---
_id: '15270'
abstract:
- lang: eng
text: Various toxic compounds disrupt bacterial physiology. While bacteria harbor
defense mechanisms to mitigate the toxicity, these mechanisms are often coupled
to the physiological state of the cells and become ineffective when the physiology
is severely disrupted.
article_number: '676'
article_processing_charge: Yes
article_type: original
author:
- first_name: Dai
full_name: Le, Dai
last_name: Le
- first_name: Ekaterina
full_name: Krasnopeeva, Ekaterina
id: 1F1EE44A-BF83-11EA-B3C1-BB9CC619BF3A
last_name: Krasnopeeva
- first_name: Faris
full_name: Sinjab, Faris
last_name: Sinjab
- first_name: Teuta
full_name: Pilizota, Teuta
last_name: Pilizota
- first_name: Minsu
full_name: Kim, Minsu
last_name: Kim
citation:
ama: Le D, Krasnopeeva E, Sinjab F, Pilizota T, Kim M. Active efflux leads to heterogeneous
dissipation of proton motive force by protonophores in bacteria. mBio.
2021;12(4). doi:10.1128/mbio.00676-21
apa: Le, D., Krasnopeeva, E., Sinjab, F., Pilizota, T., & Kim, M. (2021). Active
efflux leads to heterogeneous dissipation of proton motive force by protonophores
in bacteria. MBio. American Society for Microbiology. https://doi.org/10.1128/mbio.00676-21
chicago: Le, Dai, Ekaterina Krasnopeeva, Faris Sinjab, Teuta Pilizota, and Minsu
Kim. “Active Efflux Leads to Heterogeneous Dissipation of Proton Motive Force
by Protonophores in Bacteria.” MBio. American Society for Microbiology,
2021. https://doi.org/10.1128/mbio.00676-21.
ieee: D. Le, E. Krasnopeeva, F. Sinjab, T. Pilizota, and M. Kim, “Active efflux
leads to heterogeneous dissipation of proton motive force by protonophores in
bacteria,” mBio, vol. 12, no. 4. American Society for Microbiology, 2021.
ista: Le D, Krasnopeeva E, Sinjab F, Pilizota T, Kim M. 2021. Active efflux leads
to heterogeneous dissipation of proton motive force by protonophores in bacteria.
mBio. 12(4), 676.
mla: Le, Dai, et al. “Active Efflux Leads to Heterogeneous Dissipation of Proton
Motive Force by Protonophores in Bacteria.” MBio, vol. 12, no. 4, 676,
American Society for Microbiology, 2021, doi:10.1128/mbio.00676-21.
short: D. Le, E. Krasnopeeva, F. Sinjab, T. Pilizota, M. Kim, MBio 12 (2021).
date_created: 2024-04-03T07:51:57Z
date_published: 2021-08-31T00:00:00Z
date_updated: 2024-04-10T09:13:59Z
day: '31'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1128/mbio.00676-21
external_id:
pmid:
- '34253054'
file:
- access_level: open_access
checksum: 529e3f97ae5c5f5cc743c4fc130c9440
content_type: application/pdf
creator: dernst
date_created: 2024-04-10T09:05:49Z
date_updated: 2024-04-10T09:05:49Z
file_id: '15309'
file_name: 2021_mBio_Le.pdf
file_size: 1344204
relation: main_file
success: 1
file_date_updated: 2024-04-10T09:05:49Z
has_accepted_license: '1'
intvolume: ' 12'
issue: '4'
keyword:
- Virology
- Microbiology
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: mBio
publication_identifier:
issn:
- 2150-7511
publication_status: published
publisher: American Society for Microbiology
quality_controlled: '1'
status: public
title: Active efflux leads to heterogeneous dissipation of proton motive force by
protonophores in bacteria
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2021'
...
---
_id: '10363'
abstract:
- lang: eng
text: Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death,
but its pro-thrombotic activity is problematic for use of erythropoietin in treating
hypoxia. We constructed a fusion protein that stimulates red blood cell production
and neuroprotection without triggering platelet production, a marker for thrombosis.
