---
_id: '7675'
abstract:
- lang: eng
text: 'In prokaryotes, thermodynamic models of gene regulation provide a highly
quantitative mapping from promoter sequences to gene expression levels that is
compatible with in vivo and in vitro bio-physical measurements. Such concordance
has not been achieved for models of enhancer function in eukaryotes. In equilibrium
models, it is difficult to reconcile the reported short transcription factor (TF)
residence times on the DNA with the high specificity of regulation. In non-equilibrium
models, progress is difficult due to an explosion in the number of parameters.
Here, we navigate this complexity by looking for minimal non-equilibrium enhancer
models that yield desired regulatory phenotypes: low TF residence time, high specificity
and tunable cooperativity. We find that a single extra parameter, interpretable
as the “linking rate” by which bound TFs interact with Mediator components, enables
our models to escape equilibrium bounds and access optimal regulatory phenotypes,
while remaining consistent with the reported phenomenology and simple enough to
be inferred from upcoming experiments. We further find that high specificity in
non-equilibrium models is in a tradeoff with gene expression noise, predicting
bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription.
By drastically reducing the vast parameter space to a much smaller subspace that
optimally realizes biological function prior to inference from data, our normative
approach holds promise for mathematical models in systems biology.'
article_processing_charge: No
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Benjamin
full_name: Zoller, Benjamin
last_name: Zoller
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Grah R, Zoller B, Tkačik G. Normative models of enhancer function. bioRxiv.
2020. doi:10.1101/2020.04.08.029405
apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Normative models of enhancer
function. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.08.029405
chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer
Function.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.08.029405.
ieee: R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,”
bioRxiv. Cold Spring Harbor Laboratory, 2020.
ista: Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv,
10.1101/2020.04.08.029405.
mla: Grah, Rok, et al. “Normative Models of Enhancer Function.” BioRxiv,
Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.08.029405.
short: R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020).
corr_author: '1'
date_created: 2020-04-23T10:12:51Z
date_published: 2020-04-09T00:00:00Z
date_updated: 2026-04-08T07:25:08Z
day: '09'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1101/2020.04.08.029405
language:
- iso: eng
main_file_link:
- open_access: '1'
url: 'https://doi.org/10.1101/2020.04.08.029405 '
month: '04'
oa: 1
oa_version: Preprint
project:
- _id: 2665AAFE-B435-11E9-9278-68D0E5697425
grant_number: RGP0034/2018
name: Can evolution minimize spurious signaling crosstalk to reach optimal performance?
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication: bioRxiv
publication_status: published
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '8155'
relation: dissertation_contains
status: public
status: public
title: Normative models of enhancer function
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8173'
abstract:
- lang: eng
text: Understanding how the activity of membrane receptors and cellular signaling
pathways shapes cell behavior is of fundamental interest in basic and applied
research. Reengineering receptors to react to light instead of their cognate ligands
allows for generating defined signaling inputs with high spatial and temporal
precision and facilitates the dissection of complex signaling networks. Here,
we describe fundamental considerations in the design of light-regulated receptor
tyrosine kinases (Opto-RTKs) and appropriate control experiments. We also introduce
methods for transient receptor expression in HEK293 cells, quantitative assessment
of signaling activity in reporter gene assays, semiquantitative assessment of
(in)activation time courses through Western blot (WB) analysis, and easy to implement
light stimulation hardware.
alternative_title:
- Methods in Molecular Biology
article_processing_charge: No
author:
- first_name: Stephanie
full_name: Kainrath, Stephanie
id: 32CFBA64-F248-11E8-B48F-1D18A9856A87
last_name: Kainrath
orcid: 0000-0002-6709-2195
- 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, Janovjak HL. Design and application of light-regulated receptor
tyrosine kinases. In: Niopek D, ed. Photoswitching Proteins. Vol 2173.
MIMB. Springer Nature; 2020:233-246. doi:10.1007/978-1-0716-0755-8_16'
apa: Kainrath, S., & Janovjak, H. L. (2020). Design and application of light-regulated
receptor tyrosine kinases. In D. Niopek (Ed.), Photoswitching Proteins
(Vol. 2173, pp. 233–246). Springer Nature. https://doi.org/10.1007/978-1-0716-0755-8_16
chicago: Kainrath, Stephanie, and Harald L Janovjak. “Design and Application of
Light-Regulated Receptor Tyrosine Kinases.” In Photoswitching Proteins,
edited by Dominik Niopek, 2173:233–46. MIMB. Springer Nature, 2020. https://doi.org/10.1007/978-1-0716-0755-8_16.
ieee: S. Kainrath and H. L. Janovjak, “Design and application of light-regulated
receptor tyrosine kinases,” in Photoswitching Proteins, vol. 2173, D. Niopek,
Ed. Springer Nature, 2020, pp. 233–246.
ista: 'Kainrath S, Janovjak HL. 2020.Design and application of light-regulated receptor
tyrosine kinases. In: Photoswitching Proteins. Methods in Molecular Biology, vol.
2173, 233–246.'
mla: Kainrath, Stephanie, and Harald L. Janovjak. “Design and Application of Light-Regulated
Receptor Tyrosine Kinases.” Photoswitching Proteins, edited by Dominik
Niopek, vol. 2173, Springer Nature, 2020, pp. 233–46, doi:10.1007/978-1-0716-0755-8_16.
short: S. Kainrath, H.L. Janovjak, in:, D. Niopek (Ed.), Photoswitching Proteins,
Springer Nature, 2020, pp. 233–246.
date_created: 2020-07-26T22:01:03Z
date_published: 2020-07-11T00:00:00Z
date_updated: 2026-04-16T09:22:45Z
day: '11'
department:
- _id: CaGu
doi: 10.1007/978-1-0716-0755-8_16
editor:
- first_name: Dominik
full_name: Niopek, Dominik
last_name: Niopek
external_id:
pmid:
- '32651922'
intvolume: ' 2173'
language:
- iso: eng
month: '07'
oa_version: None
page: 233-246
pmid: 1
publication: Photoswitching Proteins
publication_identifier:
eisbn:
- '9781071607558'
eissn:
- 1940-6029
isbn:
- '9781071607541'
issn:
- 1064-3745
publication_status: published
publisher: Springer Nature
scopus_import: '1'
series_title: MIMB
status: public
title: Design and application of light-regulated receptor tyrosine kinases
type: book_chapter
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 2173
year: '2020'
...
---
_id: '7680'
abstract:
- lang: eng
text: "Proteins and their complex dynamic interactions regulate cellular mechanisms
from sensing and transducing extracellular signals, to mediating genetic responses,
and sustaining or changing cell morphology. To manipulate these protein-protein
interactions (PPIs) that govern the behavior and fate of cells, synthetically
constructed, genetically encoded tools provide the means to precisely target proteins
of interest (POIs), and control their subcellular localization and activity in
vitro and in vivo. Ideal synthetic tools react to an orthogonal cue, i.e. a trigger
that does not activate any other endogenous process, thereby allowing manipulation
of the POI alone.\r\nIn optogenetics, naturally occurring photosensory domain
from plants, algae and bacteria are re-purposed and genetically fused to POIs.
Illumination with light of a specific wavelength triggers a conformational change
that can mediate PPIs, such as dimerization or oligomerization. By using light
as a trigger, these tools can be activated with high spatial and temporal precision,
on subcellular and millisecond scales. Chemogenetic tools consist of protein domains
that recognize and bind small molecules. By genetic fusion to POIs, these domains
can mediate PPIs upon addition of their specific ligands, which are often synthetically
designed to provide highly specific interactions and exhibit good bioavailability.\r\nMost
optogenetic tools to mediate PPIs are based on well-studied photoreceptors responding
to red, blue or near-UV light, leaving a striking gap in the green band of the
visible light spectrum. Among both optogenetic and chemogenetic tools, there is
an abundance of methods to induce PPIs, but tools to disrupt them require UV illumination,
rely on covalent linkage and subsequent enzymatic cleavage or initially result
in protein clustering of unknown stoichiometry.\r\nThis work describes how the
recently structurally and photochemically characterized green-light responsive
cobalamin-binding domains (CBDs) from bacterial transcription factors were re-purposed
to function as a green-light responsive optogenetic tool. In contrast to previously
engineered optogenetic tools, CBDs do not induce PPI, but rather confer a PPI
already upon expression, which can be rapidly disrupted by illumination. This
was employed to mimic inhibition of constitutive activity of a growth factor receptor,
and successfully implement for cell signalling in mammalian cells and in vivo
to rescue development in zebrafish. This work further describes the development
and application of a chemically induced de-dimerizer (CDD) based on a recently
identified and structurally described bacterial oxyreductase. CDD forms a dimer
upon expression in absence of its cofactor, the flavin derivative F420. Safety
and of domain expression and ligand exposure are demonstrated in vitro and in
vivo in zebrafish. The system is further applied to inhibit cell signalling output
from a chimeric receptor upon F420 treatment.\r\nCBDs and CDD expand the repertoire
of synthetic tools by providing novel mechanisms of mediating PPIs, and by recognizing
previously not utilized cues. In the future, they can readily be combined with
existing synthetic tools to functionally manipulate PPIs in vitro and in vivo."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Stephanie
full_name: Kainrath, Stephanie
id: 32CFBA64-F248-11E8-B48F-1D18A9856A87
last_name: Kainrath
orcid: 0000-0002-6709-2195
citation:
ama: Kainrath S. Synthetic tools for optogenetic and chemogenetic inhibition of
cellular signals. 2020. doi:10.15479/AT:ISTA:7680
apa: Kainrath, S. (2020). Synthetic tools for optogenetic and chemogenetic inhibition
of cellular signals. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7680
chicago: Kainrath, Stephanie. “Synthetic Tools for Optogenetic and Chemogenetic
Inhibition of Cellular Signals.” Institute of Science and Technology Austria,
2020. https://doi.org/10.15479/AT:ISTA:7680.
