---
OA_place: publisher
_id: '14641'
abstract:
- lang: eng
text: "Mutation rates represent the net result of complex interactions among various\r\ncellular
processes and can dramatically influence the evolutionary fate of\r\nmicrobial
populations. However, many popular techniques used to study\r\nmutations are subject
to the confounding effects of heredity and the subtleties\r\nof adaptation to
selection, all of which make it difficult to observe any dynamic\r\nresponses
of mutation rates to fitness challenges. Furthermore, in spite of the\r\nubiquity
of quorum sensing systems across the bacterial domain and relevance\r\nfor many
physiological behaviors, the effects of such mechanisms on mutation\r\nrate and
adaptation remain poorly understood. In the following work, I\r\npresent the development
of a microfluidic droplet-based method to measure\r\nsingle base-pair mutation
rates in growing populations of the bacterium\r\nEscherichia coli. I use this
method to observe a stress-induced increase in\r\nmutation rate that is mediated
by luxS, a highly conserved bacterial quorum\r\nsensing component. I also show
that the aforementioned increase in mutation\r\nrate, and its associated control
by luxS, corresponds to a higher degree of\r\nadaptability under competitive environments."
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: CampIT
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Mike
full_name: Hennessey-Wesen, Mike
id: 3F338C72-F248-11E8-B48F-1D18A9856A87
last_name: Hennessey-Wesen
citation:
ama: Hennessey-Wesen M. Adaptive mutation in E. coli modulated by luxS. 2023. doi:10.15479/at:ista:14641
apa: Hennessey-Wesen, M. (2023). Adaptive mutation in E. coli modulated by luxS.
Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14641
chicago: Hennessey-Wesen, Mike. “Adaptive Mutation in E. Coli Modulated by LuxS.”
Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:14641.
ieee: M. Hennessey-Wesen, “Adaptive mutation in E. coli modulated by luxS,” Institute
of Science and Technology Austria, 2023.
ista: Hennessey-Wesen M. 2023. Adaptive mutation in E. coli modulated by luxS. Institute
of Science and Technology Austria.
mla: Hennessey-Wesen, Mike. Adaptive Mutation in E. Coli Modulated by LuxS.
Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:14641.
short: M. Hennessey-Wesen, Adaptive Mutation in E. Coli Modulated by LuxS, Institute
of Science and Technology Austria, 2023.
corr_author: '1'
date_created: 2023-12-04T13:17:37Z
date_published: 2023-11-30T00:00:00Z
date_updated: 2026-04-07T13:29:59Z
day: '30'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: BjHo
doi: 10.15479/at:ista:14641
ec_funded: 1
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title: Print version
file_date_updated: 2025-07-17T11:20:25Z
has_accepted_license: '1'
keyword:
- microfluidics
- miceobiology
- mutations
- quorum sensing
language:
- iso: eng
month: '11'
oa_version: Published Version
page: '104'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
title: Adaptive mutation in E. coli modulated by luxS
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2023'
...
---
_id: '7383'
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: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
citation:
ama: 'Grah R. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level
Gene Expression regulation. 2020. doi:10.15479/AT:ISTA:7383'
apa: 'Grah, R. (2020). Matlab scripts 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:7383'
chicago: 'Grah, Rok. “Matlab Scripts for the Paper: Gene Amplification as a Form
of Population-Level Gene Expression Regulation.” Institute of Science and Technology
Austria, 2020. https://doi.org/10.15479/AT:ISTA:7383.'
ieee: 'R. Grah, “Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level
Gene Expression regulation.” Institute of Science and Technology Austria, 2020.'
ista: 'Grah R. 2020. Matlab scripts for the Paper: Gene Amplification as a Form
of Population-Level Gene Expression regulation, Institute of Science and Technology
Austria, 10.15479/AT:ISTA:7383.'
mla: 'Grah, Rok. Matlab Scripts for the Paper: Gene Amplification as a Form of
Population-Level Gene Expression Regulation. Institute of Science and Technology
Austria, 2020, doi:10.15479/AT:ISTA:7383.'
short: R. Grah, (2020).
contributor:
- contributor_type: project_leader
first_name: Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
corr_author: '1'
date_created: 2020-01-28T10:41:49Z
date_published: 2020-01-28T00:00:00Z
date_updated: 2025-06-12T07:34:12Z
day: '28'
department:
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- _id: GaTk
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file_size: 962
relation: main_file
file_date_updated: 2020-07-14T12:47:57Z
has_accepted_license: '1'
keyword:
- Matlab scripts
- analysis of microfluidics
- mathematical model
month: '01'
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: 'Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level
Gene Expression regulation'
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
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...
