---
_id: '10307'
abstract:
- lang: eng
  text: Bacteria-host interactions represent a continuous trade-off between benefit
    and risk. Thus, the host immune response is faced with a non-trivial problem –
    accommodate beneficial commensals and remove harmful pathogens. This is especially
    difficult as molecular patterns, such as lipopolysaccharide or specific surface
    organelles such as pili, are conserved in both, commensal and pathogenic bacteria.
    Type 1 pili, tightly regulated by phase variation, are considered an important
    virulence factor of pathogenic bacteria as they facilitate invasion into host
    cells. While invasion represents a de facto passive mechanism for pathogens to
    escape the host immune response, we demonstrate a fundamental role of type 1 pili
    as active modulators of the innate and adaptive immune response.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: PreCl
- _id: EM-Fac
alternative_title:
- ISTA Thesis
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
citation:
  ama: Tomasek K. Pathogenic Escherichia coli hijack the host immune response. 2021.
    doi:<a href="https://doi.org/10.15479/at:ista:10307">10.15479/at:ista:10307</a>
  apa: Tomasek, K. (2021). <i>Pathogenic Escherichia coli hijack the host immune response</i>.
    Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:10307">https://doi.org/10.15479/at:ista:10307</a>
  chicago: Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.”
    Institute of Science and Technology Austria, 2021. <a href="https://doi.org/10.15479/at:ista:10307">https://doi.org/10.15479/at:ista:10307</a>.
  ieee: K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,”
    Institute of Science and Technology Austria, 2021.
  ista: Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response.
    Institute of Science and Technology Austria.
  mla: Tomasek, Kathrin. <i>Pathogenic Escherichia Coli Hijack the Host Immune Response</i>.
    Institute of Science and Technology Austria, 2021, doi:<a href="https://doi.org/10.15479/at:ista:10307">10.15479/at:ista:10307</a>.
  short: K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response,
    Institute of Science and Technology Austria, 2021.
date_created: 2021-11-18T15:05:06Z
date_published: 2021-11-18T00:00:00Z
date_updated: 2023-09-07T13:34:38Z
day: '18'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MiSi
- _id: CaGu
- _id: GradSch
doi: 10.15479/at:ista:10307
file:
- access_level: open_access
  checksum: b39c9e0ef18d0484d537a67551effd02
  content_type: application/pdf
  creator: ktomasek
  date_created: 2021-11-18T15:07:31Z
  date_updated: 2022-12-20T23:30:05Z
  embargo: 2022-11-18
  file_id: '10308'
  file_name: ThesisTomasekKathrin.pdf
  file_size: 13266088
  relation: main_file
- access_level: closed
  checksum: c0c440ee9e5ef1102a518a4f9f023e7c
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: ktomasek
  date_created: 2021-11-18T15:07:46Z
  date_updated: 2022-12-20T23:30:05Z
  embargo_to: open_access
  file_id: '10309'
  file_name: ThesisTomasekKathrin.docx
  file_size: 7539509
  relation: source_file
file_date_updated: 2022-12-20T23:30:05Z
has_accepted_license: '1'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: '73'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '10316'
    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: 0000-0002-4561-241X
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
title: Pathogenic Escherichia coli hijack the host immune response
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2021'
...
---
_id: '8155'
abstract:
- lang: eng
  text: "In the thesis we focus on the interplay of the biophysics and evolution of
    gene regulation. We start by addressing how the type of prokaryotic gene regulation
    – activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional
    crosstalk. We propose that regulatory interference caused by excess regulatory
    proteins in the dense cellular medium – global crosstalk – could be a factor in
    determining which type of gene regulatory network is evolutionarily preferred.
    Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium
    enhancer models that optimize so-called regulatory phenotypes. We find a class
    of models that differ from standard thermodynamic equilibrium models by a single
    parameter that notably increases the regulatory performance. Next chapter addresses
    the question of genotype-phenotype-fitness maps of higher dimensional phenotypes.