ieee: S. Kainrath, “Synthetic tools for optogenetic and chemogenetic inhibition
of cellular signals,” Institute of Science and Technology Austria, 2020.
ista: Kainrath S. 2020. Synthetic tools for optogenetic and chemogenetic inhibition
of cellular signals. Institute of Science and Technology Austria.
mla: Kainrath, Stephanie. Synthetic Tools for Optogenetic and Chemogenetic Inhibition
of Cellular Signals. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7680.
short: S. Kainrath, Synthetic Tools for Optogenetic and Chemogenetic Inhibition
of Cellular Signals, Institute of Science and Technology Austria, 2020.
corr_author: '1'
date_created: 2020-04-24T16:00:51Z
date_published: 2020-04-24T00:00:00Z
date_updated: 2025-11-03T23:30:47Z
day: '24'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:7680
file:
- access_level: open_access
checksum: fb9a4468eb27be92690728e35c823796
content_type: application/pdf
creator: stgingl
date_created: 2020-04-28T11:19:21Z
date_updated: 2021-10-31T23:30:05Z
embargo: 2021-10-30
file_id: '7692'
file_name: Thesis_without-signatures_PDFA.pdf
file_size: 3268017
relation: main_file
- access_level: closed
checksum: f6c80ca97104a631a328cb79a2c53493
content_type: application/octet-stream
creator: stgingl
date_created: 2020-04-28T11:19:24Z
date_updated: 2021-10-31T23:30:05Z
embargo_to: open_access
file_id: '7693'
file_name: Thesis_without signatures.docx
file_size: 5167703
relation: source_file
file_date_updated: 2021-10-31T23:30:05Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: None
page: '98'
publication_identifier:
eissn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '1028'
relation: dissertation_contains
status: public
status: public
supervisor:
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
title: Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals
type: dissertation
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '7652'
abstract:
- lang: eng
text: Organisms cope with change by taking advantage of transcriptional regulators.
However, when faced with rare environments, the evolution of transcriptional regulators
and their promoters may be too slow. Here, we investigate whether the intrinsic
instability of gene duplication and amplification provides a generic alternative
to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations
in Escherichia coli, we show that gene duplications and amplifications enable
adaptation to fluctuating environments by rapidly generating copy-number and,
therefore, expression-level polymorphisms. This amplification-mediated gene expression
tuning (AMGET) occurs on timescales that are similar to canonical gene regulation
and can respond to rapid environmental changes. Mathematical modelling shows that
amplifications also tune gene expression in stochastic environments in which transcription-factor-based
schemes are hard to evolve or maintain. The fleeting nature of gene amplifications
gives rise to a generic population-level mechanism that relies on genetic heterogeneity
to rapidly tune the expression of any gene, without leaving any genomic signature.
acknowledgement: We thank L. Hurst, N. Barton, M. Pleska, M. Steinrück, B. Kavcic
and A. Staron for input on the manuscript, and To. Bergmiller and R. Chait for help
with microfluidics experiments. I.T. is a recipient the OMV fellowship. R.G. is
a recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences)
Fellowship of the Austrian Academy of Sciences.
article_processing_charge: No
article_type: original
author:
- first_name: Isabella
full_name: Tomanek, Isabella
id: 3981F020-F248-11E8-B48F-1D18A9856A87
last_name: Tomanek
orcid: 0000-0001-6197-363X
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: M.
full_name: Lagator, M.
last_name: Lagator
- first_name: A. M. C.
full_name: Andersson, A. M. C.
last_name: Andersson
- 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: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
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: Tomanek I, Grah R, Lagator M, et al. Gene amplification as a form of population-level
gene expression regulation. Nature Ecology & Evolution. 2020;4(4):612-625.
doi:10.1038/s41559-020-1132-7
apa: Tomanek, I., Grah, R., Lagator, M., Andersson, A. M. C., Bollback, J. P., Tkačik,
G., & Guet, C. C. (2020). Gene amplification as a form of population-level
gene expression regulation. Nature Ecology & Evolution. Springer Nature.
https://doi.org/10.1038/s41559-020-1132-7
chicago: Tomanek, Isabella, Rok Grah, M. Lagator, A. M. C. Andersson, Jonathan P
Bollback, Gašper Tkačik, and Calin C Guet. “Gene Amplification as a Form of Population-Level
Gene Expression Regulation.” Nature Ecology & Evolution. Springer Nature,
2020. https://doi.org/10.1038/s41559-020-1132-7.
ieee: I. Tomanek et al., “Gene amplification as a form of population-level
gene expression regulation,” Nature Ecology & Evolution, vol. 4, no.
4. Springer Nature, pp. 612–625, 2020.
ista: Tomanek I, Grah R, Lagator M, Andersson AMC, Bollback JP, Tkačik G, Guet CC.
2020. Gene amplification as a form of population-level gene expression regulation.
Nature Ecology & Evolution. 4(4), 612–625.
mla: Tomanek, Isabella, et al. “Gene Amplification as a Form of Population-Level
Gene Expression Regulation.” Nature Ecology & Evolution, vol. 4, no.
4, Springer Nature, 2020, pp. 612–25, doi:10.1038/s41559-020-1132-7.
short: I. Tomanek, R. Grah, M. Lagator, A.M.C. Andersson, J.P. Bollback, G. Tkačik,
C.C. Guet, Nature Ecology & Evolution 4 (2020) 612–625.
date_created: 2020-04-08T15:20:53Z
date_published: 2020-04-01T00:00:00Z
date_updated: 2026-04-27T22:30:46Z
day: '01'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.1038/s41559-020-1132-7
external_id:
isi:
- '000519008300005'
pmid:
- '32152532'
file:
- access_level: open_access
checksum: ef3bbf42023e30b2c24a6278025d2040
content_type: application/pdf
creator: dernst
date_created: 2020-10-09T09:56:01Z
date_updated: 2020-10-09T09:56:01Z
file_id: '8640'
file_name: 2020_NatureEcolEvo_Tomanek.pdf
file_size: 745242
relation: main_file
success: 1
file_date_updated: 2020-10-09T09:56:01Z
has_accepted_license: '1'
intvolume: ' 4'
isi: 1
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Submitted Version
page: 612-625
pmid: 1
project:
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication: Nature Ecology & Evolution
publication_identifier:
issn:
- 2397-334X
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/
record:
- id: '7016'
relation: research_data
status: public
- id: '7383'
relation: research_data
status: public
- id: '8155'
relation: dissertation_contains
status: public
- id: '8653'
relation: used_in_publication
status: public
scopus_import: '1'
status: public
title: Gene amplification as a form of population-level gene expression regulation
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 4
year: '2020'
...
---
OA_place: publisher
_id: '8653'
abstract:
- lang: eng
text: "Mutations are the raw material of evolution and come in many different flavors.
Point mutations change a single letter in the DNA sequence, while copy number
mutations like duplications or deletions add or remove many letters of the DNA
sequence simultaneously. Each type of mutation exhibits specific properties like
its rate of formation and reversal. \r\nGene expression is a fundamental phenotype
that can be altered by both, point and copy number mutations. The following thesis
is concerned with the dynamics of gene expression evolution and how it is affected
by the properties exhibited by point and copy number mutations. Specifically,
we are considering i) copy number mutations during adaptation to fluctuating environments
and ii) the interaction of copy number and point mutations during adaptation to
constant environments. "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Isabella
full_name: Tomanek, Isabella
id: 3981F020-F248-11E8-B48F-1D18A9856A87
last_name: Tomanek
orcid: 0000-0001-6197-363X
citation:
ama: Tomanek I. The evolution of gene expression by copy number and point mutations.
2020. doi:10.15479/AT:ISTA:8653
apa: Tomanek, I. (2020). The evolution of gene expression by copy number and
point mutations. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8653
chicago: Tomanek, Isabella. “The Evolution of Gene Expression by Copy Number and
Point Mutations.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8653.
ieee: I. Tomanek, “The evolution of gene expression by copy number and point mutations,”
Institute of Science and Technology Austria, 2020.
ista: Tomanek I. 2020. The evolution of gene expression by copy number and point
mutations. Institute of Science and Technology Austria.
mla: Tomanek, Isabella. The Evolution of Gene Expression by Copy Number and Point
Mutations. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8653.
short: I. Tomanek, The Evolution of Gene Expression by Copy Number and Point Mutations,
Institute of Science and Technology Austria, 2020.
corr_author: '1'
date_created: 2020-10-13T13:02:33Z
date_published: 2020-10-13T00:00:00Z
date_updated: 2026-04-08T07:29:19Z
day: '13'
ddc:
- '576'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:8653
file:
- access_level: closed
checksum: c01d9f59794b4b70528f37637c17ad02
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: itomanek
date_created: 2020-10-16T12:14:21Z
date_updated: 2021-10-20T22:30:03Z
embargo_to: open_access
file_id: '8666'
file_name: Thesis_ITomanek_final_201016.docx
file_size: 25131884
relation: source_file
- access_level: open_access
checksum: f8edbc3b0f81a780e13ca1e561d42d8b
content_type: application/pdf
creator: itomanek
date_created: 2020-10-16T12:14:21Z
date_updated: 2021-10-20T22:30:03Z
embargo: 2021-10-19
file_id: '8667'
file_name: Thesis_ITomanek_final_201016.pdf
file_size: 15405675
relation: main_file
file_date_updated: 2021-10-20T22:30:03Z
has_accepted_license: '1'
keyword:
- duplication
- amplification
- promoter
- CNV
- AMGET
- experimental evolution
- Escherichia coli
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '117'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7652'
relation: research_data
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 evolution of gene expression by copy number and point mutations
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2020'
...
