---
_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. Acta Informatica. 2017;54(8):765-787.
doi:10.1007/s00236-016-0278-x
apa: Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., & Petrov,
T. (2017). Model checking the evolution of gene regulatory networks. Acta Informatica.
Springer. https://doi.org/10.1007/s00236-016-0278-x
chicago: Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago
Paixao, and Tatjana Petrov. “Model Checking the Evolution of Gene Regulatory Networks.”
Acta Informatica. Springer, 2017. https://doi.org/10.1007/s00236-016-0278-x.
ieee: M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov,
“Model checking the evolution of gene regulatory networks,” Acta Informatica,
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.”
Acta Informatica, vol. 54, no. 8, Springer, 2017, pp. 765–87, doi:10.1007/s00236-016-0278-x.
short: M. Giacobbe, C.C. Guet, A. Gupta, T.A. Henzinger, T. Paixao, T. Petrov, Acta
Informatica 54 (2017) 765–787.
date_created: 2018-12-11T11:51:32Z
date_published: 2017-12-01T00:00:00Z
date_updated: 2023-09-20T11:06:03Z
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:
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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
has_accepted_license: '1'
intvolume: ' 54'
isi: 1
issue: '8'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
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: The Wittgenstein Prize
- _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:
- '00015903'
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 54
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. Algorithmica. 2017;78(2):681-713.
doi:10.1007/s00453-016-0212-1
apa: Paixao, T., Pérez Heredia, J., Sudholt, D., & Trubenova, B. (2017). Towards
a runtime comparison of natural and artificial evolution. Algorithmica.
Springer. https://doi.org/10.1007/s00453-016-0212-1
chicago: Paixao, Tiago, Jorge Pérez Heredia, Dirk Sudholt, and Barbora Trubenova.
“Towards a Runtime Comparison of Natural and Artificial Evolution.” Algorithmica.
Springer, 2017. https://doi.org/10.1007/s00453-016-0212-1.
ieee: T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “Towards a runtime
comparison of natural and artificial evolution,” Algorithmica, 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.” Algorithmica, vol. 78, no. 2, Springer, 2017, pp. 681–713,
doi:10.1007/s00453-016-0212-1.
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: 2023-09-20T11:14:42Z
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
relation: main_file
file_date_updated: 2020-07-14T12:44:44Z
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:
- '01784617'
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 78
year: '2017'
...
---
_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.
Molecular Microbiology. 2017;104(1):16-31. doi:10.1111/mmi.13597
apa: Fang, C., Nagy-Staron, A. A., 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.
Wiley-Blackwell. https://doi.org/10.1111/mmi.13597
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.” Molecular
Microbiology. Wiley-Blackwell, 2017. https://doi.org/10.1111/mmi.13597.
ieee: C. Fang et al., “Insulation and wiring specificity of BceR like response
regulators and their target promoters in Bacillus subtilis,” Molecular Microbiology,
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.” Molecular Microbiology,
vol. 104, no. 1, Wiley-Blackwell, 2017, pp. 16–31, doi:10.1111/mmi.13597.
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: 2023-09-20T11:48:43Z
day: '01'
department:
- _id: CaGu
doi: 10.1111/mmi.13597
external_id:
isi:
- '000398059200002'
intvolume: ' 104'
isi: 1
issue: '1'
language:
- iso: eng
month: '04'
oa_version: None
page: 16 - 31
publication: Molecular Microbiology
publication_identifier:
issn:
- ' 0950382X'
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 104
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. eLife. 2017;6. doi:10.7554/eLife.25192
apa: Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., & Guet, C. C.
(2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element.
ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25192
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.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25192.
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,” eLife,
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.” ELife, vol. 6, e25192, eLife Sciences Publications,
2017, doi:10.7554/eLife.25192.
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: 2023-09-22T10:01:17Z
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
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:
- 2050084X
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 6
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) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>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. Automatica.
2017;81C:46-55. doi:10.1016/j.automatica.2017.03.030
apa: Lang, M., & Sontag, E. (2017). Zeros of nonlinear systems with input invariances.
Automatica. International Federation of Automatic Control. https://doi.org/10.1016/j.automatica.2017.03.030
chicago: Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input
Invariances.” Automatica. International Federation of Automatic Control,
2017. https://doi.org/10.1016/j.automatica.2017.03.030.
ieee: M. Lang and E. Sontag, “Zeros of nonlinear systems with input invariances,”
Automatica, 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.”
Automatica, vol. 81C, International Federation of Automatic Control, 2017,
pp. 46–55, doi:10.1016/j.automatica.2017.03.030.
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: 2023-10-17T08:51:18Z
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
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: '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. Science.
2017;356(6335):311-315. doi:10.1126/science.aaf4762
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. Science. American Association
for the Advancement of Science. https://doi.org/10.1126/science.aaf4762
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.”
Science. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/science.aaf4762.
ieee: T. Bergmiller et al., “Biased partitioning of the multidrug efflux
pump AcrAB TolC underlies long lived phenotypic heterogeneity,” Science,
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.” Science, vol.
356, no. 6335, American Association for the Advancement of Science, 2017, pp.
311–15, doi:10.1126/science.aaf4762.
short: T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild,
G. Tkačik, C.C. Guet, Science 356 (2017) 311–315.
date_created: 2018-12-11T11:47:48Z
date_published: 2017-04-21T00:00:00Z
date_updated: 2024-02-21T13:49:00Z
day: '21'
department:
- _id: CaGu
- _id: GaTk
- _id: Bio
doi: 10.1126/science.aaf4762
intvolume: ' 356'
issue: '6335'
language:
- iso: eng
month: '04'
oa_version: None
page: 311 - 315
project:
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: Science
publication_identifier:
issn:
- '00368075'
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 356
year: '2017'
...
---
_id: '1028'
abstract:
- lang: eng
text: Optogenetics and photopharmacology provide spatiotemporally precise control
over protein interactions and protein function in cells and animals. Optogenetic
methods that are sensitive to green light and can be used to break protein complexes
are not broadly available but would enable multichromatic experiments with previously
inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12)
binding domains of bacterial CarH transcription factors for green-light-induced
receptor dissociation. In cultured cells, we observed oligomerization-induced
cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding
domains in the dark that was rapidly eliminated upon illumination. In zebrafish
embryos expressing fusion receptors, green light endowed control over aberrant
fibroblast growth factor signaling during development. Green-light-induced domain
dissociation and light-inactivated receptors will critically expand the optogenetic
toolbox for control of biological processes.
acknowledgement: "This work was supported by a grant from the European Union\U0010FC1Ds
Seventh Framework Programme (CIG-303564). E.R. was supported by the graduate program
MolecularDrugTargets (Austrian Science Fund (FWF), W1232) and a FemTech fellowship
(Austrian Research Promotion Agency, 3580812)"
article_processing_charge: No
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. Green-light-induced
inactivation of receptor signaling using cobalamin-binding domains. Angewandte
Chemie - International Edition. 2017;56(16):4608-4611. doi:10.1002/anie.201611998
apa: Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., & Janovjak,
H. L. (2017). Green-light-induced inactivation of receptor signaling using cobalamin-binding
domains. Angewandte Chemie - International Edition. Wiley-Blackwell. https://doi.org/10.1002/anie.201611998
chicago: Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel,
and Harald L Janovjak. “Green-Light-Induced Inactivation of Receptor Signaling
Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition.