    We show that our biophysically realistic approach allows us to understand how
    the mechanisms of promoter function constrain genotypephenotype maps, and how
    they affect the evolutionary trajectories of promoters.\r\nIn the last chapter
    we ask whether the intrinsic instability of gene duplication and amplification
    provides a generic alternative to canonical gene regulation. Using mathematical
    modeling, we show that amplifications can tune gene expression in many environments,
    including those where transcription factor-based schemes are\r\nhard to evolve
    or maintain. "
acknowledgement: For the duration of his PhD, Rok was a recipient of a DOC fellowship
  of the Austrian Academy of Sciences.
alternative_title:
- ISTA Thesis
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. Gene regulation across scales – how biophysical constraints shape evolution.
    2020. doi:<a href="https://doi.org/10.15479/AT:ISTA:8155">10.15479/AT:ISTA:8155</a>
  apa: Grah, R. (2020). <i>Gene regulation across scales – how biophysical constraints
    shape evolution</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:8155">https://doi.org/10.15479/AT:ISTA:8155</a>
  chicago: Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints
    Shape Evolution.” Institute of Science and Technology Austria, 2020. <a href="https://doi.org/10.15479/AT:ISTA:8155">https://doi.org/10.15479/AT:ISTA:8155</a>.
  ieee: R. Grah, “Gene regulation across scales – how biophysical constraints shape
    evolution,” Institute of Science and Technology Austria, 2020.
  ista: Grah R. 2020. Gene regulation across scales – how biophysical constraints
    shape evolution. Institute of Science and Technology Austria.
  mla: Grah, Rok. <i>Gene Regulation across Scales – How Biophysical Constraints Shape
    Evolution</i>. Institute of Science and Technology Austria, 2020, doi:<a href="https://doi.org/10.15479/AT:ISTA:8155">10.15479/AT:ISTA:8155</a>.
  short: R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape
    Evolution, Institute of Science and Technology Austria, 2020.
date_created: 2020-07-23T09:51:28Z
date_published: 2020-07-24T00:00:00Z
date_updated: 2023-09-07T13:13:27Z
day: '24'
ddc:
- '530'
- '570'
degree_awarded: PhD
department:
- _id: CaGu
- _id: GaTk
doi: 10.15479/AT:ISTA:8155
file:
- access_level: open_access
  content_type: application/pdf
  creator: rgrah
  date_created: 2020-07-27T12:00:07Z
  date_updated: 2020-07-27T12:00:07Z
  file_id: '8176'
  file_name: Thesis_RokGrah_200727_convertedNew.pdf
  file_size: 16638998
  relation: main_file
  success: 1
- access_level: closed
  content_type: application/zip
  creator: rgrah
  date_created: 2020-07-27T12:02:23Z
  date_updated: 2020-07-30T13:04:55Z
  file_id: '8177'
  file_name: Thesis_new.zip
  file_size: 347459978
  relation: main_file
file_date_updated: 2020-07-30T13:04:55Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '310'
project:
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
  name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '7675'
    relation: part_of_dissertation
    status: public
  - id: '7569'
    relation: part_of_dissertation
    status: public
  - id: '7652'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
title: Gene regulation across scales – how biophysical constraints shape evolution
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_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:<a href="https://doi.org/10.15479/AT:ISTA:8653">10.15479/AT:ISTA:8653</a>
  apa: Tomanek, I. (2020). <i>The evolution of gene expression by copy number and
    point mutations</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:8653">https://doi.org/10.15479/AT:ISTA:8653</a>
  chicago: Tomanek, Isabella. “The Evolution of Gene Expression by Copy Number and
    Point Mutations.” Institute of Science and Technology Austria, 2020. <a href="https://doi.org/10.15479/AT:ISTA:8653">https://doi.org/10.15479/AT:ISTA:8653</a>.
