife.25192">10.7554/eLife.25192</a>
  apa: Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., &#38; Guet, C. C.
    (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element.
    <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.25192">https://doi.org/10.7554/eLife.25192</a>
  chicago: Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and
    Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory
    Element.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href="https://doi.org/10.7554/eLife.25192">https://doi.org/10.7554/eLife.25192</a>.
  ieee: M. Lagator, T. Paixao, N. H. Barton, J. P. Bollback, and C. C. Guet, “On the
    mechanistic nature of epistasis in a canonical cis-regulatory element,” <i>eLife</i>,
    vol. 6. eLife Sciences Publications, 2017.
  ista: Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. 2017. On the mechanistic
    nature of epistasis in a canonical cis-regulatory element. eLife. 6, e25192.
  mla: Lagator, Mato, et al. “On the Mechanistic Nature of Epistasis in a Canonical
    Cis-Regulatory Element.” <i>ELife</i>, vol. 6, e25192, eLife Sciences Publications,
    2017, doi:<a href="https://doi.org/10.7554/eLife.25192">10.7554/eLife.25192</a>.
  short: M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017).
date_created: 2018-12-11T11:49:23Z
date_published: 2017-05-18T00:00:00Z
date_updated: 2025-07-10T12:01:50Z
day: '18'
ddc:
- '576'
department:
- _id: CaGu
- _id: NiBa
- _id: JoBo
doi: 10.7554/eLife.25192
ec_funded: 1
external_id:
  isi:
  - '000404024800001'
file:
- access_level: open_access
  checksum: 59cdd4400fb41280122d414fea971546
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:17:49Z
  date_updated: 2020-07-14T12:48:16Z
  file_id: '5306'
  file_name: IST-2017-841-v1+1_elife-25192-v2.pdf
  file_size: 2441529
  relation: main_file
- access_level: open_access
  checksum: b69024880558b858eb8c5d47a92b6377
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:17:50Z
  date_updated: 2020-07-14T12:48:16Z
  file_id: '5307'
  file_name: IST-2017-841-v1+2_elife-25192-figures-v2.pdf
  file_size: 3752660
  relation: main_file
file_date_updated: 2020-07-14T12:48:16Z
fulldoi: https://doi.org/10.7554/eLife.25192
has_accepted_license: '1'
intvolume: '         6'
isi: 1
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 25B1EC9E-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618091'
  name: Speed of Adaptation in Population Genetics and Evolutionary Computation
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 2578D616-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '648440'
  name: Selective Barriers to Horizontal Gene Transfer
publication: eLife
publication_identifier:
  issn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
publist_id: '6460'
pubrep_id: '841'
quality_controlled: '1'
scopus_import: '1'
status: public
title: On the mechanistic nature of epistasis in a canonical cis-regulatory element
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 6
year: '2017'
...
---
_id: '655'
abstract:
- lang: eng
  text: 'The bacterial flagellum is a self-assembling nanomachine. The external flagellar
    filament, several times longer than a bacterial cell body, is made of a few tens
    of thousands subunits of a single protein: flagellin. A fundamental problem concerns
    the molecular mechanism of how the flagellum grows outside the cell, where no
    discernible energy source is available. Here, we monitored the dynamic assembly
    of individual flagella using in situ labelling and real-time immunostaining of
    elongating flagellar filaments. We report that the rate of flagellum growth, initially
    ~1,700 amino acids per second, decreases with length and that the previously proposed
    chain mechanism does not contribute to the filament elongation dynamics. Inhibition
    of the proton motive force-dependent export apparatus revealed a major contribution
    of substrate injection in driving filament elongation. The combination of experimental
    and mathematical evidence demonstrates that a simple, injection-diffusion mechanism
    controls bacterial flagella growth outside the cell.'