Wiley-Blackwell, 2017. https://doi.org/10.1002/anie.201611998.
ieee: S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak,
“Green-light-induced inactivation of receptor signaling using cobalamin-binding
domains,” Angewandte Chemie - International Edition, vol. 56, no. 16. Wiley-Blackwell,
pp. 4608–4611, 2017.
ista: Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017.
Green-light-induced inactivation of receptor signaling using cobalamin-binding
domains. Angewandte Chemie - International Edition. 56(16), 4608–4611.
mla: Kainrath, Stephanie, et al. “Green-Light-Induced Inactivation of Receptor Signaling
Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition,
vol. 56, no. 16, Wiley-Blackwell, 2017, pp. 4608–11, doi:10.1002/anie.201611998.
short: S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak,
Angewandte Chemie - International Edition 56 (2017) 4608–4611.
date_created: 2018-12-11T11:49:46Z
date_published: 2017-03-20T00:00:00Z
date_updated: 2024-03-27T23:30:13Z
day: '20'
ddc:
- '540'
department:
- _id: CaGu
- _id: HaJa
doi: 10.1002/anie.201611998
ec_funded: 1
external_id:
isi:
- '000398154000038'
file:
- access_level: open_access
content_type: application/pdf
creator: dernst
date_created: 2019-01-18T09:39:55Z
date_updated: 2019-01-18T09:39:55Z
file_id: '5845'
file_name: 2017_communications_Kainrath.pdf
file_size: 2614942
relation: main_file
success: 1
file_date_updated: 2019-01-18T09:39:55Z
has_accepted_license: '1'
intvolume: ' 56'
isi: 1
issue: '16'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 4608-4611
project:
- _id: 25548C20-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '303564'
name: Microbial Ion Channels for Synthetic Neurobiology
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets [do not use to be deleted]
publication: Angewandte Chemie - International Edition
publication_identifier:
issn:
- '14337851'
publication_status: published
publisher: Wiley-Blackwell
publist_id: '6362'
quality_controlled: '1'
related_material:
record:
- id: '418'
relation: dissertation_contains
status: public
- id: '7680'
relation: part_of_dissertation
status: public
scopus_import: '1'
status: public
title: Green-light-induced inactivation of receptor signaling using cobalamin-binding
domains
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: 56
year: '2017'
...
---
_id: '704'
abstract:
- lang: eng
text: 'How the organization of genes on a chromosome shapes adaptation is essential
for understanding evolutionary paths. Here, we investigate how adaptation to rapidly
increasing levels of antibiotic depends on the chromosomal neighborhood of a drug-resistance
gene inserted at different positions of the Escherichia coli chromosome. Using
a dual-fluorescence reporter that allows us to distinguish gene amplifications
from other up-mutations, we track in real-time adaptive changes in expression
of the drug-resistance gene. We find that the relative contribution of several
mutation types differs systematically between loci due to properties of neighboring
genes: essentiality, expression, orientation, termination, and presence of duplicates.
These properties determine rate and fitness effects of gene amplification, deletions,
and mutations compromising transcriptional termination. Thus, the adaptive potential
of a gene under selection is a system-property with a complex genetic basis that
is specific for each chromosomal locus, and it can be inferred from detailed functional
and genomic data.'
article_number: e25100
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. Complex chromosomal neighborhood effects determine the
adaptive potential of a gene under selection. eLife. 2017;6. doi:10.7554/eLife.25100
apa: Steinrück, M., & Guet, C. C. (2017). Complex chromosomal neighborhood effects
determine the adaptive potential of a gene under selection. ELife. eLife
Sciences Publications. https://doi.org/10.7554/eLife.25100
chicago: Steinrück, Magdalena, and Calin C Guet. “Complex Chromosomal Neighborhood
Effects Determine the Adaptive Potential of a Gene under Selection.” ELife.
eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25100.
ieee: M. Steinrück and C. C. Guet, “Complex chromosomal neighborhood effects determine
the adaptive potential of a gene under selection,” eLife, vol. 6. eLife
Sciences Publications, 2017.
ista: Steinrück M, Guet CC. 2017. Complex chromosomal neighborhood effects determine
the adaptive potential of a gene under selection. eLife. 6, e25100.
mla: Steinrück, Magdalena, and Calin C. Guet. “Complex Chromosomal Neighborhood
Effects Determine the Adaptive Potential of a Gene under Selection.” ELife,
vol. 6, e25100, eLife Sciences Publications, 2017, doi:10.7554/eLife.25100.
short: M. Steinrück, C.C. Guet, ELife 6 (2017).
date_created: 2018-12-11T11:48:01Z
date_published: 2017-07-25T00:00:00Z
date_updated: 2024-03-27T23:30:27Z
day: '25'
ddc:
- '576'
department:
- _id: CaGu
doi: 10.7554/eLife.25100
file:
- access_level: open_access
checksum: 6b908b5db9f61f6820ebd7f8fa815571
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:12:54Z
date_updated: 2020-07-14T12:47:48Z
file_id: '4975'
file_name: IST-2017-890-v1+1_elife-25100-v1.pdf
file_size: 2092088
relation: main_file
- access_level: open_access
checksum: ca21530389b720243552678125fdba35
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:12:55Z
date_updated: 2020-07-14T12:47:48Z
file_id: '4976'
file_name: IST-2017-890-v1+2_elife-25100-figures-v1.pdf
file_size: 3428681
relation: main_file
file_date_updated: 2020-07-14T12:47:48Z
has_accepted_license: '1'
intvolume: ' 6'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
issn:
- 2050084X
publication_status: published
publisher: eLife Sciences Publications
publist_id: '6990'
pubrep_id: '890'
quality_controlled: '1'
related_material:
record:
- id: '5564'
relation: popular_science
status: public
- id: '26'
relation: dissertation_contains
status: public
scopus_import: 1
status: public
title: Complex chromosomal neighborhood effects determine the adaptive potential of
a gene under selection
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: '696'
abstract:
- lang: eng
text: Mutator strains are expected to evolve when the availability and effect of
beneficial mutations are high enough to counteract the disadvantage from deleterious
mutations that will inevitably accumulate. As the population becomes more adapted
to its environment, both availability and effect of beneficial mutations necessarily
decrease and mutation rates are predicted to decrease. It has been shown that
certain molecular mechanisms can lead to increased mutation rates when the organism
finds itself in a stressful environment. While this may be a correlated response
to other functions, it could also be an adaptive mechanism, raising mutation rates
only when it is most advantageous. Here, we use a mathematical model to investigate
the plausibility of the adaptive hypothesis. We show that such a mechanism can
be mantained if the population is subjected to diverse stresses. By simulating
various antibiotic treatment schemes, we find that combination treatments can
reduce the effectiveness of second-order selection on stress-induced mutagenesis.
We discuss the implications of our results to strategies of antibiotic therapy.
article_number: e1005609
article_type: original
author:
- first_name: Marta
full_name: Lukacisinova, Marta
id: 4342E402-F248-11E8-B48F-1D18A9856A87
last_name: Lukacisinova
orcid: 0000-0002-2519-8004
- first_name: Sebastian
full_name: Novak, Sebastian
id: 461468AE-F248-11E8-B48F-1D18A9856A87
last_name: Novak
orcid: 0000-0002-2519-824X
- first_name: Tiago
full_name: Paixao, Tiago
id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
last_name: Paixao
orcid: 0000-0003-2361-3953
citation:
ama: 'Lukacisinova M, Novak S, Paixao T. Stress induced mutagenesis: Stress diversity
facilitates the persistence of mutator genes. PLoS Computational Biology.