The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant
(L108A). The mutation reduces activation of erythropoietin receptor homodimers
that induce erythropoiesis and thrombosis, but maintains the tissue-protective
signaling. The binding of the nanobody element to glycophorin A rescues homodimeric
erythropoietin receptor activation on red blood cell precursors. In a cell proliferation
assay, the fusion protein is active at 10−14 M, allowing an estimate of the number
of receptor–ligand complexes needed for signaling. This fusion protein stimulates
erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity
in vitro. Our erythropoietin fusion protein presents a novel molecule for treating
hypoxia.
acknowledgement: This work was supported by funds from the Wyss Institute for Biologically
Inspired Engineering and the Boston Biomedical Innovation Center (Pilot Award 112475;
Drive Award U54HL119145). J.L., K.M.K., D.R.B., J.C.W. and P.A.S. were supported
by the Harvard Medical School Department of Systems Biology. J.C.W. was further
supported by the Harvard Medical School Laboratory of Systems Pharmacology. A.V.,
D.R.B. and P.A.S. were further supported by the Wyss Institute for Biologically
Inspired Engineering. N.G.G. was sponsored by the Army Research Office under Grant
Number W911NF-17-2-0092. The views and conclusions contained in this document are
those of the authors and should not be interpreted as representing the official
policies, either expressed or implied, of the Army Research Office or the U.S. Government.
The U.S. Government is authorized to reproduce and distribute reprints for Government
purposes notwithstanding any copyright notation herein. We sincerely thank Amanda
Graveline and the Wyss Institute at Harvard for their scientific support.
article_number: gzab025
article_processing_charge: No
article_type: original
author:
- first_name: Jungmin
full_name: Lee, Jungmin
last_name: Lee
- first_name: Andyna
full_name: Vernet, Andyna
last_name: Vernet
- first_name: Nathalie
full_name: Gruber, Nathalie
id: 2C9C8316-AA17-11E9-B5C2-8BC2E5697425
last_name: Gruber
- first_name: Kasia M.
full_name: Kready, Kasia M.
last_name: Kready
- first_name: Devin R.
full_name: Burrill, Devin R.
last_name: Burrill
- first_name: Jeffrey C.
full_name: Way, Jeffrey C.
last_name: Way
- first_name: Pamela A.
full_name: Silver, Pamela A.
last_name: Silver
citation:
ama: Lee J, Vernet A, Gruber N, et al. Rational engineering of an erythropoietin
fusion protein to treat hypoxia. Protein Engineering, Design and Selection.
2021;34. doi:10.1093/protein/gzab025
apa: Lee, J., Vernet, A., Gruber, N., Kready, K. M., Burrill, D. R., Way, J. C.,
& Silver, P. A. (2021). Rational engineering of an erythropoietin fusion protein
to treat hypoxia. Protein Engineering, Design and Selection. Oxford University
Press. https://doi.org/10.1093/protein/gzab025
chicago: Lee, Jungmin, Andyna Vernet, Nathalie Gruber, Kasia M. Kready, Devin R.
Burrill, Jeffrey C. Way, and Pamela A. Silver. “Rational Engineering of an Erythropoietin
Fusion Protein to Treat Hypoxia.” Protein Engineering, Design and Selection.
Oxford University Press, 2021. https://doi.org/10.1093/protein/gzab025.
ieee: J. Lee et al., “Rational engineering of an erythropoietin fusion protein
to treat hypoxia,” Protein Engineering, Design and Selection, vol. 34.
Oxford University Press, 2021.
ista: Lee J, Vernet A, Gruber N, Kready KM, Burrill DR, Way JC, Silver PA. 2021.
Rational engineering of an erythropoietin fusion protein to treat hypoxia. Protein
Engineering, Design and Selection. 34, gzab025.
mla: Lee, Jungmin, et al. “Rational Engineering of an Erythropoietin Fusion Protein
to Treat Hypoxia.” Protein Engineering, Design and Selection, vol. 34,
gzab025, Oxford University Press, 2021, doi:10.1093/protein/gzab025.
short: J. Lee, A. Vernet, N. Gruber, K.M. Kready, D.R. Burrill, J.C. Way, P.A. Silver,
Protein Engineering, Design and Selection 34 (2021).
date_created: 2021-11-28T23:01:28Z
date_published: 2021-11-01T00:00:00Z
date_updated: 2026-06-18T08:37:03Z
day: '01'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1093/protein/gzab025
external_id:
isi:
- '000746596900001'
pmid:
- '34725710'
intvolume: ' 34'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1093/protein/gzab025
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
publication: Protein Engineering, Design and Selection
publication_identifier:
eissn:
- 1741-0134
issn:
- 1741-0126
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Rational engineering of an erythropoietin fusion protein to treat hypoxia
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 34
year: '2021'
...