  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. <i>The Evolution of Gene Expression by Copy Number and Point
    Mutations</i>. Institute of Science and Technology Austria, 2020, doi:<a href="https://doi.org/10.15479/AT:ISTA:8653">10.15479/AT:ISTA:8653</a>.
  short: I. Tomanek, The Evolution of Gene Expression by Copy Number and Point Mutations,
    Institute of Science and Technology Austria, 2020.
date_created: 2020-10-13T13:02:33Z
date_published: 2020-10-13T00:00:00Z
date_updated: 2023-09-07T13:22:42Z
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_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
citation:
  ama: Igler C. On the nature of gene regulatory design - The biophysics of transcription
    factor binding shapes gene regulation. 2019. doi:<a href="https://doi.org/10.15479/AT:ISTA:6371">10.15479/AT:ISTA:6371</a>
  apa: Igler, C. (2019). <i>On the nature of gene regulatory design - The biophysics
    of transcription factor binding shapes gene regulation</i>. Institute of Science
    and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:6371">https://doi.org/10.15479/AT:ISTA:6371</a>
  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. <a href="https://doi.org/10.15479/AT:ISTA:6371">https://doi.org/10.15479/AT:ISTA:6371</a>.
  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. <i>On the Nature of Gene Regulatory Design - The Biophysics
    of Transcription Factor Binding Shapes Gene Regulation</i>. Institute of Science
    and Technology Austria, 2019, doi:<a href="https://doi.org/10.15479/AT:ISTA:6371">10.15479/AT:ISTA:6371</a>.
  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.
date_created: 2019-05-03T11:55:51Z
date_published: 2019-05-03T00:00:00Z
date_updated: 2024-02-21T13:45:52Z
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 (DOC Fellowship)
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...
---
_id: '26'
abstract:
- lang: eng
  text: Expression of genes is a fundamental molecular phenotype that is subject to
    evolution by different types of mutations. Both the rate and the effect of mutations
    may depend on the DNA sequence context of a particular gene or a particular promoter
    sequence. In this thesis I investigate the nature of this dependence using simple
    genetic systems in Escherichia coli. With these systems I explore the evolution
    of constitutive gene expression from random starting sequences at different loci
    on the chromosome and at different locations in sequence space. First, I dissect
    chromosomal neighborhood effects that underlie locus-dependent differences in
    the potential of a gene under selection to become more highly expressed. Next,
    I find that the effects of point mutations in promoter sequences are dependent
    on sequence context, and that an existing energy matrix model performs poorly
    in predicting relative expression of unrelated sequences. Finally, I show that
    a substantial fraction of random sequences contain functional promoters and I
    present an extended thermodynamic model that predicts promoter strength in full
    sequence space. Taken together, these results provide new insights and guides
    on how to integrate information on sequence context to improve our qualitative
    and quantitative understanding of bacterial gene expression, with implications
    for rapid evolution of drug resistance, de novo evolution of genes, and horizontal
    gene transfer.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Magdalena
  full_name: Steinrück, Magdalena
  id: 2C023F40-F248-11E8-B48F-1D18A9856A87
  last_name: Steinrück
  orcid: 0000-0003-1229-9719
citation:
  ama: Steinrück M. The influence of sequence context on the evolution of bacterial
    gene expression. 2018. doi:<a href="https://doi.org/10.15479/AT:ISTA:th1059">10.15479/AT:ISTA:th1059</a>
  apa: Steinrück, M. (2018). <i>The influence of sequence context on the evolution
    of bacterial gene expression</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/AT:ISTA:th1059">https://doi.org/10.15479/AT:ISTA:th1059</a>
  chicago: Steinrück, Magdalena. “The Influence of Sequence Context on the Evolution
    of Bacterial Gene Expression.” Institute of Science and Technology Austria, 2018.