2017;13(7). doi:10.1371/journal.pcbi.1005609'
apa: 'Lukacisinova, M., Novak, S., & Paixao, T. (2017). Stress induced mutagenesis:
Stress diversity facilitates the persistence of mutator genes. PLoS Computational
Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609'
chicago: 'Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Stress Induced
Mutagenesis: Stress Diversity Facilitates the Persistence of Mutator Genes.” PLoS
Computational Biology. Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.'
ieee: 'M. Lukacisinova, S. Novak, and T. Paixao, “Stress induced mutagenesis: Stress
diversity facilitates the persistence of mutator genes,” PLoS Computational
Biology, vol. 13, no. 7. Public Library of Science, 2017.'
ista: 'Lukacisinova M, Novak S, Paixao T. 2017. Stress induced mutagenesis: Stress
diversity facilitates the persistence of mutator genes. PLoS Computational Biology.
13(7), e1005609.'
mla: 'Lukacisinova, Marta, et al. “Stress Induced Mutagenesis: Stress Diversity
Facilitates the Persistence of Mutator Genes.” PLoS Computational Biology,
vol. 13, no. 7, e1005609, Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.'
short: M. Lukacisinova, S. Novak, T. Paixao, PLoS Computational Biology 13 (2017).
date_created: 2018-12-11T11:47:58Z
date_published: 2017-07-18T00:00:00Z
date_updated: 2024-03-27T23:30:28Z
day: '18'
ddc:
- '576'
department:
- _id: ToBo
- _id: NiBa
- _id: CaGu
doi: 10.1371/journal.pcbi.1005609
ec_funded: 1
file:
- access_level: open_access
checksum: 9143c290fa6458ed2563bff4b295554a
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:15:01Z
date_updated: 2020-07-14T12:47:46Z
file_id: '5117'
file_name: IST-2017-894-v1+1_journal.pcbi.1005609.pdf
file_size: 3775716
relation: main_file
file_date_updated: 2020-07-14T12:47:46Z
has_accepted_license: '1'
intvolume: ' 13'
issue: '7'
language:
- iso: eng
month: '07'
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
publication: PLoS Computational Biology
publication_identifier:
issn:
- 1553734X
publication_status: published
publisher: Public Library of Science
publist_id: '7004'
pubrep_id: '894'
quality_controlled: '1'
related_material:
record:
- id: '9849'
relation: research_data
status: public
- id: '9850'
relation: research_data
status: public
- id: '9851'
relation: research_data
status: public
- id: '9852'
relation: research_data
status: public
- id: '6263'
relation: dissertation_contains
status: public
scopus_import: 1
status: public
title: 'Stress induced mutagenesis: Stress diversity facilitates the persistence of
mutator genes'
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: 13
year: '2017'
...
---
_id: '735'
abstract:
- lang: eng
text: Cell-cell contact formation constitutes an essential step in evolution, leading
to the differentiation of specialized cell types. However, remarkably little is
known about whether and how the interplay between contact formation and fate specification
affects development. Here, we identify a positive feedback loop between cell-cell
contact duration, morphogen signaling, and mesendoderm cell-fate specification
during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance
the competence of prechordal plate (ppl) progenitor cells to respond to Nodal
signaling, required for ppl cell-fate specification. We further show that Nodal
signaling promotes ppl cell-cell contact duration, generating a positive feedback
loop between ppl cell-cell contact duration and cell-fate specification. Finally,
by combining mathematical modeling and experimentation, we show that this feedback
determines whether anterior axial mesendoderm cells become ppl or, instead, turn
into endoderm. Thus, the interdependent activities of cell-cell signaling and
contact formation control fate diversification within the developing embryo.
article_processing_charge: No
author:
- first_name: Vanessa
full_name: Barone, Vanessa
id: 419EECCC-F248-11E8-B48F-1D18A9856A87
last_name: Barone
orcid: 0000-0003-2676-3367
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Gabriel
full_name: Krens, Gabriel
id: 2B819732-F248-11E8-B48F-1D18A9856A87
last_name: Krens
orcid: 0000-0003-4761-5996
- first_name: Saurabh
full_name: Pradhan, Saurabh
last_name: Pradhan
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
- first_name: Keisuke
full_name: Sako, Keisuke
id: 3BED66BE-F248-11E8-B48F-1D18A9856A87
last_name: Sako
orcid: 0000-0002-6453-8075
- first_name: Mateusz K
full_name: Sikora, Mateusz K
id: 2F74BCDE-F248-11E8-B48F-1D18A9856A87
last_name: Sikora
- 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: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
citation:
ama: Barone V, Lang M, Krens G, et al. An effective feedback loop between cell-cell
contact duration and morphogen signaling determines cell fate. Developmental
Cell. 2017;43(2):198-211. doi:10.1016/j.devcel.2017.09.014
apa: Barone, V., Lang, M., Krens, G., Pradhan, S., Shamipour, S., Sako, K., … Heisenberg,
C.-P. J. (2017). An effective feedback loop between cell-cell contact duration
and morphogen signaling determines cell fate. Developmental Cell. Cell
Press. https://doi.org/10.1016/j.devcel.2017.09.014
chicago: Barone, Vanessa, Moritz Lang, Gabriel Krens, Saurabh Pradhan, Shayan Shamipour,
Keisuke Sako, Mateusz K Sikora, Calin C Guet, and Carl-Philipp J Heisenberg. “An
Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling
Determines Cell Fate.” Developmental Cell. Cell Press, 2017. https://doi.org/10.1016/j.devcel.2017.09.014.
ieee: V. Barone et al., “An effective feedback loop between cell-cell contact
duration and morphogen signaling determines cell fate,” Developmental Cell,
vol. 43, no. 2. Cell Press, pp. 198–211, 2017.
ista: Barone V, Lang M, Krens G, Pradhan S, Shamipour S, Sako K, Sikora MK, Guet
CC, Heisenberg C-PJ. 2017. An effective feedback loop between cell-cell contact
duration and morphogen signaling determines cell fate. Developmental Cell. 43(2),
198–211.
mla: Barone, Vanessa, et al. “An Effective Feedback Loop between Cell-Cell Contact
Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell,
vol. 43, no. 2, Cell Press, 2017, pp. 198–211, doi:10.1016/j.devcel.2017.09.014.
short: V. Barone, M. Lang, G. Krens, S. Pradhan, S. Shamipour, K. Sako, M.K. Sikora,
C.C. Guet, C.-P.J. Heisenberg, Developmental Cell 43 (2017) 198–211.
date_created: 2018-12-11T11:48:13Z
date_published: 2017-10-23T00:00:00Z
date_updated: 2024-03-27T23:30:38Z
day: '23'
department:
- _id: CaHe
- _id: CaGu
- _id: GaTk
doi: 10.1016/j.devcel.2017.09.014
ec_funded: 1
external_id:
isi:
- '000413443700011'
intvolume: ' 43'
isi: 1
issue: '2'
language:
- iso: eng
month: '10'
oa_version: None
page: 198 - 211
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 252DD2A6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I2058
name: 'Cell segregation in gastrulation: the role of cell fate specification'
publication: Developmental Cell
publication_identifier:
issn:
- '15345807'
publication_status: published
publisher: Cell Press
publist_id: '6934'
quality_controlled: '1'
related_material:
record:
- id: '961'
relation: dissertation_contains
status: public
- id: '8350'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: An effective feedback loop between cell-cell contact duration and morphogen
signaling determines cell fate
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 43
year: '2017'
...