---
_id: '9046'
acknowledgement: Our work was supported by the Swedish Research Council (grant 2017-01527)
to DIA
article_number: e1009172
article_processing_charge: No
article_type: original
author:
- first_name: Roderich
full_name: Römhild, Roderich
id: 68E56E44-62B0-11EA-B963-444F3DDC885E
last_name: Römhild
orcid: 0000-0001-9480-5261
- first_name: Dan I.
full_name: Andersson, Dan I.
last_name: Andersson
citation:
ama: Römhild R, Andersson DI. Mechanisms and therapeutic potential of collateral
sensitivity to antibiotics. PLoS Pathogens. 2021;17(1). doi:10.1371/journal.ppat.1009172
apa: Römhild, R., & Andersson, D. I. (2021). Mechanisms and therapeutic potential
of collateral sensitivity to antibiotics. PLoS Pathogens. Public Library
of Science. https://doi.org/10.1371/journal.ppat.1009172
chicago: Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential
of Collateral Sensitivity to Antibiotics.” PLoS Pathogens. Public Library
of Science, 2021. https://doi.org/10.1371/journal.ppat.1009172.
ieee: R. Römhild and D. I. Andersson, “Mechanisms and therapeutic potential of collateral
sensitivity to antibiotics,” PLoS Pathogens, vol. 17, no. 1. Public Library
of Science, 2021.
ista: Römhild R, Andersson DI. 2021. Mechanisms and therapeutic potential of collateral
sensitivity to antibiotics. PLoS Pathogens. 17(1), e1009172.
mla: Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential
of Collateral Sensitivity to Antibiotics.” PLoS Pathogens, vol. 17, no.
1, e1009172, Public Library of Science, 2021, doi:10.1371/journal.ppat.1009172.
short: R. Römhild, D.I. Andersson, PLoS Pathogens 17 (2021).
date_created: 2021-01-31T23:01:21Z
date_published: 2021-01-14T00:00:00Z
date_updated: 2025-07-10T12:01:33Z
day: '14'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1371/journal.ppat.1009172
external_id:
isi:
- '000610190400007'
pmid:
- '33444399'
file:
- access_level: open_access
checksum: d745d7f8fcbb9b95fea16a36f94dee31
content_type: application/pdf
creator: dernst
date_created: 2021-02-03T12:13:03Z
date_updated: 2021-02-03T12:13:03Z
file_id: '9070'
file_name: 2021_PlosPathogens_Roemhild.pdf
file_size: 570066
relation: main_file
success: 1
file_date_updated: 2021-02-03T12:13:03Z
has_accepted_license: '1'
intvolume: ' 17'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
publication: PLoS Pathogens
publication_identifier:
eissn:
- 1553-7374
issn:
- 1553-7366
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mechanisms and therapeutic potential of collateral sensitivity to antibiotics
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2021'
...
---
_id: '9283'
abstract:
- lang: eng
text: Gene expression levels are influenced by multiple coexisting molecular mechanisms.
Some of these interactions such as those of transcription factors and promoters
have been studied extensively. However, predicting phenotypes of gene regulatory
networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic
GRN to study in Escherichia coli how network phenotypes depend on local genetic
context, i.e. the genetic neighborhood of a transcription factor and its relative
position. We show that one GRN with fixed topology can display not only quantitatively
but also qualitatively different phenotypes, depending solely on the local genetic
context of its components. Transcriptional read-through is the main molecular
mechanism that places one transcriptional unit (TU) within two separate regulons
without the need for complex regulatory sequences. We propose that relative order
of individual TUs, with its potential for combinatorial complexity, plays an important
role in shaping phenotypes of GRNs.
