---
OA_place: publisher
_id: '20357'
acknowledged_ssus:
- _id: ScienComp
- _id: E-Lib
acknowledgement: "I would also like to acknowledge the Austrian Academy of Sciences
  for funding through the\r\nDOC Fellowship program (fellowship number 26917), the
  Grants Office at ISTA for their\r\nassistance with the application, and the Scientific
  Computing Unit for their support regarding\r\nhigh-performance computation.\r\n"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Natalia
  full_name: Ruzickova, Natalia
  id: D2761128-D73D-11E9-A1BF-BA0DE6697425
  last_name: Ruzickova
citation:
  ama: Ruzickova N. Effect propagation in biological networks. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20357">10.15479/AT-ISTA-20357</a>
  apa: Ruzickova, N. (2025). <i>Effect propagation in biological networks</i>. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/AT-ISTA-20357">https://doi.org/10.15479/AT-ISTA-20357</a>
  chicago: Ruzickova, Natalia. “Effect Propagation in Biological Networks.” Institute
    of Science and Technology Austria, 2025. <a href="https://doi.org/10.15479/AT-ISTA-20357">https://doi.org/10.15479/AT-ISTA-20357</a>.
  ieee: N. Ruzickova, “Effect propagation in biological networks,” Institute of Science
    and Technology Austria, 2025.
  ista: Ruzickova N. 2025. Effect propagation in biological networks. Institute of
    Science and Technology Austria.
  mla: Ruzickova, Natalia. <i>Effect Propagation in Biological Networks</i>. Institute
    of Science and Technology Austria, 2025, doi:<a href="https://doi.org/10.15479/AT-ISTA-20357">10.15479/AT-ISTA-20357</a>.
  short: N. Ruzickova, Effect Propagation in Biological Networks, Institute of Science
    and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-09-15T17:04:48Z
date_published: 2025-09-15T00:00:00Z
date_updated: 2026-08-10T07:47:56Z
day: '15'
ddc:
- '570'
- '530'
degree_awarded: PhD
department:
- _id: GradSch
- _id: GaTk
doi: 10.15479/AT-ISTA-20357
doi_confirm: '1'
file:
- access_level: closed
  checksum: 0582508d439b233497384f83a8307398
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  creator: cchlebak
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  file_size: 30634378
  relation: main_file
file_date_updated: 2026-08-07T10:57:34Z
has_accepted_license: '1'
keyword:
- gene regulation
- networks
- omnigenic model
- pancreas
- collective behaviour
language:
- iso: eng
month: '09'
oa_version: Published Version
page: '156'
project:
- _id: 7bec9174-9f16-11ee-852c-ded9fe5f810e
  name: Collective behaviour of cells in pancreatic Islets of Langerhans
publication_identifier:
  isbn:
  - 978-3-99078-066-4
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
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  - id: '18525'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
title: Effect propagation in biological networks
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...
---
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:<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.
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
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  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'
...