---
_id: '1008'
abstract:
- lang: eng
text: Feedback loops in biological networks, among others, enable differentiation
and cell cycle progression, and increase robustness in signal transduction. In
natural networks, feedback loops are often complex and intertwined, making it
challenging to identify which loops are mainly responsible for an observed behavior.
However, minimal synthetic replicas could allow for such identification. Here,
we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae
to analyze if a transport-mediated positive feedback loop could be a core mechanism
for the switch-like behavior in the regulation of metabolic gene networks such
as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized
the synthetic circuit using deterministic and stochastic mathematical models.
Similar to its natural counterparts, our synthetic system shows bistable and hysteretic
behavior, and the inducer concentration range for bistability as well as the switching
rates between the two stable states depend on the repressor concentration. Our
results indicate that a generic permease–inducer–repressor circuit with a single
feedback loop is sufficient to explain the experimentally observed bistable behavior
of the natural systems. We anticipate that the approach of reimplementing natural
systems with orthogonal parts to identify crucial network components is applicable
to other natural systems such as signaling pathways.
acknowledgement: We thank Julio Polaina (Instituto de Agroqu ı ́ mica y Tecnolog ı
́ a de Alimentos, C.S.I.C., Paterna, Spain) for the gift of plasmid pMR4, Gregor
W. Schmidt for provision of and support with the micro fl uidic device, Markus Du
̈ rr for the cell tracking R script, and Lukas Widmer for the script for MEIGO using
“ parfor ” in MATLAB. We acknowledge the members of the Stelling group for discussions,
comments, and support.
author:
- first_name: Robert
full_name: Gnügge, Robert
last_name: Gnügge
- first_name: Lekshmi
full_name: Dharmarajan, Lekshmi
last_name: Dharmarajan
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Jörg
full_name: Stelling, Jörg
last_name: Stelling
citation:
ama: Gnügge R, Dharmarajan L, Lang M, Stelling J. An orthogonal permease–inducer–repressor
feedback loop shows bistability. ACS Synthetic Biology. 2016;5(10):1098-1107.
doi:10.1021/acssynbio.6b00013
apa: Gnügge, R., Dharmarajan, L., Lang, M., & Stelling, J. (2016). An orthogonal
permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology.
American Chemical Society. https://doi.org/10.1021/acssynbio.6b00013
chicago: Gnügge, Robert, Lekshmi Dharmarajan, Moritz Lang, and Jörg Stelling. “An
Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS
Synthetic Biology. American Chemical Society, 2016. https://doi.org/10.1021/acssynbio.6b00013.
ieee: R. Gnügge, L. Dharmarajan, M. Lang, and J. Stelling, “An orthogonal permease–inducer–repressor
feedback loop shows bistability,” ACS Synthetic Biology, vol. 5, no. 10.
American Chemical Society, pp. 1098–1107, 2016.
ista: Gnügge R, Dharmarajan L, Lang M, Stelling J. 2016. An orthogonal permease–inducer–repressor
feedback loop shows bistability. ACS Synthetic Biology. 5(10), 1098–1107.
mla: Gnügge, Robert, et al. “An Orthogonal Permease–Inducer–Repressor Feedback Loop
Shows Bistability.” ACS Synthetic Biology, vol. 5, no. 10, American Chemical
Society, 2016, pp. 1098–107, doi:10.1021/acssynbio.6b00013.
short: R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling, ACS Synthetic Biology 5
(2016) 1098–1107.
date_created: 2018-12-11T11:49:40Z
date_published: 2016-05-05T00:00:00Z
date_updated: 2021-01-12T06:47:37Z
day: '05'
department:
- _id: CaGu
doi: 10.1021/acssynbio.6b00013
intvolume: ' 5'
issue: '10'
language:
- iso: eng
month: '05'
oa_version: None
page: 1098 - 1107
publication: ACS Synthetic Biology
publication_status: published
publisher: American Chemical Society
publist_id: '6390'
quality_controlled: '1'
status: public
title: An orthogonal permease–inducer–repressor feedback loop shows bistability
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2016'
...
---
_id: '1170'
abstract:
- lang: eng
text: The increasing complexity of dynamic models in systems and synthetic biology
poses computational challenges especially for the identification of model parameters.
While modularization of the corresponding optimization problems could help reduce
the “curse of dimensionality,” abundant feedback and crosstalk mechanisms prohibit
a simple decomposition of most biomolecular networks into subnetworks, or modules.
Drawing on ideas from network modularization and multiple-shooting optimization,
we present here a modular parameter identification approach that explicitly allows
for such interdependencies. Interfaces between our modules are given by the experimentally
measured molecular species. This definition allows deriving good (initial) estimates
for the inter-module communication directly from the experimental data. Given
these estimates, the states and parameter sensitivities of different modules can
be integrated independently. To achieve consistency between modules, we iteratively
adjust the estimates for inter-module communication while optimizing the parameters.
After convergence to an optimal parameter set---but not during earlier iterations---the
intermodule communication as well as the individual modules\' state dynamics agree
with the dynamics of the nonmodularized network. Our modular parameter identification
approach allows for easy parallelization; it can reduce the computational complexity
for larger networks and decrease the probability to converge to suboptimal local
minima. We demonstrate the algorithm\'s performance in parameter estimation for
two biomolecular networks, a synthetic genetic oscillator and a mammalian signaling
pathway.
author:
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Jörg
full_name: Stelling, Jörg
last_name: Stelling
citation:
ama: Lang M, Stelling J. Modular parameter identification of biomolecular networks.
SIAM Journal on Scientific Computing. 2016;38(6):B988-B1008. doi:10.1137/15M103306X
apa: Lang, M., & Stelling, J. (2016). Modular parameter identification of biomolecular
networks. SIAM Journal on Scientific Computing. Society for Industrial
and Applied Mathematics . https://doi.org/10.1137/15M103306X
chicago: Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular
Networks.” SIAM Journal on Scientific Computing. Society for Industrial
and Applied Mathematics , 2016. https://doi.org/10.1137/15M103306X.
ieee: M. Lang and J. Stelling, “Modular parameter identification of biomolecular
networks,” SIAM Journal on Scientific Computing, vol. 38, no. 6. Society
for Industrial and Applied Mathematics , pp. B988–B1008, 2016.
ista: Lang M, Stelling J. 2016. Modular parameter identification of biomolecular
networks. SIAM Journal on Scientific Computing. 38(6), B988–B1008.
mla: Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular
Networks.” SIAM Journal on Scientific Computing, vol. 38, no. 6, Society
for Industrial and Applied Mathematics , 2016, pp. B988–1008, doi:10.1137/15M103306X.
short: M. Lang, J. Stelling, SIAM Journal on Scientific Computing 38 (2016) B988–B1008.
date_created: 2018-12-11T11:50:31Z
date_published: 2016-11-15T00:00:00Z
date_updated: 2021-01-12T06:48:49Z
day: '15'
ddc:
- '003'
- '518'
- '570'
- '621'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1137/15M103306X
file:
- access_level: local
checksum: 781bc3ffd30b2dd65b7727c5a285fc78
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:14:41Z
date_updated: 2020-07-14T12:44:37Z
file_id: '5095'
file_name: IST-2017-811-v1+1_modular_parameter_identification.pdf
file_size: 871964
relation: main_file
file_date_updated: 2020-07-14T12:44:37Z
has_accepted_license: '1'
intvolume: ' 38'
issue: '6'
language:
- iso: eng
month: '11'
oa_version: Submitted Version
page: B988 - B1008
publication: SIAM Journal on Scientific Computing
publication_status: published
publisher: 'Society for Industrial and Applied Mathematics '
publist_id: '6186'
pubrep_id: '811'
quality_controlled: '1'
scopus_import: 1
status: public
title: Modular parameter identification of biomolecular networks
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 38
year: '2016'
...