---
_id: '138'
abstract:
- lang: eng
text: Autoregulation is the direct modulation of gene expression by the product
of the corresponding gene. Autoregulation of bacterial gene expression has been
mostly studied at the transcriptional level, when a protein acts as the cognate
transcriptional repressor. A recent study investigating dynamics of the bacterial
toxin–antitoxin MazEF system has shown how autoregulation at both the transcriptional
and post-transcriptional levels affects the heterogeneity of Escherichia coli
populations. Toxin–antitoxin systems hold a crucial but still elusive part in
bacterial response to stress. This perspective highlights how these modules can
also serve as a great model system for investigating basic concepts in gene regulation.
However, as the genomic background and environmental conditions substantially
influence toxin activation, it is important to study (auto)regulation of toxin–antitoxin
systems in well-defined setups as well as in conditions that resemble the environmental
niche.
article_processing_charge: Yes (via OA deal)
author:
- first_name: Nela
full_name: Nikolic, Nela
id: 42D9CABC-F248-11E8-B48F-1D18A9856A87
last_name: Nikolic
orcid: 0000-0001-9068-6090
citation:
ama: 'Nikolic N. Autoregulation of bacterial gene expression: lessons from the MazEF
toxin–antitoxin system. Current Genetics. 2019;65(1):133-138. doi:10.1007/s00294-018-0879-8'
apa: 'Nikolic, N. (2019). Autoregulation of bacterial gene expression: lessons from
the MazEF toxin–antitoxin system. Current Genetics. Springer. https://doi.org/10.1007/s00294-018-0879-8'
chicago: 'Nikolic, Nela. “Autoregulation of Bacterial Gene Expression: Lessons from
the MazEF Toxin–Antitoxin System.” Current Genetics. Springer, 2019. https://doi.org/10.1007/s00294-018-0879-8.'
ieee: 'N. Nikolic, “Autoregulation of bacterial gene expression: lessons from the
MazEF toxin–antitoxin system,” Current Genetics, vol. 65, no. 1. Springer,
pp. 133–138, 2019.'
ista: 'Nikolic N. 2019. Autoregulation of bacterial gene expression: lessons from
the MazEF toxin–antitoxin system. Current Genetics. 65(1), 133–138.'
mla: 'Nikolic, Nela. “Autoregulation of Bacterial Gene Expression: Lessons from
the MazEF Toxin–Antitoxin System.” Current Genetics, vol. 65, no. 1, Springer,
2019, pp. 133–38, doi:10.1007/s00294-018-0879-8.'
short: N. Nikolic, Current Genetics 65 (2019) 133–138.
date_created: 2018-12-11T11:44:50Z
date_published: 2019-02-01T00:00:00Z
date_updated: 2025-04-15T06:50:19Z
day: '01'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1007/s00294-018-0879-8
ec_funded: 1
external_id:
isi:
- '000456958800017'
file:
- access_level: open_access
checksum: 6779708b0b632a1a6ed28c56f5161142
content_type: application/pdf
creator: dernst
date_created: 2019-02-06T07:50:58Z
date_updated: 2020-07-14T12:44:47Z
file_id: '5930'
file_name: 2019_CurrentGenetics_Nikolic.pdf
file_size: 776399
relation: main_file
file_date_updated: 2020-07-14T12:44:47Z
has_accepted_license: '1'
intvolume: ' 65'
isi: 1
issue: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '02'
oa: 1
oa_version: Published Version
page: 133-138
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Current Genetics
publication_status: published
publisher: Springer
publist_id: '7785'
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin
system'
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: 65
year: '2019'
...
---
_id: '196'
abstract:
- lang: eng
text: 'The abelian sandpile serves as a model to study self-organized criticality,
a phenomenon occurring in biological, physical and social processes. The identity
of the abelian group is a fractal composed of self-similar patches, and its limit
is subject of extensive collaborative research. Here, we analyze the evolution
of the sandpile identity under harmonic fields of different orders. We show that
this evolution corresponds to periodic cycles through the abelian group characterized
by the smooth transformation and apparent conservation of the patches constituting
the identity. The dynamics induced by second and third order harmonics resemble
smooth stretchings, respectively translations, of the identity, while the ones
induced by fourth order harmonics resemble magnifications and rotations. Starting
with order three, the dynamics pass through extended regions of seemingly random
configurations which spontaneously reassemble into accentuated patterns. We show
that the space of harmonic functions projects to the extended analogue of the
sandpile group, thus providing a set of universal coordinates identifying configurations
between different domains. Since the original sandpile group is a subgroup of
the extended one, this directly implies that it admits a natural renormalization.
Furthermore, we show that the harmonic fields can be induced by simple Markov
processes, and that the corresponding stochastic dynamics show remarkable robustness
over hundreds of periods. Finally, we encode information into seemingly random
configurations, and decode this information with an algorithm requiring minimal
prior knowledge. Our results suggest that harmonic fields might split the sandpile
group into sub-sets showing different critical coefficients, and that it might
be possible to extend the fractal structure of the identity beyond the boundaries
of its domain. '
acknowledgement: "M.L. is grateful to the members of the C Guet and G Tkacik groups
for valuable comments and support. M.S. is grateful to Nikita Kalinin for inspiring
communications.\r\n"
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Mikhail
full_name: Shkolnikov, Mikhail
id: 35084A62-F248-11E8-B48F-1D18A9856A87
last_name: Shkolnikov
orcid: 0000-0002-4310-178X
citation:
ama: Lang M, Shkolnikov M. Harmonic dynamics of the Abelian sandpile. Proceedings
of the National Academy of Sciences of the United States of America. 2019;116(8):2821-2830.
doi:10.1073/pnas.1812015116
apa: Lang, M., & Shkolnikov, M. (2019). Harmonic dynamics of the Abelian sandpile.
Proceedings of the National Academy of Sciences of the United States of America.
National Academy of Sciences. https://doi.org/10.1073/pnas.1812015116
chicago: Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian
Sandpile.” Proceedings of the National Academy of Sciences of the United States
of America. National Academy of Sciences, 2019. https://doi.org/10.1073/pnas.1812015116.
ieee: M. Lang and M. Shkolnikov, “Harmonic dynamics of the Abelian sandpile,” Proceedings
of the National Academy of Sciences of the United States of America, vol.
116, no. 8. National Academy of Sciences, pp. 2821–2830, 2019.
ista: Lang M, Shkolnikov M. 2019. Harmonic dynamics of the Abelian sandpile. Proceedings
of the National Academy of Sciences of the United States of America. 116(8), 2821–2830.
mla: Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.”
Proceedings of the National Academy of Sciences of the United States of America,
vol. 116, no. 8, National Academy of Sciences, 2019, pp. 2821–30, doi:10.1073/pnas.1812015116.
short: M. Lang, M. Shkolnikov, Proceedings of the National Academy of Sciences of
the United States of America 116 (2019) 2821–2830.
corr_author: '1'
date_created: 2018-12-11T11:45:08Z
date_published: 2019-02-19T00:00:00Z
date_updated: 2025-06-03T11:18:16Z
day: '19'
department:
- _id: CaGu
- _id: GaTk
- _id: TaHa
doi: 10.1073/pnas.1812015116
external_id:
arxiv:
- '1806.10823'
isi:
- '000459074400013'
pmid:
- ' 30728300'
intvolume: ' 116'
isi: 1
issue: '8'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1073/pnas.1812015116
month: '02'
oa: 1
oa_version: Published Version
page: 2821-2830
pmid: 1
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- 1091-6490
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on IST Webpage
relation: press_release
url: https://ist.ac.at/en/news/famous-sandpile-model-shown-to-move-like-a-traveling-sand-dune/
scopus_import: '1'
status: public
title: Harmonic dynamics of the Abelian sandpile
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 116
year: '2019'
...
---
_id: '9786'
article_processing_charge: No
author:
- first_name: Jakob
full_name: Ruess, Jakob
id: 4A245D00-F248-11E8-B48F-1D18A9856A87
last_name: Ruess
orcid: 0000-0003-1615-3282
- 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
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Ruess J, Pleska M, Guet CC, Tkačik G. Supporting text and results. 2019. doi:10.1371/journal.pcbi.1007168.s001
apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Supporting text
and results. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168.s001
chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Supporting
Text and Results.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.s001.
ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Supporting text and results.”
Public Library of Science, 2019.
ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Supporting text and results, Public
Library of Science, 10.1371/journal.pcbi.1007168.s001.
mla: Ruess, Jakob, et al. Supporting Text and Results. Public Library of
Science, 2019, doi:10.1371/journal.pcbi.1007168.s001.
short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019).
date_created: 2021-08-06T08:23:43Z
date_published: 2019-07-02T00:00:00Z
date_updated: 2025-04-15T07:33:55Z
day: '02'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007168.s001
month: '07'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '6784'
relation: used_in_publication
status: public
status: public
title: Supporting text and results
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2019'
...