---
_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:
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date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 1 - amplified.
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file_size: 2456192500
relation: main_file
title: Locus1_amplified
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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.
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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
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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'
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title: Locus2_amplified
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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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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
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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
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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
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date_updated: 2020-07-14T12:47:47Z
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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'
...
---
OA_place: publisher
_id: '6891'
abstract:
- lang: eng
text: "While cells of mesenchymal or epithelial origin perform their effector functions
in a purely anchorage dependent manner, cells derived from the hematopoietic lineage
are not committed to operate only within a specific niche. Instead, these cells
are able to function autonomously of the molecular composition in a broad range
of tissue compartments. By this means, cells of the hematopoietic lineage retain
the capacity to disseminate into connective tissue and recirculate between organs,
building the foundation for essential processes such as tissue regeneration or
immune surveillance. \r\nCells of the immune system, specifically leukocytes,
are extraordinarily good at performing this task. These cells are able to flexibly
shift their mode of migration between an adhesion-mediated and an adhesion-independent
manner, instantaneously accommodating for any changes in molecular composition
of the external scaffold. The key component driving directed leukocyte migration
is the chemokine receptor 7, which guides the cell along gradients of chemokine
ligand. Therefore, the physical destination of migrating leukocytes is purely
deterministic, i.e. given by global directional cues such as chemokine gradients.
\r\nNevertheless, these cells typically reside in three-dimensional scaffolds
of inhomogeneous complexity, raising the question whether cells are able to locally
discriminate between multiple optional migration routes. Current literature provides
evidence that leukocytes, specifically dendritic cells, do indeed probe their
surrounding by virtue of multiple explorative protrusions. However, it remains
enigmatic how these cells decide which one is the more favorable route to follow
and what are the key players involved in performing this task. Due to the heterogeneous
environment of most tissues, and the vast adaptability of migrating leukocytes,
at this time it is not clear to what extent leukocytes are able to optimize their
migratory strategy by adapting their level of adhesiveness. And, given the fact
that leukocyte migration is characterized by branched cell shapes in combination
with high migration velocities, it is reasonable to assume that these cells require
fine tuned shape maintenance mechanisms that tightly coordinate protrusion and
adhesion dynamics in a spatiotemporal manner. \r\nTherefore, this study aimed
to elucidate how rapidly migrating leukocytes opt for an ideal migratory path
while maintaining a continuous cell shape and balancing adhesive forces to efficiently
navigate through complex microenvironments. \r\nThe results of this study unraveled
a role for the microtubule cytoskeleton in promoting the decision making process
during path finding and for the first time point towards a microtubule-mediated
function in cell shape maintenance of highly ramified cells such as dendritic
cells. Furthermore, we found that migrating low-adhesive leukocytes are able to
instantaneously adapt to increased tensile load by engaging adhesion receptors.
This response was only occurring tangential to the substrate while adhesive properties
in the vertical direction were not increased. As leukocytes are primed for rapid
migration velocities, these results demonstrate that leukocyte integrins are able
to confer a high level of traction forces parallel to the cell membrane along
the direction of migration without wasting energy in gluing the cell to the substrate.