---
_id: '1220'
abstract:
- lang: eng
text: Theoretical and numerical aspects of aerodynamic efficiency of propulsion
systems coupled to the boundary layer of a fuselage are studied. We discuss the
effects of local flow fields, which are affected both by conservative flow acceleration
as well as total pressure losses, on the efficiency of boundary layer immersed
propulsion devices. We introduce the concept of a boundary layer retardation turbine
that helps reduce skin friction over the fuselage. We numerically investigate
efficiency gains offered by boundary layer and wake interacting devices. We discuss
the results in terms of a total energy consumption framework and show that efficiency
gains of any device depend on all the other elements of the propulsion system.
author:
- first_name: Gregor
full_name: Mikić, Gregor
last_name: Mikić
- first_name: Alex
full_name: Stoll, Alex
last_name: Stoll
- first_name: Joe
full_name: Bevirt, Joe
last_name: Bevirt
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Mark
full_name: Moore, Mark
last_name: Moore
citation:
ama: 'Mikić G, Stoll A, Bevirt J, Grah R, Moore M. Fuselage boundary layer ingestion
propulsion applied to a thin haul commuter aircraft for optimal efficiency. In:
AIAA; 2016:1-19. doi:10.2514/6.2016-3764'
apa: 'Mikić, G., Stoll, A., Bevirt, J., Grah, R., & Moore, M. (2016). Fuselage
boundary layer ingestion propulsion applied to a thin haul commuter aircraft for
optimal efficiency (pp. 1–19). Presented at the AIAA: Aviation Technology, Integration,
and Operations Conference, Washington, D.C., USA: AIAA. https://doi.org/10.2514/6.2016-3764'
chicago: Mikić, Gregor, Alex Stoll, Joe Bevirt, Rok Grah, and Mark Moore. “Fuselage
Boundary Layer Ingestion Propulsion Applied to a Thin Haul Commuter Aircraft for
Optimal Efficiency,” 1–19. AIAA, 2016. https://doi.org/10.2514/6.2016-3764.
ieee: 'G. Mikić, A. Stoll, J. Bevirt, R. Grah, and M. Moore, “Fuselage boundary
layer ingestion propulsion applied to a thin haul commuter aircraft for optimal
efficiency,” presented at the AIAA: Aviation Technology, Integration, and Operations
Conference, Washington, D.C., USA, 2016, pp. 1–19.'
ista: 'Mikić G, Stoll A, Bevirt J, Grah R, Moore M. 2016. Fuselage boundary layer
ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency.
AIAA: Aviation Technology, Integration, and Operations Conference, 1–19.'
mla: Mikić, Gregor, et al. Fuselage Boundary Layer Ingestion Propulsion Applied
to a Thin Haul Commuter Aircraft for Optimal Efficiency. AIAA, 2016, pp. 1–19,
doi:10.2514/6.2016-3764.
short: G. Mikić, A. Stoll, J. Bevirt, R. Grah, M. Moore, in:, AIAA, 2016, pp. 1–19.
conference:
end_date: 2016-06-17
location: Washington, D.C., USA
name: 'AIAA: Aviation Technology, Integration, and Operations Conference'
start_date: 2016-06-13
date_created: 2018-12-11T11:50:47Z
date_published: 2016-06-01T00:00:00Z
date_updated: 2023-02-21T10:17:50Z
day: '01'
department:
- _id: CaGu
- _id: GaTk
doi: 10.2514/6.2016-3764
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://ntrs.nasa.gov/search.jsp?R=20160010167&hterms=Fuselage+boundary+layer+ingestion+propulsion+applied+thin+haul+commuter+aircraft+optimal+efficiency&qs=N%3D0%26Ntk%3DAll%26Ntt%3DFuselage%2520boundary%2520layer%2520ingestion%2520propulsion%2520applied%2520to%2520a%2520thin%2520haul%2520commuter%2520aircraft%2520for%2520optimal%2520efficiency%26Ntx%3Dmode%2520matchallpartial%26Nm%3D123%7CCollection%7CNASA%2520STI%7C%7C17%7CCollection%7CNACA
month: '06'
oa: 1
oa_version: Preprint
page: 1 - 19
publication_status: published
publisher: AIAA
publist_id: '6114'
quality_controlled: '1'
scopus_import: 1
status: public
title: Fuselage boundary layer ingestion propulsion applied to a thin haul commuter
aircraft for optimal efficiency
type: conference
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
year: '2016'
...
---
_id: '1290'
abstract:
- lang: eng
text: We developed a competition-based screening strategy to identify compounds
that invert the selective advantage of antibiotic resistance. Using our assay,
we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance
efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram.
Treating a tetracycline-resistant population with β-thujaplicin selects for loss
of the resistance gene, enabling an effective second-phase treatment with doxycycline.
acknowledgement: "This work was supported in part by National Institute of Allergy
and Infectious Diseases grant U54 AI057159, US National Institutes of Health grants
R01 GM081617 (to R.K.) and GM086258 (to J.C.), European Research Council FP7 ERC
grant 281891 (to R.K.) and a National Science Foundation Graduate Fellowship (to
L.K.S.).\r\n"
author:
- first_name: Laura
full_name: Stone, Laura
last_name: Stone
- first_name: Michael
full_name: Baym, Michael
last_name: Baym
- first_name: Tami
full_name: Lieberman, Tami
last_name: Lieberman
- 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: Jon
full_name: Clardy, Jon
last_name: Clardy
- first_name: Roy
full_name: Kishony, Roy
last_name: Kishony
citation:
ama: Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. Compounds that
select against the tetracycline-resistance efflux pump. Nature Chemical Biology.
2016;12(11):902-904. doi:10.1038/nchembio.2176
apa: Stone, L., Baym, M., Lieberman, T., Chait, R. P., Clardy, J., & Kishony,
R. (2016). Compounds that select against the tetracycline-resistance efflux pump.
Nature Chemical Biology. Nature Publishing Group. https://doi.org/10.1038/nchembio.2176
chicago: Stone, Laura, Michael Baym, Tami Lieberman, Remy P Chait, Jon Clardy, and
Roy Kishony. “Compounds That Select against the Tetracycline-Resistance Efflux
Pump.” Nature Chemical Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/nchembio.2176.
ieee: L. Stone, M. Baym, T. Lieberman, R. P. Chait, J. Clardy, and R. Kishony, “Compounds
that select against the tetracycline-resistance efflux pump,” Nature Chemical
Biology, vol. 12, no. 11. Nature Publishing Group, pp. 902–904, 2016.
ista: Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. 2016. Compounds
that select against the tetracycline-resistance efflux pump. Nature Chemical Biology.