    <a href="https://doi.org/10.15479/AT:ISTA:th1059">https://doi.org/10.15479/AT:ISTA:th1059</a>.
  ieee: M. Steinrück, “The influence of sequence context on the evolution of bacterial
    gene expression,” Institute of Science and Technology Austria, 2018.
  ista: Steinrück M. 2018. The influence of sequence context on the evolution of bacterial
    gene expression. Institute of Science and Technology Austria.
  mla: Steinrück, Magdalena. <i>The Influence of Sequence Context on the Evolution
    of Bacterial Gene Expression</i>. Institute of Science and Technology Austria,
    2018, doi:<a href="https://doi.org/10.15479/AT:ISTA:th1059">10.15479/AT:ISTA:th1059</a>.
  short: M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial
    Gene Expression, Institute of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:44:14Z
date_published: 2018-10-30T00:00:00Z
date_updated: 2023-09-07T12:48:43Z
day: '30'
ddc:
- '576'
- '579'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:th1059
file:
- access_level: closed
  checksum: 413cbce1cd1debeae3abe2a25dbc70d1
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: dernst
  date_created: 2019-02-08T10:51:22Z
  date_updated: 2020-07-14T12:45:43Z
  embargo_to: open_access
  file_id: '5941'
  file_name: Thesis_Steinrueck_final.docx
  file_size: 9190845
  relation: source_file
- access_level: open_access
  checksum: 3def8b7854c8b42d643597ce0215efac
  content_type: application/pdf
  creator: dernst
  date_created: 2019-02-08T10:51:22Z
  date_updated: 2021-02-11T11:17:14Z
  embargo: 2019-11-02
  file_id: '5942'
  file_name: Thesis_Steinrueck_final.pdf
  file_size: 7521973
  relation: main_file
file_date_updated: 2021-02-11T11:17:14Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '109'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8029'
pubrep_id: '1059'
related_material:
  record:
  - id: '704'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
title: The influence of sequence context on the evolution of bacterial gene expression
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '202'
abstract:
- lang: eng
  text: 'Restriction-modification (RM) represents the simplest and possibly the most
    widespread mechanism of self/non-self discrimination in nature. In order to provide
    bacteria with immunity against bacteriophages and other parasitic genetic elements,
    RM systems rely on a balance between two enzymes: the restriction enzyme, which
    cleaves non-self DNA at specific restriction sites, and the modification enzyme,
    which tags the host’s DNA as self and thus protects it from cleavage. In this
    thesis, I use population and single-cell level experiments in combination with
    mathematical modeling to study different aspects of the interplay between RM systems,
    bacteria and bacteriophages. First, I analyze how mutations in phage restriction
    sites affect the probability of phage escape – an inherently stochastic process,
    during which phages accidently get modified instead of restricted. Next, I use
    single-cell experiments to show that RM systems can, with a low probability, attack
    the genome of their bacterial host and that this primitive form of autoimmunity
    leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally,
    I investigate the nature of interactions between bacteria, RM systems and temperate
    bacteriophages to find that, as a consequence of phage escape and its impact on
    population dynamics, RM systems can promote acquisition of symbiotic bacteriophages,
    rather than limit it. The results presented here uncover new fundamental biological
    properties of RM systems and highlight their importance in the ecology and evolution
    of bacteria, bacteriophages and their interactions.'
acknowledgement: "During my PhD studies, I received help from many people, all of
  which unfortunately cannot be listed here. I thank them deeply and hope that I never
  made them regret their kindness.\r\nI would like to express my deepest gratitude
  to Călin Guet, who went far beyond his responsibilities as an advisor and was to
  me also a great mentor and a friend. Călin never questioned my potential or lacked
  compassion and I cannot thank him enough for cultivating in me an independent scientist.