\r\nThus, the data in the here presented thesis provide new insights into the
pivotal role of cytoskeletal dynamics and the mechanisms of force transduction
during leukocyte migration. \r\nThereby the here presented results help to further
define fundamental principles underlying leukocyte migration and open up potential
therapeutic avenues of clinical relevance.\r\n"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Aglaja
full_name: Kopf, Aglaja
id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
last_name: Kopf
orcid: 0000-0002-2187-6656
citation:
ama: Kopf A. The implication of cytoskeletal dynamics on leukocyte migration. 2019.
doi:10.15479/AT:ISTA:6891
apa: Kopf, A. (2019). The implication of cytoskeletal dynamics on leukocyte migration.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6891
chicago: Kopf, Aglaja. “The Implication of Cytoskeletal Dynamics on Leukocyte Migration.”
Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6891.
ieee: A. Kopf, “The implication of cytoskeletal dynamics on leukocyte migration,”
Institute of Science and Technology Austria, 2019.
ista: Kopf A. 2019. The implication of cytoskeletal dynamics on leukocyte migration.
Institute of Science and Technology Austria.
mla: Kopf, Aglaja. The Implication of Cytoskeletal Dynamics on Leukocyte Migration.
Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6891.
short: A. Kopf, The Implication of Cytoskeletal Dynamics on Leukocyte Migration,
Institute of Science and Technology Austria, 2019.
corr_author: '1'
date_created: 2019-09-19T08:19:44Z
date_published: 2019-07-24T00:00:00Z
date_updated: 2026-04-08T07:11:03Z
day: '24'
ddc:
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degree_awarded: PhD
department:
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doi: 10.15479/AT:ISTA:6891
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date_updated: 2020-10-17T22:30:03Z
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file_size: 52787224
relation: main_file
file_date_updated: 2020-10-17T22:30:03Z
has_accepted_license: '1'
keyword:
- cell biology
- immunology
- leukocyte
- migration
- microfluidics
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '171'
project:
- _id: 265E2996-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W01250-B20
name: Nano-Analytics of Cellular Systems
publication_identifier:
eissn:
- 2663-337X
isbn:
- 978-3-99078-002-2
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
link:
- relation: press_release
url: https://ist.ac.at/en/news/feeling-like-a-cell/
record:
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relation: part_of_dissertation
status: public
- id: '15'
relation: part_of_dissertation
status: public
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relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
title: The implication of cytoskeletal dynamics on leukocyte migration
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2019'
...
---
_id: '5569'
abstract:
- lang: eng
text: "Nela Nikolic, Tobias Bergmiller, Alexandra Vandervelde, Tanino G. Albanese,
Lendert Gelens, and Isabella Moll (2018)\r\n“Autoregulation of mazEF expression
underlies growth heterogeneity in bacterial populations” Nucleic Acids Research,
doi: 10.15479/AT:ISTA:74;\r\nmicroscopy experiments by Tobias Bergmiller; image
and data analysis by Nela Nikolic."
article_processing_charge: No
author:
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- first_name: Nela
full_name: Nikolic, Nela
id: 42D9CABC-F248-11E8-B48F-1D18A9856A87
last_name: Nikolic
orcid: 0000-0001-9068-6090
citation:
ama: Bergmiller T, Nikolic N. Time-lapse microscopy data. 2018. doi:10.15479/AT:ISTA:74
apa: Bergmiller, T., & Nikolic, N. (2018). Time-lapse microscopy data. Institute
of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:74
chicago: Bergmiller, Tobias, and Nela Nikolic. “Time-Lapse Microscopy Data.” Institute
of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:74.
ieee: T. Bergmiller and N. Nikolic, “Time-lapse microscopy data.” Institute of Science
and Technology Austria, 2018.
ista: Bergmiller T, Nikolic N. 2018. Time-lapse microscopy data, Institute of Science
and Technology Austria, 10.15479/AT:ISTA:74.
mla: Bergmiller, Tobias, and Nela Nikolic. Time-Lapse Microscopy Data. Institute
of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:74.
short: T. Bergmiller, N. Nikolic, (2018).
datarep_id: '74'
date_created: 2018-12-12T12:31:35Z
date_published: 2018-02-07T00:00:00Z
date_updated: 2026-04-16T12:20:36Z
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department:
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doi: 10.15479/AT:ISTA:74
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title: Time-lapse microscopy data
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