12(11), 902–904.
mla: Stone, Laura, et al. “Compounds That Select against the Tetracycline-Resistance
Efflux Pump.” Nature Chemical Biology, vol. 12, no. 11, Nature Publishing
Group, 2016, pp. 902–04, doi:10.1038/nchembio.2176.
short: L. Stone, M. Baym, T. Lieberman, R.P. Chait, J. Clardy, R. Kishony, Nature
Chemical Biology 12 (2016) 902–904.
date_created: 2018-12-11T11:51:10Z
date_published: 2016-11-01T00:00:00Z
date_updated: 2021-01-12T06:49:39Z
day: '01'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1038/nchembio.2176
intvolume: ' 12'
issue: '11'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069154/
month: '11'
oa: 1
oa_version: Preprint
page: 902 - 904
publication: Nature Chemical Biology
publication_status: published
publisher: Nature Publishing Group
publist_id: '6026'
quality_controlled: '1'
scopus_import: 1
status: public
title: Compounds that select against the tetracycline-resistance efflux pump
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2016'
...
---
_id: '1320'
abstract:
- lang: eng
text: 'In recent years, several biomolecular systems have been shown to be scale-invariant
(SI), i.e. to show the same output dynamics when exposed to geometrically scaled
input signals (u → pu, p > 0) after pre-adaptation to accordingly scaled constant
inputs. In this article, we show that SI systems-as well as systems invariant
with respect to other input transformations-can realize nonlinear differential
operators: when excited by inputs obeying functional forms characteristic for
a given class of invariant systems, the systems'' outputs converge to constant
values directly quantifying the speed of the input.'
acknowledgement: 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 n° [291734]. Work supported
in part by grants AFOSR FA9550-14-1-0060 and NIH 1R01GM100473.
article_number: '7526722'
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. Scale-invariant systems realize nonlinear differential operators.
In: Vol 2016-July. IEEE; 2016. doi:10.1109/ACC.2016.7526722'
apa: 'Lang, M., & Sontag, E. (2016). Scale-invariant systems realize nonlinear
differential operators (Vol. 2016–July). Presented at the ACC: American Control
Conference, Boston, MA, USA: IEEE. https://doi.org/10.1109/ACC.2016.7526722'
chicago: Lang, Moritz, and Eduardo Sontag. “Scale-Invariant Systems Realize Nonlinear
Differential Operators,” Vol. 2016–July. IEEE, 2016. https://doi.org/10.1109/ACC.2016.7526722.
ieee: 'M. Lang and E. Sontag, “Scale-invariant systems realize nonlinear differential
operators,” presented at the ACC: American Control Conference, Boston, MA, USA,
2016, vol. 2016–July.'
ista: 'Lang M, Sontag E. 2016. Scale-invariant systems realize nonlinear differential
operators. ACC: American Control Conference vol. 2016–July, 7526722.'
mla: Lang, Moritz, and Eduardo Sontag. Scale-Invariant Systems Realize Nonlinear
Differential Operators. Vol. 2016–July, 7526722, IEEE, 2016, doi:10.1109/ACC.2016.7526722.
short: M. Lang, E. Sontag, in:, IEEE, 2016.
conference:
end_date: 2016-07-08
location: Boston, MA, USA
name: 'ACC: American Control Conference'
start_date: 2016-07-06
date_created: 2018-12-11T11:51:21Z
date_published: 2016-07-28T00:00:00Z
date_updated: 2021-01-12T06:49:51Z
day: '28'
ddc:
- '003'
- '621'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1109/ACC.2016.7526722
ec_funded: 1
file:
- access_level: local
checksum: 7219432b43defc62a0d45f48d4ce6a19
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:17Z
date_updated: 2020-07-14T12:44:43Z
file_id: '5203'
file_name: IST-2017-810-v1+1_root.pdf
file_size: 539166
relation: main_file
file_date_updated: 2020-07-14T12:44:43Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa_version: Preprint
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication_status: published
publisher: IEEE
publist_id: '5950'
pubrep_id: '810'
quality_controlled: '1'
scopus_import: 1
status: public
title: Scale-invariant systems realize nonlinear differential operators
type: conference
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 2016-July
year: '2016'
...
---
_id: '1332'
abstract:
- lang: eng
text: Antibiotic-sensitive and -resistant bacteria coexist in natural environments
with low, if detectable, antibiotic concentrations. Except possibly around localized
antibiotic sources, where resistance can provide a strong advantage, bacterial
fitness is dominated by stresses unaffected by resistance to the antibiotic. How
do such mixed and heterogeneous conditions influence the selective advantage or
disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels
of tetracyclines potentiate selection for or against tetracycline resistance around
localized sources of almost any toxin or stress. Furthermore, certain stresses
generate alternating rings of selection for and against resistance around a localized
source of the antibiotic. In these conditions, localized antibiotic sources, even
at high strengths, can actually produce a net selection against resistance to
the antibiotic. Our results show that interactions between the effects of an antibiotic
and other stresses in inhomogeneous environments can generate pervasive, complex
patterns of selection both for and against antibiotic resistance.
acknowledgement: This work was partially supported by US National Institutes of Health
grant R01-GM081617, Israeli Centers of Research Excellence I-CORE Program ISF Grant
No. 152/11, and the European Research Council FP7 ERC Grant 281891.
article_number: '10333'
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: Adam
full_name: Palmer, Adam
last_name: Palmer
- first_name: Idan
full_name: Yelin, Idan
last_name: Yelin
- first_name: Roy
full_name: Kishony, Roy
last_name: Kishony
citation:
ama: Chait RP, Palmer A, Yelin I, Kishony R. Pervasive selection for and against
antibiotic resistance in inhomogeneous multistress environments. Nature Communications.
2016;7. doi:10.1038/ncomms10333
apa: Chait, R. P., Palmer, A., Yelin, I., & Kishony, R. (2016). Pervasive selection
for and against antibiotic resistance in inhomogeneous multistress environments.
Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms10333
chicago: Chait, Remy P, Adam Palmer, Idan Yelin, and Roy Kishony. “Pervasive Selection
for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.”
Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms10333.
ieee: R. P. Chait, A. Palmer, I. Yelin, and R. Kishony, “Pervasive selection for
and against antibiotic resistance in inhomogeneous multistress environments,”
Nature Communications, vol. 7. Nature Publishing Group, 2016.
ista: Chait RP, Palmer A, Yelin I, Kishony R. 2016. Pervasive selection for and
against antibiotic resistance in inhomogeneous multistress environments. Nature
Communications. 7, 10333.
mla: Chait, Remy P., et al. “Pervasive Selection for and against Antibiotic Resistance
in Inhomogeneous Multistress Environments.” Nature Communications, vol.
7, 10333, Nature Publishing Group, 2016, doi:10.1038/ncomms10333.
short: R.P. Chait, A. Palmer, I. Yelin, R. Kishony, Nature Communications 7 (2016).
date_created: 2018-12-11T11:51:25Z
date_published: 2016-01-20T00:00:00Z
date_updated: 2021-01-12T06:49:57Z
day: '20'
ddc:
- '570'
- '579'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1038/ncomms10333
file:
- access_level: open_access
checksum: ef147bcbb8bd37e9079cf3ce06f5815d
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:13:52Z
date_updated: 2020-07-14T12:44:44Z
file_id: '5039'
file_name: IST-2016-662-v1+1_ncomms10333.pdf
file_size: 1844107
relation: main_file
file_date_updated: 2020-07-14T12:44:44Z
has_accepted_license: '1'
intvolume: ' 7'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_status: published
publisher: Nature Publishing Group
publist_id: '5936'
pubrep_id: '662'
quality_controlled: '1'
scopus_import: 1
status: public
title: Pervasive selection for and against antibiotic resistance in inhomogeneous
multistress environments
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 7
year: '2016'
...