article_number: e23136
article_processing_charge: No
author:
- first_name: Thibaud
  full_name: Renault, Thibaud
  last_name: Renault
- first_name: Anthony
  full_name: Abraham, Anthony
  last_name: Abraham
- first_name: Tobias
  full_name: Bergmiller, Tobias
  id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
  last_name: Bergmiller
  orcid: 0000-0001-5396-4346
- first_name: Guillaume
  full_name: Paradis, Guillaume
  last_name: Paradis
- first_name: Simon
  full_name: Rainville, Simon
  last_name: Rainville
- first_name: Emmanuelle
  full_name: Charpentier, Emmanuelle
  last_name: Charpentier
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
- first_name: Yuhai
  full_name: Tu, Yuhai
  last_name: Tu
- first_name: Keiichi
  full_name: Namba, Keiichi
  last_name: Namba
- first_name: James
  full_name: Keener, James
  last_name: Keener
- first_name: Tohru
  full_name: Minamino, Tohru
  last_name: Minamino
- first_name: Marc
  full_name: Erhardt, Marc
  last_name: Erhardt
citation:
  ama: Renault T, Abraham A, Bergmiller T, et al. Bacterial flagella grow through
    an injection diffusion mechanism. <i>eLife</i>. 2017;6. doi:<a href="https://doi.org/10.7554/eLife.23136">10.7554/eLife.23136</a>
  apa: Renault, T., Abraham, A., Bergmiller, T., Paradis, G., Rainville, S., Charpentier,
    E., … Erhardt, M. (2017). Bacterial flagella grow through an injection diffusion
    mechanism. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.23136">https://doi.org/10.7554/eLife.23136</a>
  chicago: Renault, Thibaud, Anthony Abraham, Tobias Bergmiller, Guillaume Paradis,
    Simon Rainville, Emmanuelle Charpentier, Calin C Guet, et al. “Bacterial Flagella
    Grow through an Injection Diffusion Mechanism.” <i>ELife</i>. eLife Sciences Publications,
    2017. <a href="https://doi.org/10.7554/eLife.23136">https://doi.org/10.7554/eLife.23136</a>.
  ieee: T. Renault <i>et al.</i>, “Bacterial flagella grow through an injection diffusion
    mechanism,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.
  ista: Renault T, Abraham A, Bergmiller T, Paradis G, Rainville S, Charpentier E,
    Guet CC, Tu Y, Namba K, Keener J, Minamino T, Erhardt M. 2017. Bacterial flagella
    grow through an injection diffusion mechanism. eLife. 6, e23136.
  mla: Renault, Thibaud, et al. “Bacterial Flagella Grow through an Injection Diffusion
    Mechanism.” <i>ELife</i>, vol. 6, e23136, eLife Sciences Publications, 2017, doi:<a
    href="https://doi.org/10.7554/eLife.23136">10.7554/eLife.23136</a>.
  short: T. Renault, A. Abraham, T. Bergmiller, G. Paradis, S. Rainville, E. Charpentier,
    C.C. Guet, Y. Tu, K. Namba, J. Keener, T. Minamino, M. Erhardt, ELife 6 (2017).
date_created: 2018-12-11T11:47:44Z
date_published: 2017-03-06T00:00:00Z
date_updated: 2025-09-11T07:11:19Z
day: '06'
ddc:
- '579'
department:
- _id: CaGu
doi: 10.7554/eLife.23136
external_id:
  isi:
  - '000398680700001'
file:
- access_level: open_access
  checksum: 39e1c3e82ddac83a30422fa72fa1a383
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:08:53Z
  date_updated: 2020-07-14T12:47:33Z
  file_id: '4716'
  file_name: IST-2017-904-v1+1_elife-23136-v2.pdf
  file_size: 5520359
  relation: main_file
- access_level: open_access
  checksum: a6d542253028f52e00aa29739ddffe8f
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:08:54Z
  date_updated: 2020-07-14T12:47:33Z
  file_id: '4717'
  file_name: IST-2017-904-v1+2_elife-23136-figures-v2.pdf
  file_size: 11242920
  relation: main_file
file_date_updated: 2020-07-14T12:47:33Z
fulldoi: https://doi.org/10.7554/eLife.23136
has_accepted_license: '1'
intvolume: '         6'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
  issn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
publist_id: '7082'
pubrep_id: '904'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Bacterial flagella grow through an injection diffusion mechanism
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 6
year: '2017'
...