---
_id: '6717'
abstract:
- lang: eng
text: With the recent publication by Silpe and Bassler (2019), considering phage
detection of a bacterial quorum-sensing (QS) autoinducer, we now have as many
as five examples of phage-associated intercellular communication (Table 1). Each
potentially involves ecological inferences by phages as to concentrations of surrounding
phage-infected or uninfected bacteria. While the utility of phage detection of
bacterial QS molecules may at first glance appear to be straightforward, we suggest
in this commentary that the underlying ecological explanation is unlikely to be
simple.
article_number: '1171'
article_processing_charge: Yes (via OA deal)
author:
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
- first_name: Stephen T.
full_name: Abedon, Stephen T.
last_name: Abedon
citation:
ama: 'Igler C, Abedon ST. Commentary: A host-produced quorum-sensing autoinducer
controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 2019;10.
doi:10.3389/fmicb.2019.01171'
apa: 'Igler, C., & Abedon, S. T. (2019). Commentary: A host-produced quorum-sensing
autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology.
Frontiers. https://doi.org/10.3389/fmicb.2019.01171'
chicago: 'Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing
Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology.
Frontiers, 2019. https://doi.org/10.3389/fmicb.2019.01171.'
ieee: 'C. Igler and S. T. Abedon, “Commentary: A host-produced quorum-sensing autoinducer
controls a phage lysis-lysogeny decision,” Frontiers in Microbiology, vol.
10. Frontiers, 2019.'
ista: 'Igler C, Abedon ST. 2019. Commentary: A host-produced quorum-sensing autoinducer
controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 10, 1171.'
mla: 'Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing
Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology,
vol. 10, 1171, Frontiers, 2019, doi:10.3389/fmicb.2019.01171.'
short: C. Igler, S.T. Abedon, Frontiers in Microbiology 10 (2019).
date_created: 2019-07-28T21:59:18Z
date_published: 2019-06-03T00:00:00Z
date_updated: 2025-04-14T13:38:17Z
day: '03'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.3389/fmicb.2019.01171
external_id:
isi:
- '000470131200001'
file:
- access_level: open_access
checksum: 317a06067e9a8e717bb55f23e0d77ba7
content_type: application/pdf
creator: apreinsp
date_created: 2019-07-29T07:51:54Z
date_updated: 2020-07-14T12:47:38Z
file_id: '6722'
file_name: 2019_Frontiers_Igler.pdf
file_size: 246151
relation: main_file
file_date_updated: 2020-07-14T12:47:38Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
project:
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
grant_number: '24573'
name: Design principles underlying genetic switch architecture
publication: Frontiers in Microbiology
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny
decision'
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2019'
...
---
_id: '6784'
abstract:
- lang: eng
text: Mathematical models have been used successfully at diverse scales of biological
organization, ranging from ecology and population dynamics to stochastic reaction
events occurring between individual molecules in single cells. Generally, many
biological processes unfold across multiple scales, with mutations being the best
studied example of how stochasticity at the molecular scale can influence outcomes
at the population scale. In many other contexts, however, an analogous link between
micro- and macro-scale remains elusive, primarily due to the challenges involved
in setting up and analyzing multi-scale models. Here, we employ such a model to
investigate how stochasticity propagates from individual biochemical reaction
events in the bacterial innate immune system to the ecology of bacteria and bacterial
viruses. We show analytically how the dynamics of bacterial populations are shaped
by the activities of immunity-conferring enzymes in single cells and how the ecological
consequences imply optimal bacterial defense strategies against viruses. Our results
suggest that bacterial populations in the presence of viruses can either optimize
their initial growth rate or their population size, with the first strategy favoring
simple immunity featuring a single restriction modification system and the second
strategy favoring complex bacterial innate immunity featuring several simultaneously
active restriction modification systems.
article_number: e1007168
article_processing_charge: No
article_type: original
author:
- first_name: Jakob
full_name: Ruess, Jakob
id: 4A245D00-F248-11E8-B48F-1D18A9856A87
last_name: Ruess
orcid: 0000-0003-1615-3282
- 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
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Ruess J, Pleska M, Guet CC, Tkačik G. Molecular noise of innate immunity shapes
bacteria-phage ecologies. PLoS Computational Biology. 2019;15(7). doi:10.1371/journal.pcbi.1007168
apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Molecular noise
of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology.
Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168
chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Molecular
Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational
Biology. Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.
ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Molecular noise of innate
immunity shapes bacteria-phage ecologies,” PLoS Computational Biology,
vol. 15, no. 7. Public Library of Science, 2019.
ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Molecular noise of innate immunity
shapes bacteria-phage ecologies. PLoS Computational Biology. 15(7), e1007168.
mla: Ruess, Jakob, et al. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage
Ecologies.” PLoS Computational Biology, vol. 15, no. 7, e1007168, Public
Library of Science, 2019, doi:10.1371/journal.pcbi.1007168.
short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15
(2019).
date_created: 2019-08-11T21:59:19Z
date_published: 2019-07-02T00:00:00Z
date_updated: 2025-04-14T13:46:26Z
day: '02'
ddc:
- '570'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007168
external_id:
isi:
- '000481577700032'
file:
- access_level: open_access
checksum: 7ded4721b41c2a0fc66a1c634540416a
content_type: application/pdf
creator: dernst
date_created: 2019-08-12T12:27:26Z
date_updated: 2020-07-14T12:47:40Z
file_id: '6803'
file_name: 2019_PlosComputBiology_Ruess.pdf
file_size: 2200003
relation: main_file
file_date_updated: 2020-07-14T12:47:40Z
has_accepted_license: '1'
intvolume: ' 15'
isi: 1
issue: '7'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
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
- _id: 251BCBEC-B435-11E9-9278-68D0E5697425
grant_number: RGY0079/2011
name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification
Systems
publication: PLoS Computational Biology
publication_identifier:
eissn:
- 1553-7358
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
record:
- id: '9786'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Molecular noise of innate immunity shapes bacteria-phage ecologies
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 15
year: '2019'
...
---
_id: '7016'
abstract:
- lang: eng
text: Organisms cope with change by employing transcriptional regulators. However,
when faced with rare environments, the evolution of transcriptional regulators
and their promoters may be too slow. We ask whether the intrinsic instability
of gene duplication and amplification provides a generic alternative to canonical
gene regulation. By real-time monitoring of gene copy number mutations in E. coli,
we show that gene duplications and amplifications enable adaptation to fluctuating
environments by rapidly generating copy number, and hence expression level, polymorphism.
This ‘amplification-mediated gene expression tuning’ occurs on timescales similar
to canonical gene regulation and can deal with rapid environmental changes. Mathematical
modeling shows that amplifications also tune gene expression in stochastic environments
where transcription factor-based schemes are hard to evolve or maintain. The fleeting
nature of gene amplifications gives rise to a generic population-level mechanism
that relies on genetic heterogeneity to rapidly tune expression of any gene, without
leaving any genomic signature.
article_processing_charge: No
author:
- first_name: Isabella
full_name: Tomanek, Isabella
id: 3981F020-F248-11E8-B48F-1D18A9856A87
last_name: Tomanek
orcid: 0000-0001-6197-363X
citation:
ama: Tomanek I. Data for the paper “Gene amplification as a form of population-level
gene expression regulation.” 2019. doi:10.15479/AT:ISTA:7016
apa: Tomanek, I. (2019). Data for the paper “Gene amplification as a form of population-level
gene expression regulation.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7016
chicago: Tomanek, Isabella. “Data for the Paper ‘Gene Amplification as a Form of
Population-Level Gene Expression Regulation.’” Institute of Science and Technology
Austria, 2019. https://doi.org/10.15479/AT:ISTA:7016.
ieee: I. Tomanek, “Data for the paper ‘Gene amplification as a form of population-level
gene expression regulation.’” Institute of Science and Technology Austria, 2019.
ista: Tomanek I. 2019. Data for the paper ‘Gene amplification as a form of population-level
gene expression regulation’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:7016.
mla: Tomanek, Isabella. Data for the Paper “Gene Amplification as a Form of Population-Level
Gene Expression Regulation.” Institute of Science and Technology Austria,
2019, doi:10.15479/AT:ISTA:7016.
short: I. Tomanek, (2019).
contributor:
- contributor_type: project_leader
first_name: Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
date_created: 2019-11-13T09:07:31Z
date_published: 2019-11-13T00:00:00Z
date_updated: 2025-06-12T07:34:12Z
day: '13'
ddc:
- '576'
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:7016
file:
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checksum: 72441055043eda4cbf1398a422e2c118
content_type: application/octet-stream
creator: itomanek
date_created: 2019-11-13T08:52:21Z
date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 1 - amplified.
file_id: '7017'
file_name: D8_S35_R2_001.fastq
file_size: 2456192500
relation: main_file
title: Locus1_amplified
- access_level: open_access
checksum: a4ac50bf655d9c751f0305ade5c2ee16
content_type: application/octet-stream
creator: itomanek
date_created: 2019-11-13T08:52:59Z
date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 1 - ancestral.
file_id: '7018'
file_name: IT028_S11_R2_001.fastq
file_size: 2833452234
relation: main_file
title: Locus1_ancestral
- access_level: open_access
checksum: 5b227708ff478ca06e3f0448a4efdc2f
content_type: application/octet-stream
creator: itomanek
date_created: 2019-11-13T08:54:10Z
date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 1 - amplified, after
DOG-selection.