---
_id: '1342'
abstract:
- lang: eng
text: A key aspect of bacterial survival is the ability to evolve while migrating
across spatially varying environmental challenges. Laboratory experiments, however,
often study evolution in well-mixed systems. Here, we introduce an experimental
device, the microbial evolution and growth arena (MEGA)-plate, in which bacteria
spread and evolved on a large antibiotic landscape (120 × 60 centimeters) that
allowed visual observation of mutation and selection in a migrating bacterial
front.While resistance increased consistently, multiple coexisting lineages diversified
both phenotypically and genotypically. Analyzing mutants at and behind the propagating
front,we found that evolution is not always led by the most resistant mutants;
highly resistant mutants may be trapped behindmore sensitive lineages.TheMEGA-plate
provides a versatile platformfor studying microbial adaption and directly visualizing
evolutionary dynamics.
author:
- first_name: Michael
full_name: Baym, Michael
last_name: Baym
- first_name: Tami
full_name: Lieberman, Tami
last_name: Lieberman
- first_name: Eric
full_name: Kelsic, Eric
last_name: Kelsic
- 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: Rotem
full_name: Gross, Rotem
last_name: Gross
- first_name: Idan
full_name: Yelin, Idan
last_name: Yelin
- first_name: Roy
full_name: Kishony, Roy
last_name: Kishony
citation:
ama: Baym M, Lieberman T, Kelsic E, et al. Spatiotemporal microbial evolution on
antibiotic landscapes. Science. 2016;353(6304):1147-1151. doi:10.1126/science.aag0822
apa: Baym, M., Lieberman, T., Kelsic, E., Chait, R. P., Gross, R., Yelin, I., &
Kishony, R. (2016). Spatiotemporal microbial evolution on antibiotic landscapes.
Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aag0822
chicago: Baym, Michael, Tami Lieberman, Eric Kelsic, Remy P Chait, Rotem Gross,
Idan Yelin, and Roy Kishony. “Spatiotemporal Microbial Evolution on Antibiotic
Landscapes.” Science. American Association for the Advancement of Science,
2016. https://doi.org/10.1126/science.aag0822.
ieee: M. Baym et al., “Spatiotemporal microbial evolution on antibiotic landscapes,”
Science, vol. 353, no. 6304. American Association for the Advancement of
Science, pp. 1147–1151, 2016.
ista: Baym M, Lieberman T, Kelsic E, Chait RP, Gross R, Yelin I, Kishony R. 2016.
Spatiotemporal microbial evolution on antibiotic landscapes. Science. 353(6304),
1147–1151.
mla: Baym, Michael, et al. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.”
Science, vol. 353, no. 6304, American Association for the Advancement of
Science, 2016, pp. 1147–51, doi:10.1126/science.aag0822.
short: M. Baym, T. Lieberman, E. Kelsic, R.P. Chait, R. Gross, I. Yelin, R. Kishony,
Science 353 (2016) 1147–1151.
date_created: 2018-12-11T11:51:29Z
date_published: 2016-09-09T00:00:00Z
date_updated: 2021-01-12T06:50:01Z
day: '09'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1126/science.aag0822
intvolume: ' 353'
issue: '6304'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534434/
month: '09'
oa: 1
oa_version: Preprint
page: 1147 - 1151
publication: Science
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '5911'
quality_controlled: '1'
scopus_import: 1
status: public
title: Spatiotemporal microbial evolution on antibiotic landscapes
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 353
year: '2016'
...
---
_id: '1349'
abstract:
- lang: eng
text: Crossing fitness valleys is one of the major obstacles to function optimization.
In this paper we investigate how the structure of the fitness valley, namely its
depth d and length ℓ, influence the runtime of different strategies for crossing
these valleys. We present a runtime comparison between the (1+1) EA and two non-elitist
nature-inspired algorithms, Strong Selection Weak Mutation (SSWM) and the Metropolis
algorithm. While the (1+1) EA has to jump across the valley to a point of higher
fitness because it does not accept decreasing moves, the non-elitist algorithms
may cross the valley by accepting worsening moves. We show that while the runtime
of the (1+1) EA algorithm depends critically on the length of the valley, the
runtimes of the non-elitist algorithms depend crucially only on the depth of the
valley. In particular, the expected runtime of both SSWM and Metropolis is polynomial
in ℓ and exponential in d while the (1+1) EA is efficient only for valleys of
small length. Moreover, we show that both SSWM and Metropolis can also efficiently
optimize a rugged function consisting of consecutive valleys.
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: Heredia, Jorge
last_name: 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, Heredia J, Sudholt D, Trubenova B. When non-elitism outperforms
elitism for crossing fitness valleys. In: Proceedings of the Genetic and Evolutionary
Computation Conference 2016 . ACM; 2016:1163-1170. doi:10.1145/2908812.2908909'
apa: 'Oliveto, P., Paixao, T., Heredia, J., Sudholt, D., & Trubenova, B. (2016).
When non-elitism outperforms elitism for crossing fitness valleys. In Proceedings
of the Genetic and Evolutionary Computation Conference 2016 (pp. 1163–1170).
Denver, CO, USA: ACM. https://doi.org/10.1145/2908812.2908909'
chicago: Oliveto, Pietro, Tiago Paixao, Jorge Heredia, Dirk Sudholt, and Barbora
Trubenova. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.”
In Proceedings of the Genetic and Evolutionary Computation Conference 2016
, 1163–70. ACM, 2016. https://doi.org/10.1145/2908812.2908909.
ieee: P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, and B. Trubenova, “When non-elitism
outperforms elitism for crossing fitness valleys,” in Proceedings of the Genetic
and Evolutionary Computation Conference 2016 , Denver, CO, USA, 2016, pp.
1163–1170.
ista: 'Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. 2016. When non-elitism
outperforms elitism for crossing fitness valleys. Proceedings of the Genetic and
Evolutionary Computation Conference 2016 . GECCO: Genetic and evolutionary computation
conference, 1163–1170.'
mla: Oliveto, Pietro, et al. “When Non-Elitism Outperforms Elitism for Crossing
Fitness Valleys.” Proceedings of the Genetic and Evolutionary Computation Conference
2016 , ACM, 2016, pp. 1163–70, doi:10.1145/2908812.2908909.
short: P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, B. Trubenova, in:, Proceedings
of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–1170.
conference:
end_date: 2016-07-24
location: Denver, CO, USA
name: 'GECCO: Genetic and evolutionary computation conference'
start_date: 2016-07-20
date_created: 2018-12-11T11:51:31Z
date_published: 2016-07-20T00:00:00Z
date_updated: 2021-01-12T06:50:03Z
day: '20'
ddc:
- '576'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1145/2908812.2908909
ec_funded: 1
file:
- access_level: open_access
checksum: a1896e39e4113f2711e46b435d5f3e69
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:27Z
date_updated: 2020-07-14T12:44:45Z
file_id: '5214'
file_name: IST-2016-650-v1+1_p1163-oliveto.pdf
file_size: 979026
relation: main_file
file_date_updated: 2020-07-14T12:44:45Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1163 - 1170
project:
- _id: 25B1EC9E-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618091'
name: Speed of Adaptation in Population Genetics and Evolutionary Computation
publication: 'Proceedings of the Genetic and Evolutionary Computation Conference 2016 '
publication_status: published
publisher: ACM
publist_id: '5900'
pubrep_id: '650'
quality_controlled: '1'
scopus_import: 1
status: public
title: When non-elitism outperforms elitism for crossing fitness valleys
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: conference
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
year: '2016'
...