---
_id: '665'
abstract:
- lang: eng
  text: The molecular mechanisms underlying phenotypic variation in isogenic bacterial
    populations remain poorly understood.We report that AcrAB-TolC, the main multidrug
    efflux pump of Escherichia coli, exhibits a strong partitioning bias for old cell
    poles by a segregation mechanism that is mediated by ternary AcrAB-TolC complex
    formation. Mother cells inheriting old poles are phenotypically distinct and display
    increased drug efflux activity relative to daughters. Consequently, we find systematic
    and long-lived growth differences between mother and daughter cells in the presence
    of subinhibitory drug concentrations. A simple model for biased partitioning predicts
    a population structure of long-lived and highly heterogeneous phenotypes. This
    straightforward mechanism of generating sustained growth rate differences at subinhibitory
    antibiotic concentrations has implications for understanding the emergence of
    multidrug resistance in bacteria.
article_processing_charge: No
article_type: original
author:
- first_name: Tobias
  full_name: Bergmiller, Tobias
  id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
  last_name: Bergmiller
  orcid: 0000-0001-5396-4346
- first_name: Anna M
  full_name: Andersson, Anna M
  id: 2B8A40DA-F248-11E8-B48F-1D18A9856A87
  last_name: Andersson
  orcid: 0000-0003-2912-6769
- first_name: Kathrin
  full_name: Tomasek, Kathrin
  id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
  last_name: Tomasek
  orcid: 0000-0003-3768-877X
- first_name: Enrique
  full_name: Balleza, Enrique
  last_name: Balleza
- first_name: Daniel
  full_name: Kiviet, Daniel
  last_name: Kiviet
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Gasper
  full_name: Tkacik, Gasper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkacik
  orcid: 0000-0002-6699-1455
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
citation:
  ama: Bergmiller T, Andersson AM, Tomasek K, et al. Biased partitioning of the multidrug
    efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. <i>Science</i>.
    2017;356(6335):311-315. doi:<a href="https://doi.org/10.1126/science.aaf4762">10.1126/science.aaf4762</a>
  apa: Bergmiller, T., Andersson, A. M., Tomasek, K., Balleza, E., Kiviet, D., Hauschild,
    R., … Guet, C. C. (2017). Biased partitioning of the multidrug efflux pump AcrAB
    TolC underlies long lived phenotypic heterogeneity. <i>Science</i>. American Association
    for the Advancement of Science. <a href="https://doi.org/10.1126/science.aaf4762">https://doi.org/10.1126/science.aaf4762</a>
  chicago: Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza,
    Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning
    of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.”
    <i>Science</i>. American Association for the Advancement of Science, 2017. <a
    href="https://doi.org/10.1126/science.aaf4762">https://doi.org/10.1126/science.aaf4762</a>.
  ieee: T. Bergmiller <i>et al.</i>, “Biased partitioning of the multidrug efflux
    pump AcrAB TolC underlies long lived phenotypic heterogeneity,” <i>Science</i>,
    vol. 356, no. 6335. American Association for the Advancement of Science, pp. 311–315,
    2017.
  ista: Bergmiller T, Andersson AM, Tomasek K, Balleza E, Kiviet D, Hauschild R, Tkačik
    G, Guet CC. 2017. Biased partitioning of the multidrug efflux pump AcrAB TolC
    underlies long lived phenotypic heterogeneity. Science. 356(6335), 311–315.
  mla: Bergmiller, Tobias, et al. “Biased Partitioning of the Multidrug Efflux Pump
    AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” <i>Science</i>, vol.
    356, no. 6335, American Association for the Advancement of Science, 2017, pp.
    311–15, doi:<a href="https://doi.org/10.1126/science.aaf4762">10.1126/science.aaf4762</a>.
  short: T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild,
    G. Tkačik, C.C. Guet, Science 356 (2017) 311–315.
corr_author: '1'
date_created: 2018-12-11T11:47:48Z
date_published: 2017-04-21T00:00:00Z
date_updated: 2025-09-11T07:05:04Z
day: '21'
department:
- _id: CaGu
- _id: GaTk
- _id: Bio
doi: 10.1126/science.aaf4762
external_id:
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fulldoi: https://doi.org/10.1126/science.aaf4762
intvolume: '       356'
isi: 1
issue: '6335'
language:
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month: '04'
oa_version: None
page: 311 - 315
project:
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  call_identifier: FWF
  grant_number: P28844-B27
  name: Biophysics of information processing in gene regulation
publication: Science
publication_identifier:
  issn:
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publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '7064'
quality_controlled: '1'
related_material:
  record:
  - id: '5560'
    relation: popular_science
    status: public
scopus_import: '1'
status: public
title: Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long
  lived phenotypic heterogeneity
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 356
year: '2017'
...