file_id: '7019'
file_name: D8-DOG1_S47_R2_001.fastq
file_size: 2878017264
relation: main_file
title: Locus1_amplified_DOG
- access_level: open_access
checksum: d9550a4c044116075fa83f8f2ea31d6f
content_type: application/octet-stream
creator: itomanek
date_created: 2019-11-13T08:54:27Z
date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 2 - amplified.
file_id: '7020'
file_name: D4_S71_R2_001.fastq
file_size: 2180826995
relation: main_file
title: Locus2_amplified
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content_type: application/octet-stream
creator: itomanek
date_created: 2019-11-13T08:55:58Z
date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 2 - ancestral.
file_id: '7021'
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file_size: 2108826444
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title: Locus2_ancestral
- access_level: open_access
checksum: 8aeb1da771713c7baa5a847eff889604
content_type: application/octet-stream
creator: itomanek
date_created: 2019-11-21T12:31:01Z
date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 2 - amplified, after
DOG-selection.
file_id: '7092'
file_name: D4-DOG1_S83_R2_001.fastq
file_size: 3144330494
relation: main_file
title: Locus2_amplified_DOG
- access_level: open_access
checksum: bf7d4b053f14af4655fb5574209fdb2d
content_type: application/zip
creator: itomanek
date_created: 2020-01-14T11:22:27Z
date_updated: 2020-07-14T12:47:47Z
description: Compressed genbank file format containing the sequence of the chromosomal
reporter gene cassette.
file_id: '7273'
file_name: galK_dual_reporter_cassette.gb.zip
file_size: 4179
relation: main_file
title: DNA sequence of the chromosomal reporter gene cassette
- access_level: open_access
checksum: 5e91cee2eff6f4a7cde456c6fb07c2ff
content_type: text/plain
creator: dernst
date_created: 2020-01-15T14:15:55Z
date_updated: 2020-07-14T12:47:47Z
file_id: '7335'
file_name: Readme_7016.txt
file_size: 435
relation: main_file
title: Read_me_sequence_data
- access_level: open_access
checksum: 5e6745dcfb9c1b11dd935ac3ee45fe33
content_type: application/zip
creator: itomanek
date_created: 2020-01-22T15:44:16Z
date_updated: 2020-07-14T12:47:47Z
description: FACS data associated with Fig. 2c - see read_me_FACS
file_id: '7351'
file_name: FACS_data.xlsx.zip
file_size: 3765861
relation: main_file
title: FACS data
- access_level: open_access
checksum: a85caf092ae4b17668f70af2d93fad00
content_type: text/rtf
creator: itomanek
date_created: 2020-01-22T15:44:16Z
date_updated: 2020-07-14T12:47:47Z
file_id: '7352'
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file_size: 4996
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checksum: fd8ba5d75d24e47ddf7e70bfdadb40d4
content_type: text/rtf
creator: itomanek
date_created: 2020-01-22T15:44:16Z
date_updated: 2020-07-14T12:47:47Z
file_id: '7353'
file_name: read_me_microfluidics.rtf
file_size: 868
relation: main_file
- access_level: open_access
checksum: 69c5dc5ca5c069a138183c934acc1778
content_type: application/zip
creator: itomanek
date_created: 2020-01-22T15:44:17Z
date_updated: 2020-07-14T12:47:47Z
description: microfluidics time trace data - see read_me_microfluidics
file_id: '7354'
file_name: microfuidics_data.zip
file_size: 8141727
relation: main_file
title: microfluidics data
file_date_updated: 2020-07-14T12:47:47Z
has_accepted_license: '1'
keyword:
- Escherichia coli
- gene amplification
- galactose
- DOG
- experimental evolution
- Illumina sequence data
- FACS data
- microfluidics data
month: '11'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7652'
relation: used_in_publication
status: public
status: public
title: Data for the paper "Gene amplification as a form of population-level gene expression
regulation"
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2019'
...
---
_id: '6465'
abstract:
- lang: eng
text: Tight control over protein degradation is a fundamental requirement for cells
to respond rapidly to various stimuli and adapt to a fluctuating environment.
Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons)
for the precise regulation of protein expression profiles in mammalian cells by
modulating target protein half-lives in a predictable manner. Using the well-established
tetracycline gene-regulation system as a model, we show that the dynamics of protein
expression can be tuned by fusing appropriate degron tags to gene regulators.
Next, we apply this degron library to tune a synthetic pulse-generating circuit
in mammalian cells. With this toolbox we establish a set of pulse generators with
tailored pulse lengths and magnitudes of protein expression. This methodology
will prove useful in the functional roles of essential proteins, fine-tuning of
gene-expression systems, and enabling a higher complexity in the design of synthetic
biological systems in mammalian cells.
article_number: '2013'
article_processing_charge: No
author:
- first_name: Hélène
full_name: Chassin, Hélène
last_name: Chassin
- first_name: Marius
full_name: Müller, Marius
last_name: Müller
- first_name: Marcel
full_name: Tigges, Marcel
last_name: Tigges
- first_name: Leo
full_name: Scheller, Leo
last_name: Scheller
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Martin
full_name: Fussenegger, Martin
last_name: Fussenegger
citation:
ama: Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. A modular
degron library for synthetic circuits in mammalian cells. Nature Communications.
2019;10(1). doi:10.1038/s41467-019-09974-5
apa: Chassin, H., Müller, M., Tigges, M., Scheller, L., Lang, M., & Fussenegger,
M. (2019). A modular degron library for synthetic circuits in mammalian cells.
Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-09974-5
chicago: Chassin, Hélène, Marius Müller, Marcel Tigges, Leo Scheller, Moritz Lang,
and Martin Fussenegger. “A Modular Degron Library for Synthetic Circuits in Mammalian
Cells.” Nature Communications. Springer Nature, 2019. https://doi.org/10.1038/s41467-019-09974-5.
ieee: H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, and M. Fussenegger,
“A modular degron library for synthetic circuits in mammalian cells,” Nature
Communications, vol. 10, no. 1. Springer Nature, 2019.
ista: Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. 2019. A
modular degron library for synthetic circuits in mammalian cells. Nature Communications.
10(1), 2013.
mla: Chassin, Hélène, et al. “A Modular Degron Library for Synthetic Circuits in
Mammalian Cells.” Nature Communications, vol. 10, no. 1, 2013, Springer
Nature, 2019, doi:10.1038/s41467-019-09974-5.
short: H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, M. Fussenegger, Nature
Communications 10 (2019).
date_created: 2019-05-19T21:59:14Z
date_published: 2019-05-01T00:00:00Z
date_updated: 2026-04-02T11:48:53Z
day: '01'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1038/s41467-019-09974-5
external_id:
isi:
- '000466338600006'
file:
- access_level: open_access
checksum: e214d3e4f8c81e35981583c4569b51b8
content_type: application/pdf
creator: dernst
date_created: 2019-05-20T07:33:54Z
date_updated: 2020-07-14T12:47:31Z
file_id: '6471'
file_name: 2019_NatureComm_Chassin.pdf
file_size: 1191827
relation: main_file
file_date_updated: 2020-07-14T12:47:31Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
issue: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1038/s41467-023-36111-0
scopus_import: '1'
status: public
title: A modular degron library for synthetic circuits in mammalian 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: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 10
year: '2019'
...
---
_id: '7147'
abstract:
- lang: eng
text: "The expression of a gene is characterised by its transcription factors and
the function processing them. If the transcription factors are not affected by
gene products, the regulating function is often represented as a combinational
logic circuit, where the outputs (product) are determined by current input values
(transcription factors) only, and are hence independent on their relative arrival
times. However, the simultaneous arrival of transcription factors (TFs) in genetic
circuits is a strong assumption, given that the processes of transcription and
translation of a gene into a protein introduce intrinsic time delays and that
there is no global synchronisation among the arrival times of different molecular
species at molecular targets.\r\n\r\nIn this paper, we construct an experimentally
implementable genetic circuit with two inputs and a single output, such that,
in presence of small delays in input arrival, the circuit exhibits qualitatively
distinct observable phenotypes. In particular, these phenotypes are long lived
transients: they all converge to a single value, but so slowly, that they seem
stable for an extended time period, longer than typical experiment duration. We
used rule-based language to prototype our circuit, and we implemented a search
for finding the parameter combinations raising the phenotypes of interest.\r\n\r\nThe
behaviour of our prototype circuit has wide implications. First, it suggests that
GRNs can exploit event timing to create phenotypes. Second, it opens the possibility
that GRNs are using event timing to react to stimuli and memorise events, without
explicit feedback in regulation. From the modelling perspective, our prototype
circuit demonstrates the critical importance of analysing the transient dynamics
at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions."
alternative_title:
- LNCS
article_processing_charge: No
author:
- 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: Thomas A
full_name: Henzinger, Thomas A
id: 40876CD8-F248-11E8-B48F-1D18A9856A87
last_name: Henzinger
orcid: 0000−0002−2985−7724
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
orcid: 0000-0001-7777-546X
- first_name: Tatjana
full_name: Petrov, Tatjana
id: 3D5811FC-F248-11E8-B48F-1D18A9856A87
last_name: Petrov
orcid: 0000-0002-9041-0905
- first_name: Ali
full_name: Sezgin, Ali
id: 4C7638DA-F248-11E8-B48F-1D18A9856A87
last_name: Sezgin
citation:
ama: 'Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. Transient memory in gene
regulation. In: 17th International Conference on Computational Methods in Systems
Biology. Vol 11773. Springer Nature; 2019:155-187. doi:10.1007/978-3-030-31304-3_9'
apa: 'Guet, C. C., Henzinger, T. A., Igler, C., Petrov, T., & Sezgin, A. (2019).