---
_id: '1359'
abstract:
- lang: eng
text: "The role of gene interactions in the evolutionary process has long\r\nbeen
controversial. Although some argue that they are not of\r\nimportance, because
most variation is additive, others claim that\r\ntheir effect in the long term
can be substantial. Here, we focus on\r\nthe long-term effects of genetic interactions
under directional\r\nselection assuming no mutation or dominance, and that epistasis
is\r\nsymmetrical overall. We ask by how much the mean of a complex\r\ntrait can
be increased by selection and analyze two extreme\r\nregimes, in which either
drift or selection dominate the dynamics\r\nof allele frequencies. In both scenarios,
epistatic interactions affect\r\nthe long-term response to selection by modulating
the additive\r\ngenetic variance. When drift dominates, we extend Robertson\r\n’\r\ns\r\n[Robertson
A (1960)\r\nProc R Soc Lond B Biol Sci\r\n153(951):234\r\n−\r\n249]\r\nargument
to show that, for any form of epistasis, the total response\r\nof a haploid population
is proportional to the initial total genotypic\r\nvariance. In contrast, the total
response of a diploid population is\r\nincreased by epistasis, for a given initial
genotypic variance. When\r\nselection dominates, we show that the total selection
response can\r\nonly be increased by epistasis when s\r\nome initially deleterious
alleles\r\nbecome favored as the genetic background changes. We find a sim-\r\nple
approximation for this effect and show that, in this regime, it is\r\nthe structure
of the genotype - phenotype map that matters and not\r\nthe variance components
of the population."
article_processing_charge: No
article_type: original
author:
- 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
citation:
ama: Paixao T, Barton NH. The effect of gene interactions on the long-term response
to selection. PNAS. 2016;113(16):4422-4427. doi:10.1073/pnas.1518830113
apa: Paixao, T., & Barton, N. H. (2016). The effect of gene interactions on
the long-term response to selection. PNAS. National Academy of Sciences.
https://doi.org/10.1073/pnas.1518830113
chicago: Paixao, Tiago, and Nicholas H Barton. “The Effect of Gene Interactions
on the Long-Term Response to Selection.” PNAS. National Academy of Sciences,
2016. https://doi.org/10.1073/pnas.1518830113.
ieee: T. Paixao and N. H. Barton, “The effect of gene interactions on the long-term
response to selection,” PNAS, vol. 113, no. 16. National Academy of Sciences,
pp. 4422–4427, 2016.
ista: Paixao T, Barton NH. 2016. The effect of gene interactions on the long-term
response to selection. PNAS. 113(16), 4422–4427.
mla: Paixao, Tiago, and Nicholas H. Barton. “The Effect of Gene Interactions on
the Long-Term Response to Selection.” PNAS, vol. 113, no. 16, National
Academy of Sciences, 2016, pp. 4422–27, doi:10.1073/pnas.1518830113.
short: T. Paixao, N.H. Barton, PNAS 113 (2016) 4422–4427.
date_created: 2018-12-11T11:51:34Z
date_published: 2016-04-19T00:00:00Z
date_updated: 2021-01-12T06:50:08Z
day: '19'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1073/pnas.1518830113
ec_funded: 1
external_id:
pmid:
- '27044080'
intvolume: ' 113'
issue: '16'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843425/
month: '04'
oa: 1
oa_version: Published Version
page: 4422 - 4427
pmid: 1
project:
- _id: 25B07788-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '250152'
name: Limits to selection in biology and in evolutionary computation
- _id: 25B1EC9E-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618091'
name: Speed of Adaptation in Population Genetics and Evolutionary Computation
publication: PNAS
publication_status: published
publisher: National Academy of Sciences
publist_id: '5886'
quality_controlled: '1'
scopus_import: 1
status: public
title: The effect of gene interactions on the long-term response to selection
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 113
year: '2016'
...
---
_id: '1427'
abstract:
- lang: eng
text: Changes in gene expression are an important mode of evolution; however, the
proximate mechanism of these changes is poorly understood. In particular, little
is known about the effects of mutations within cis binding sites for transcription
factors, or the nature of epistatic interactions between these mutations. Here,
we tested the effects of single and double mutants in two cis binding sites involved
in the transcriptional regulation of the Escherichia coli araBAD operon, a component
of arabinose metabolism, using a synthetic system. This system decouples transcriptional
control from any posttranslational effects on fitness, allowing a precise estimate
of the effect of single and double mutations, and hence epistasis, on gene expression.
We found that epistatic interactions between mutations in the araBAD cis-regulatory
element are common, and that the predominant form of epistasis is negative. The
magnitude of the interactions depended on whether the mutations are located in
the same or in different operator sites. Importantly, these epistatic interactions
were dependent on the presence of arabinose, a native inducer of the araBAD operon
in vivo, with some interactions changing in sign (e.g., from negative to positive)
in its presence. This study thus reveals that mutations in even relatively simple
cis-regulatory elements interact in complex ways such that selection on the level
of gene expression in one environment might perturb regulation in the other environment
in an unpredictable and uncorrelated manner.
author:
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
- first_name: Anaisa
full_name: Moreno, Anaisa
last_name: Moreno
- 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: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
citation:
ama: Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. Epistatic interactions
in the arabinose cis-regulatory element. Molecular Biology and Evolution.
2016;33(3):761-769. doi:10.1093/molbev/msv269
apa: Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016).
Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology
and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269
chicago: Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan
P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.”
Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv269.
ieee: M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic
interactions in the arabinose cis-regulatory element,” Molecular Biology and
Evolution, vol. 33, no. 3. Oxford University Press, pp. 761–769, 2016.
ista: Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. 2016. Epistatic interactions
in the arabinose cis-regulatory element. Molecular Biology and Evolution. 33(3),
761–769.
mla: Lagator, Mato, et al. “Epistatic Interactions in the Arabinose Cis-Regulatory
Element.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University
Press, 2016, pp. 761–69, doi:10.1093/molbev/msv269.
short: M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology
and Evolution 33 (2016) 761–769.
date_created: 2018-12-11T11:51:57Z
date_published: 2016-03-01T00:00:00Z
date_updated: 2021-01-12T06:50:39Z
day: '01'
ddc:
- '570'
- '576'
department:
- _id: CaGu
- _id: JoBo
doi: 10.1093/molbev/msv269
ec_funded: 1
file:
- access_level: open_access
checksum: 1f456ce1d2aa2f67176a1709f9702ecf
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:09:27Z
date_updated: 2020-07-14T12:44:53Z
file_id: '4751'
file_name: IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf
file_size: 648115
relation: main_file
file_date_updated: 2020-07-14T12:44:53Z
has_accepted_license: '1'
intvolume: ' 33'
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 761 - 769
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Molecular Biology and Evolution
publication_status: published
publisher: Oxford University Press
publist_id: '5772'
pubrep_id: '588'
quality_controlled: '1'
scopus_import: 1
status: public
title: Epistatic interactions in the arabinose 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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 33
year: '2016'
...