  I was amazed by his ability to recognize the most fascinating scientific problems
  in objects of study that others would find mundane. I hope I adopted at least a
  fraction of this ability.\r\nI will be forever grateful to Bruce Levin for all his
  support and especially for giving me the best possible example of how one can practice
  excellent science with humor and style. Working with Bruce was a true privilege.\r\nI
  thank Jonathan Bollback and Gašper Tkačik for serving in my PhD committee and the
  Austrian Academy of Science for funding my PhD research via the DOC fellowship.\r\nI
  thank all our lab members: Tobias Bergmiller for his guidance, especially in the
  first years of my research, and for being a good friend throughout; Remy Chait for
  staying in the lab at unreasonable hours and for the good laughs at bad jokes we
  shared; Anna Staron for supportively listening to my whines whenever I had to run
  a gel; Magdalena Steinrück for her pioneering work in the lab; Kathrin Tomasek for
  keeping the entropic forces in check and for her FACS virtuosity; Isabella Tomanek
  for always being nice to me, no matter how much bench space I took from her.\r\nI
  thank all my collaborators: Reiko Okura and Yuichi Wakamoto for performing and analyzing
  the microfluidic experiments; Long Qian and Edo Kussell for their bioinformatics
  analysis; Dominik Refardt for the λ kan phage; Moritz for his help with the mathematical
  modeling. I thank Fabienne Jesse for her tireless editorial work on all our manuscripts.\r\nFinally,
  I would like to thank my family and especially my wife Edita, who sacrificed a lot
  so that I can pursue my goals and dreams.\r\n"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Maros
  full_name: Pleska, Maros
  id: 4569785E-F248-11E8-B48F-1D18A9856A87
  last_name: Pleska
  orcid: 0000-0001-7460-7479
citation:
  ama: Pleska M. Biology of restriction-modification systems at the single-cell and
    population level. 2017. doi:<a href="https://doi.org/10.15479/AT:ISTA:th_916">10.15479/AT:ISTA:th_916</a>
  apa: Pleska, M. (2017). <i>Biology of restriction-modification systems at the single-cell
    and population level</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:th_916">https://doi.org/10.15479/AT:ISTA:th_916</a>
  chicago: Pleska, Maros. “Biology of Restriction-Modification Systems at the Single-Cell
    and Population Level.” Institute of Science and Technology Austria, 2017. <a href="https://doi.org/10.15479/AT:ISTA:th_916">https://doi.org/10.15479/AT:ISTA:th_916</a>.
  ieee: M. Pleska, “Biology of restriction-modification systems at the single-cell
    and population level,” Institute of Science and Technology Austria, 2017.
  ista: Pleska M. 2017. Biology of restriction-modification systems at the single-cell
    and population level. Institute of Science and Technology Austria.
  mla: Pleska, Maros. <i>Biology of Restriction-Modification Systems at the Single-Cell
    and Population Level</i>. Institute of Science and Technology Austria, 2017, doi:<a
    href="https://doi.org/10.15479/AT:ISTA:th_916">10.15479/AT:ISTA:th_916</a>.
  short: M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell
    and Population Level, Institute of Science and Technology Austria, 2017.
date_created: 2018-12-11T11:45:10Z
date_published: 2017-10-01T00:00:00Z
date_updated: 2023-09-15T12:04:56Z
day: '01'
ddc:
- '576'
- '579'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:th_916
file:
- access_level: open_access
  checksum: 33cfb59674e91f82e3738396d3fb3776
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:08:48Z
  date_updated: 2020-07-14T12:45:24Z
  file_id: '4710'
  file_name: IST-2018-916-v1+3_2017_Pleska_Maros_Thesis.pdf
  file_size: 18569590
  relation: main_file
- access_level: closed
  checksum: dcc239968decb233e7f98cf1083d8c26
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: dernst
  date_created: 2019-04-05T08:33:14Z
  date_updated: 2020-07-14T12:45:24Z
  file_id: '6204'
  file_name: 2017_Pleska_Maros_Thesis.docx
  file_size: 2801649
  relation: source_file
file_date_updated: 2020-07-14T12:45:24Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '126'
project:
- _id: 251D65D8-B435-11E9-9278-68D0E5697425
  grant_number: '24210'
  name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems
    at the Single-Cell Level (DOC Fellowship)
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '7711'
pubrep_id: '916'
related_material:
  record:
  - id: '1243'
    relation: part_of_dissertation
    status: public
  - id: '561'
    relation: part_of_dissertation
    status: public
  - id: '457'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
title: Biology of restriction-modification systems at the single-cell and population
  level
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2017'
...