Transient memory in gene regulation. In 17th International Conference on Computational
Methods in Systems Biology (Vol. 11773, pp. 155–187). Trieste, Italy: Springer
Nature. https://doi.org/10.1007/978-3-030-31304-3_9'
chicago: Guet, Calin C, Thomas A Henzinger, Claudia Igler, Tatjana Petrov, and Ali
Sezgin. “Transient Memory in Gene Regulation.” In 17th International Conference
on Computational Methods in Systems Biology, 11773:155–87. Springer Nature,
2019. https://doi.org/10.1007/978-3-030-31304-3_9.
ieee: C. C. Guet, T. A. Henzinger, C. Igler, T. Petrov, and A. Sezgin, “Transient
memory in gene regulation,” in 17th International Conference on Computational
Methods in Systems Biology, Trieste, Italy, 2019, vol. 11773, pp. 155–187.
ista: 'Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. 2019. Transient memory
in gene regulation. 17th International Conference on Computational Methods in
Systems Biology. CMSB: Computational Methods in Systems Biology, LNCS, vol. 11773,
155–187.'
mla: Guet, Calin C., et al. “Transient Memory in Gene Regulation.” 17th International
Conference on Computational Methods in Systems Biology, vol. 11773, Springer
Nature, 2019, pp. 155–87, doi:10.1007/978-3-030-31304-3_9.
short: C.C. Guet, T.A. Henzinger, C. Igler, T. Petrov, A. Sezgin, in:, 17th International
Conference on Computational Methods in Systems Biology, Springer Nature, 2019,
pp. 155–187.
conference:
end_date: 2019-09-20
location: Trieste, Italy
name: 'CMSB: Computational Methods in Systems Biology'
start_date: 2019-09-18
date_created: 2019-12-04T16:07:50Z
date_published: 2019-09-17T00:00:00Z
date_updated: 2026-04-16T10:26:49Z
day: '17'
department:
- _id: CaGu
- _id: ToHe
doi: 10.1007/978-3-030-31304-3_9
external_id:
isi:
- '000557875100009'
intvolume: ' 11773'
isi: 1
language:
- iso: eng
month: '09'
oa_version: None
page: 155-187
project:
- _id: 25F42A32-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z211
name: Formal methods for the design and analysis of complex systems
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
grant_number: '24573'
name: Design principles underlying genetic switch architecture
publication: 17th International Conference on Computational Methods in Systems Biology
publication_identifier:
eisbn:
- '9783030313043'
eissn:
- 1611-3349
isbn:
- '9783030313036'
issn:
- 0302-9743
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Transient memory in gene regulation
type: conference
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 11773
year: '2019'
...
---
OA_place: publisher
_id: '6371'
abstract:
- lang: eng
text: "Decades of studies have revealed the mechanisms of gene regulation in molecular
detail. We make use of such well-described regulatory systems to explore how the
molecular mechanisms of protein-protein and protein-DNA interactions shape the
dynamics and evolution of gene regulation. \r\n\r\ni) We uncover how the biophysics
of protein-DNA binding determines the potential of regulatory networks to evolve
and adapt, which can be captured using a simple mathematical model. \r\nii) The
evolution of regulatory connections can lead to a significant amount of crosstalk
between binding proteins. We explore the effect of crosstalk on gene expression
from a target promoter, which seems to be modulated through binding competition
at non-specific DNA sites. \r\niii) We investigate how the very same biophysical
characteristics as in i) can generate significant fitness costs for cells through
global crosstalk, meaning non-specific DNA binding across the genomic background.
\r\niv) Binding competition between proteins at a target promoter is a prevailing
regulatory feature due to the prevalence of co-regulation at bacterial promoters.
However, the dynamics of these systems are not always straightforward to determine
even if the molecular mechanisms of regulation are known. A detailed model of
the biophysical interactions reveals that interference between the regulatory
proteins can constitute a new, generic form of system memory that records the
history of the input signals at the promoter. \r\n\r\nWe demonstrate how the biophysics
of protein-DNA binding can be harnessed to investigate the principles that shape
and ultimately limit cellular gene regulation. These results provide a basis for
studies of higher-level functionality, which arises from the underlying regulation.
\ \r\n"
alternative_title:
- ISTA Thesis
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
citation:
ama: Igler C. On the nature of gene regulatory design - The biophysics of transcription
factor binding shapes gene regulation. 2019. doi:10.15479/AT:ISTA:6371
apa: Igler, C. (2019). On the nature of gene regulatory design - The biophysics
of transcription factor binding shapes gene regulation. Institute of Science
and Technology Austria. https://doi.org/10.15479/AT:ISTA:6371
chicago: Igler, Claudia. “On the Nature of Gene Regulatory Design - The Biophysics
of Transcription Factor Binding Shapes Gene Regulation.” Institute of Science
and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6371.
ieee: C. Igler, “On the nature of gene regulatory design - The biophysics of transcription
factor binding shapes gene regulation,” Institute of Science and Technology Austria,
2019.
ista: Igler C. 2019. On the nature of gene regulatory design - The biophysics of
transcription factor binding shapes gene regulation. Institute of Science and
Technology Austria.
mla: Igler, Claudia. On the Nature of Gene Regulatory Design - The Biophysics
of Transcription Factor Binding Shapes Gene Regulation. Institute of Science
and Technology Austria, 2019, doi:10.15479/AT:ISTA:6371.
short: C. Igler, On the Nature of Gene Regulatory Design - The Biophysics of Transcription
Factor Binding Shapes Gene Regulation, Institute of Science and Technology Austria,
2019.
corr_author: '1'
date_created: 2019-05-03T11:55:51Z
date_published: 2019-05-03T00:00:00Z
date_updated: 2026-04-08T13:56:27Z
day: '03'
ddc:
- '576'
- '579'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:6371
file:
- access_level: open_access
checksum: c0085d47c58c9cbcab1b0a783480f6da
content_type: application/pdf
creator: cigler
date_created: 2019-05-03T11:54:52Z
date_updated: 2021-02-11T11:17:13Z
embargo: 2020-05-02
file_id: '6373'
file_name: IglerClaudia_OntheNatureofGeneRegulatoryDesign.pdf
file_size: 12597663
relation: main_file
- access_level: closed
checksum: 2eac954de1c8bbf7e6fb35ed0221ae8c
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: cigler
date_created: 2019-05-03T11:54:54Z
date_updated: 2020-07-14T12:47:28Z
embargo_to: open_access
file_id: '6374'
file_name: IglerClaudia_OntheNatureofGeneRegulatoryDesign.docx
file_size: 34644426
relation: source_file
file_date_updated: 2021-02-11T11:17:13Z
has_accepted_license: '1'
keyword:
- gene regulation
- biophysics
- transcription factor binding
- bacteria
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '152'
project:
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
grant_number: '24573'
name: Design principles underlying genetic switch architecture
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '67'
relation: part_of_dissertation
status: public
- id: '5585'
relation: popular_science
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: On the nature of gene regulatory design - The biophysics of transcription factor
binding shapes gene regulation
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2019'
...
---
_id: '305'
abstract:
- lang: eng
text: The hanging-drop network (HDN) is a technology platform based on a completely
open microfluidic network at the bottom of an inverted, surface-patterned substrate.
The platform is predominantly used for the formation, culturing, and interaction
of self-assembled spherical microtissues (spheroids) under precisely controlled
flow conditions. Here, we describe design, fabrication, and operation of microfluidic
hanging-drop networks.
acknowledgement: This work was financially supported by FP7 of the EU through the
project “Body on a chip,” ICT-FET-296257, and the ERC Advanced Grant “NeuroCMOS”
(contract 267351), as well as by an individual Ambizione Grant 142440 from the Swiss
National Science Foundation for Olivier Frey. The research leading to these results
also 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]. We would like to thank Alexander Stettler, ETH Zurich for his expertise
and support in the cleanroom, and we acknowledge the Single Cell Unit of D-BSSE,
ETH Zurich for assistance in microscopy issues. M.L. is grateful to the members
of the Guet and Tkačik groups, IST Austria, for valuable comments and support.
alternative_title:
- MIMB
author:
- first_name: Patrick
full_name: Misun, Patrick
last_name: Misun
- first_name: Axel
full_name: Birchler, Axel
last_name: Birchler
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Andreas
full_name: Hierlemann, Andreas
last_name: Hierlemann
- first_name: Olivier
full_name: Frey, Olivier
last_name: Frey
citation:
ama: Misun P, Birchler A, Lang M, Hierlemann A, Frey O. Fabrication and operation
of microfluidic hanging drop networks. Methods in Molecular Biology. 2018;1771:183-202.
doi:10.1007/978-1-4939-7792-5_15
apa: Misun, P., Birchler, A., Lang, M., Hierlemann, A., & Frey, O. (2018). Fabrication
and operation of microfluidic hanging drop networks. Methods in Molecular Biology.
Springer. https://doi.org/10.1007/978-1-4939-7792-5_15
chicago: Misun, Patrick, Axel Birchler, Moritz Lang, Andreas Hierlemann, and Olivier
Frey. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods
in Molecular Biology. Springer, 2018. https://doi.org/10.1007/978-1-4939-7792-5_15.
ieee: P. Misun, A. Birchler, M. Lang, A. Hierlemann, and O. Frey, “Fabrication and
operation of microfluidic hanging drop networks,” Methods in Molecular Biology,
vol. 1771. Springer, pp. 183–202, 2018.
ista: Misun P, Birchler A, Lang M, Hierlemann A, Frey O. 2018. Fabrication and operation
of microfluidic hanging drop networks. Methods in Molecular Biology. 1771, 183–202.
mla: Misun, Patrick, et al. “Fabrication and Operation of Microfluidic Hanging Drop
Networks.” Methods in Molecular Biology, vol. 1771, Springer, 2018, pp.
183–202, doi:10.1007/978-1-4939-7792-5_15.
short: P. Misun, A. Birchler, M. Lang, A. Hierlemann, O. Frey, Methods in Molecular
Biology 1771 (2018) 183–202.
date_created: 2018-12-11T11:45:43Z
date_published: 2018-01-01T00:00:00Z
date_updated: 2021-01-12T07:40:42Z
day: '01'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1007/978-1-4939-7792-5_15
ec_funded: 1
intvolume: ' 1771'
language:
- iso: eng
month: '01'
oa_version: None
page: 183 - 202
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Methods in Molecular Biology
publication_status: published
publisher: Springer
publist_id: '7574'
quality_controlled: '1'
scopus_import: 1
status: public
title: Fabrication and operation of microfluidic hanging drop networks
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1771
year: '2018'
...
---
_id: '19'
abstract:
- lang: eng
text: Bacteria regulate genes to survive antibiotic stress, but regulation can be
far from perfect. When regulation is not optimal, mutations that change gene expression
can contribute to antibiotic resistance. It is not systematically understood to
what extent natural gene regulation is or is not optimal for distinct antibiotics,
and how changes in expression of specific genes quantitatively affect antibiotic
resistance. Here we discover a simple quantitative relation between fitness, gene
expression, and antibiotic potency, which rationalizes our observation that a
multitude of genes and even innate antibiotic defense mechanisms have expression
that is critically nonoptimal under antibiotic treatment. First, we developed
a pooled-strain drug-diffusion assay and screened Escherichia coli overexpression
and knockout libraries, finding that resistance to a range of 31 antibiotics could
result from changing expression of a large and functionally diverse set of genes,
in a primarily but not exclusively drug-specific manner. Second, by synthetically
controlling the expression of single-drug and multidrug resistance genes, we observed
that their fitness-expression functions changed dramatically under antibiotic
treatment in accordance with a log-sensitivity relation. Thus, because many genes
are nonoptimally expressed under antibiotic treatment, many regulatory mutations
can contribute to resistance by altering expression and by activating latent defenses.
article_processing_charge: No
article_type: original
author:
- first_name: Adam
full_name: Palmer, Adam
last_name: Palmer
- 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: Roy
full_name: Kishony, Roy
last_name: Kishony
citation:
ama: Palmer A, Chait RP, Kishony R. Nonoptimal gene expression creates latent potential
for antibiotic resistance. Molecular Biology and Evolution. 2018;35(11):2669-2684.
doi:10.1093/molbev/msy163
apa: Palmer, A., Chait, R. P., & Kishony, R. (2018). Nonoptimal gene expression
creates latent potential for antibiotic resistance. Molecular Biology and Evolution.
Oxford University Press. https://doi.org/10.1093/molbev/msy163
chicago: Palmer, Adam, Remy P Chait, and Roy Kishony. “Nonoptimal Gene Expression
Creates Latent Potential for Antibiotic Resistance.” Molecular Biology and
Evolution. Oxford University Press, 2018. https://doi.org/10.1093/molbev/msy163.
ieee: A. Palmer, R. P. Chait, and R. Kishony, “Nonoptimal gene expression creates
latent potential for antibiotic resistance,” Molecular Biology and Evolution,
vol. 35, no. 11. Oxford University Press, pp. 2669–2684, 2018.
ista: Palmer A, Chait RP, Kishony R. 2018. Nonoptimal gene expression creates latent
potential for antibiotic resistance. Molecular Biology and Evolution. 35(11),
2669–2684.
mla: Palmer, Adam, et al. “Nonoptimal Gene Expression Creates Latent Potential for
Antibiotic Resistance.” Molecular Biology and Evolution, vol. 35, no. 11,
Oxford University Press, 2018, pp. 2669–84, doi:10.1093/molbev/msy163.
short: A. Palmer, R.P. Chait, R. Kishony, Molecular Biology and Evolution 35 (2018)
2669–2684.
date_created: 2018-12-11T11:44:11Z
date_published: 2018-08-28T00:00:00Z
date_updated: 2023-10-17T11:51:06Z
day: '28'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1093/molbev/msy163
external_id:
isi:
- '000452567200006'
pmid:
- '30169679'
intvolume: ' 35'
isi: 1
issue: '11'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pubmed/30169679
month: '08'
oa: 1
oa_version: Submitted Version
page: 2669 - 2684
pmid: 1
publication: Molecular Biology and Evolution
publication_identifier:
issn:
- 0737-4038
publication_status: published
publisher: Oxford University Press
publist_id: '8036'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nonoptimal gene expression creates latent potential for antibiotic resistance
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 35
year: '2018'
...
---
_id: '161'
abstract:
- lang: eng
text: 'Which properties of metabolic networks can be derived solely from stoichiometry?
Predictive results have been obtained by flux balance analysis (FBA), by postulating
that cells set metabolic fluxes to maximize growth rate. Here we consider a generalization
of FBA to single-cell level using maximum entropy modeling, which we extend and
test experimentally. Specifically, we define for Escherichia coli metabolism a
flux distribution that yields the experimental growth rate: the model, containing
FBA as a limit, provides a better match to measured fluxes and it makes a wide
range of predictions: on flux variability, regulation, and correlations; on the
relative importance of stoichiometry vs. optimization; on scaling relations for
growth rate distributions. We validate the latter here with single-cell data at
different sub-inhibitory antibiotic concentrations. The model quantifies growth
optimization as emerging from the interplay of competitive dynamics in the population
and regulation of metabolism at the level of single cells.'
article_number: '2988'
article_processing_charge: No
author:
- first_name: Daniele
full_name: De Martino, Daniele
id: 3FF5848A-F248-11E8-B48F-1D18A9856A87
last_name: De Martino
orcid: 0000-0002-5214-4706
- first_name: Andersson Anna
full_name: Mc, Andersson Anna
last_name: Mc
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- 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: Gasper
full_name: Tkacik, Gasper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkacik
orcid: 0000-0002-6699-1455
citation:
ama: De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. Statistical mechanics
for metabolic networks during steady state growth. Nature Communications.
2018;9(1). doi:10.1038/s41467-018-05417-9
apa: De Martino, D., Mc, A. A., Bergmiller, T., Guet, C. C., & Tkačik, G. (2018).
Statistical mechanics for metabolic networks during steady state growth. Nature
Communications. Springer Nature. https://doi.org/10.1038/s41467-018-05417-9
chicago: De Martino, Daniele, Andersson Anna Mc, Tobias Bergmiller, Calin C Guet,
and Gašper Tkačik. “Statistical Mechanics for Metabolic Networks during Steady
State Growth.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-05417-9.
ieee: D. De Martino, A. A. Mc, T. Bergmiller, C. C. Guet, and G. Tkačik, “Statistical
mechanics for metabolic networks during steady state growth,” Nature Communications,
vol. 9, no. 1. Springer Nature, 2018.
ista: De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. 2018. Statistical mechanics
for metabolic networks during steady state growth. Nature Communications. 9(1),
2988.
mla: De Martino, Daniele, et al. “Statistical Mechanics for Metabolic Networks during
Steady State Growth.” Nature Communications, vol. 9, no. 1, 2988, Springer
Nature, 2018, doi:10.1038/s41467-018-05417-9.
short: D. De Martino, A.A. Mc, T. Bergmiller, C.C. Guet, G. Tkačik, Nature Communications
9 (2018).
date_created: 2018-12-11T11:44:57Z
date_published: 2018-07-30T00:00:00Z
date_updated: 2025-04-15T06:50:08Z
day: '30'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.1038/s41467-018-05417-9
ec_funded: 1
external_id:
isi:
- '000440149300021'
file:
- access_level: open_access
checksum: 3ba7ab27b27723c7dcf633e8fc1f8f18
content_type: application/pdf
creator: dernst
date_created: 2018-12-17T16:44:28Z
date_updated: 2020-07-14T12:45:06Z
file_id: '5728'
file_name: 2018_NatureComm_DeMartino.pdf
file_size: 1043205
relation: main_file
file_date_updated: 2020-07-14T12:45:06Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Nature Communications
publication_status: published
publisher: Springer Nature
publist_id: '7760'
quality_controlled: '1'
related_material:
record:
- id: '5587'
relation: popular_science
status: public
scopus_import: '1'
status: public
title: Statistical mechanics for metabolic networks during steady state growth
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: 9
year: '2018'
...
---
_id: '82'
abstract:
- lang: eng
text: In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage,
bacterial cells resistant to the phage commonly emerge and become the dominant
population of bacteria. Following the ascent of resistant mutants, the densities
of bacteria in these simple communities become limited by resources rather than
the phage. Despite the evolution of resistant hosts, upon which the phage cannot
replicate, the lytic phage population is most commonly maintained in an apparently
stable state with the resistant bacteria. Several mechanisms have been put forward
to account for this result. Here we report the results of population dynamic/evolution
experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli
in serial transfer cultures. We show that, following the ascent of λVIR-resistant
bacteria, λVIRis maintained in the majority of cases in maltose-limited minimal
media and in all cases in nutrient-rich broth. Using mathematical models and experiments,
we show that the dominant mechanism responsible for maintenance of λVIRin these
resource-limited populations dominated by resistant E. coli is a high rate of
either phenotypic or genetic transition from resistance to susceptibility—a hitherto
undemonstrated mechanism we term "leaky resistance." We discuss the
implications of leaky resistance to our understanding of the conditions for the
maintenance of phage in populations of bacteria—their “existence conditions.”.
article_number: '2005971'
article_processing_charge: Yes
author:
- first_name: Waqas
full_name: Chaudhry, Waqas
last_name: Chaudhry
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Nilang
full_name: Shah, Nilang
last_name: Shah
- first_name: Howard
full_name: Weiss, Howard
last_name: Weiss
- first_name: Ingrid
full_name: Mccall, Ingrid
last_name: Mccall
- first_name: Justin
full_name: Meyer, Justin
last_name: Meyer
- first_name: Animesh
full_name: Gupta, Animesh
last_name: Gupta
- 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: Bruce
full_name: Levin, Bruce
last_name: Levin
citation:
ama: Chaudhry W, Pleska M, Shah N, et al. Leaky resistance and the conditions for
the existence of lytic bacteriophage. PLoS Biology. 2018;16(8). doi:10.1371/journal.pbio.2005971
apa: Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin,
B. (2018). Leaky resistance and the conditions for the existence of lytic bacteriophage.
PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.2005971
chicago: Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall,
Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Leaky Resistance
and the Conditions for the Existence of Lytic Bacteriophage.” PLoS Biology.
Public Library of Science, 2018. https://doi.org/10.1371/journal.pbio.2005971.
ieee: W. Chaudhry et al., “Leaky resistance and the conditions for the existence
of lytic bacteriophage,” PLoS Biology, vol. 16, no. 8. Public Library of
Science, 2018.
ista: Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC,
Levin B. 2018. Leaky resistance and the conditions for the existence of lytic
bacteriophage. PLoS Biology. 16(8), 2005971.
mla: Chaudhry, Waqas, et al. “Leaky Resistance and the Conditions for the Existence
of Lytic Bacteriophage.” PLoS Biology, vol. 16, no. 8, 2005971, Public
Library of Science, 2018, doi:10.1371/journal.pbio.2005971.
short: W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta,
C.C. Guet, B. Levin, PLoS Biology 16 (2018).
date_created: 2018-12-11T11:44:32Z
date_published: 2018-08-16T00:00:00Z
date_updated: 2023-09-13T08:45:41Z
day: '16'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1371/journal.pbio.2005971
external_id:
isi:
- '000443383300024'
file:
- access_level: open_access
checksum: 527076f78265cd4ea192cd1569851587
content_type: application/pdf
creator: dernst
date_created: 2018-12-17T12:55:31Z
date_updated: 2020-07-14T12:48:10Z
file_id: '5706'
file_name: 2018_Plos_Chaudhry.pdf
file_size: 4007095
relation: main_file
file_date_updated: 2020-07-14T12:48:10Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
issue: '8'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
publication: PLoS Biology
publication_status: published
publisher: Public Library of Science
publist_id: '7972'
quality_controlled: '1'
related_material:
record:
- id: '9810'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Leaky resistance and the conditions for the existence of lytic bacteriophage
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: 16
year: '2018'
...
---
_id: '9810'
article_processing_charge: No
author:
- first_name: Waqas
full_name: Chaudhry, Waqas
last_name: Chaudhry
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Nilang
full_name: Shah, Nilang
last_name: Shah
- first_name: Howard
full_name: Weiss, Howard
last_name: Weiss
- first_name: Ingrid
full_name: Mccall, Ingrid
last_name: Mccall
- first_name: Justin
full_name: Meyer, Justin
last_name: Meyer
- first_name: Animesh
full_name: Gupta, Animesh
last_name: Gupta
- 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: Bruce
full_name: Levin, Bruce
last_name: Levin
citation:
ama: Chaudhry W, Pleska M, Shah N, et al. Numerical data used in figures. 2018.
doi:10.1371/journal.pbio.2005971.s008
apa: Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin,
B. (2018). Numerical data used in figures. Public Library of Science. https://doi.org/10.1371/journal.pbio.2005971.s008
chicago: Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall,
Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Numerical Data Used
in Figures.” Public Library of Science, 2018. https://doi.org/10.1371/journal.pbio.2005971.s008.
ieee: W. Chaudhry et al., “Numerical data used in figures.” Public Library
of Science, 2018.
ista: Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC,
Levin B. 2018. Numerical data used in figures, Public Library of Science, 10.1371/journal.pbio.2005971.s008.
mla: Chaudhry, Waqas, et al. Numerical Data Used in Figures. Public Library
of Science, 2018, doi:10.1371/journal.pbio.2005971.s008.
short: W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta,
C.C. Guet, B. Levin, (2018).
date_created: 2021-08-06T12:43:44Z
date_published: 2018-08-16T00:00:00Z
date_updated: 2023-09-13T08:45:41Z
day: '16'
department:
- _id: CaGu
doi: 10.1371/journal.pbio.2005971.s008
month: '08'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '82'
relation: used_in_publication
status: public
status: public
title: Numerical data used in figures
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2018'
...
---
_id: '503'
abstract:
- lang: eng
text: Buffers are essential for diluting bacterial cultures for flow cytometry analysis
in order to study bacterial physiology and gene expression parameters based on
fluorescence signals. Using a variety of constitutively expressed fluorescent
proteins in Escherichia coli K-12 strain MG1655, we found strong artifactual changes
in fluorescence levels after dilution into the commonly used flow cytometry buffer
phosphate-buffered saline (PBS) and two other buffer solutions, Tris-HCl and M9
salts. These changes appeared very rapidly after dilution, and were linked to
increased membrane permeability and loss in cell viability. We observed buffer-related
effects in several different E. coli strains, K-12, C and W, but not E. coli B,
which can be partially explained by differences in lipopolysaccharide (LPS) and
outer membrane composition. Supplementing the buffers with divalent cations responsible
for outer membrane stability, Mg2+ and Ca2+, preserved fluorescence signals, membrane
integrity and viability of E. coli. Thus, stabilizing the bacterial outer membrane
is essential for precise and unbiased measurements of fluorescence parameters
using flow cytometry.
acknowledged_ssus:
- _id: Bio
acknowledgement: "We thank R Chait and M Lagator for sharing Bacillus subtilis CR_Y1
and pZS*_2R-cIPtet-Venus-Prm, respectively. We are grateful to T Pilizota and all
members of the Guet lab for critically reading the manuscript. We also thank the
Bioimaging facility at IST Austria for assistance using the FACSAria III system.\r\n\r\n"
article_processing_charge: No
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- 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: Tomasek K, Bergmiller T, Guet CC. Lack of cations in flow cytometry buffers
affect fluorescence signals by reducing membrane stability and viability of Escherichia
coli strains. Journal of Biotechnology. 2018;268:40-52. doi:10.1016/j.jbiotec.2018.01.008
apa: Tomasek, K., Bergmiller, T., & Guet, C. C. (2018). Lack of cations in flow
cytometry buffers affect fluorescence signals by reducing membrane stability and
viability of Escherichia coli strains. Journal of Biotechnology. Elsevier.
https://doi.org/10.1016/j.jbiotec.2018.01.008
chicago: Tomasek, Kathrin, Tobias Bergmiller, and Calin C Guet. “Lack of Cations
in Flow Cytometry Buffers Affect Fluorescence Signals by Reducing Membrane Stability
and Viability of Escherichia Coli Strains.” Journal of Biotechnology. Elsevier,
2018. https://doi.org/10.1016/j.jbiotec.2018.01.008.
ieee: K. Tomasek, T. Bergmiller, and C. C. Guet, “Lack of cations in flow cytometry
buffers affect fluorescence signals by reducing membrane stability and viability
of Escherichia coli strains,” Journal of Biotechnology, vol. 268. Elsevier,
pp. 40–52, 2018.
ista: Tomasek K, Bergmiller T, Guet CC. 2018. Lack of cations in flow cytometry
buffers affect fluorescence signals by reducing membrane stability and viability
of Escherichia coli strains. Journal of Biotechnology. 268, 40–52.
mla: Tomasek, Kathrin, et al. “Lack of Cations in Flow Cytometry Buffers Affect
Fluorescence Signals by Reducing Membrane Stability and Viability of Escherichia
Coli Strains.” Journal of Biotechnology, vol. 268, Elsevier, 2018, pp.
40–52, doi:10.1016/j.jbiotec.2018.01.008.
short: K. Tomasek, T. Bergmiller, C.C. Guet, Journal of Biotechnology 268 (2018)
40–52.
corr_author: '1'
date_created: 2018-12-11T11:46:50Z
date_published: 2018-02-20T00:00:00Z
date_updated: 2024-10-09T20:58:29Z
day: '20'
department:
- _id: CaGu
doi: 10.1016/j.jbiotec.2018.01.008
external_id:
isi:
- '000425715100006'
intvolume: ' 268'
isi: 1
language:
- iso: eng
month: '02'
oa_version: None
page: 40 - 52
publication: Journal of Biotechnology
publication_status: published
publisher: Elsevier
publist_id: '7317'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Lack of cations in flow cytometry buffers affect fluorescence signals by reducing
membrane stability and viability of Escherichia coli strains
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 268
year: '2018'
...