acknowledgement: "We thank J Bollback, L Hurst, M Lagator, C Nizak, O Rivoire, M Savageau,
G Tkacik, and B Vicozo\r\nfor helpful discussions; A Dolinar and A Greshnova for
technical assistance; T Bollenbach for supplying the strain JW0336; C Rusnac, and
members of the Guet lab for comments. The research leading to these results has
received funding from the People Programme (Marie Curie Actions) of the European
Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n˚\r\n628377
(ANS) and an Austrian Science Fund (FWF) grant n˚ I 3901-B32 (CCG)."
article_number: e65993
article_processing_charge: Yes
article_type: original
author:
- first_name: Anna A
full_name: Nagy-Staron, Anna A
id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
last_name: Nagy-Staron
orcid: 0000-0002-1391-8377
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
- first_name: Caroline
full_name: Caruso Carter, Caroline
last_name: Caruso Carter
- first_name: Elisabeth
full_name: Sonnleitner, Elisabeth
last_name: Sonnleitner
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: Tiago
full_name: Paixão, Tiago
last_name: Paixão
- 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: Nagy-Staron AA, Tomasek K, Caruso Carter C, et al. Local genetic context shapes
the function of a gene regulatory network. eLife. 2021;10. doi:10.7554/elife.65993
apa: Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic,
B., Paixão, T., & Guet, C. C. (2021). Local genetic context shapes the function
of a gene regulatory network. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.65993
chicago: Nagy-Staron, Anna A, Kathrin Tomasek, Caroline Caruso Carter, Elisabeth
Sonnleitner, Bor Kavcic, Tiago Paixão, and Calin C Guet. “Local Genetic Context
Shapes the Function of a Gene Regulatory Network.” ELife. eLife Sciences
Publications, 2021. https://doi.org/10.7554/elife.65993.
ieee: A. A. Nagy-Staron et al., “Local genetic context shapes the function
of a gene regulatory network,” eLife, vol. 10. eLife Sciences Publications,
2021.
ista: Nagy-Staron AA, Tomasek K, Caruso Carter C, Sonnleitner E, Kavcic B, Paixão
T, Guet CC. 2021. Local genetic context shapes the function of a gene regulatory
network. eLife. 10, e65993.
mla: Nagy-Staron, Anna A., et al. “Local Genetic Context Shapes the Function of
a Gene Regulatory Network.” ELife, vol. 10, e65993, eLife Sciences Publications,
2021, doi:10.7554/elife.65993.
short: A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic,
T. Paixão, C.C. Guet, ELife 10 (2021).
corr_author: '1'
date_created: 2021-03-23T10:11:46Z
date_published: 2021-03-08T00:00:00Z
date_updated: 2025-06-12T06:36:17Z
day: '08'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.7554/elife.65993
ec_funded: 1
external_id:
isi:
- '000631050900001'
pmid:
- '33683203'
file:
- access_level: open_access
checksum: 3c2f44058c2dd45a5a1027f09d263f8e
content_type: application/pdf
creator: bkavcic
date_created: 2021-03-23T10:12:58Z
date_updated: 2021-03-23T10:12:58Z
file_id: '9284'
file_name: elife-65993-v2.pdf
file_size: 1390469
relation: main_file
success: 1
file_date_updated: 2021-03-23T10:12:58Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
keyword:
- Genetics and Molecular Biology
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2517526A-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '628377'
name: 'The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic
Networks to Genomic Studies'
- _id: 268BFA92-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03901
name: Cybergenetic circuits to test composability of gene networks
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
record:
- id: '8951'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Local genetic context shapes the function of a gene regulatory network
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 10
year: '2021'
...
---
_id: '9647'
abstract:
- lang: eng
text: 'Gene expression is regulated by the set of transcription factors (TFs) that
bind to the promoter. The ensuing regulating function is often represented as
a combinational logic circuit, where output (gene expression) is determined by
current input values (promoter bound TFs) only. However, the simultaneous arrival
of TFs is a strong assumption, since transcription and translation of genes introduce
intrinsic time delays and there is no global synchronisation among the arrival
times of different molecular species at their targets. We present an experimentally
implementable genetic circuit with two inputs and one output, which in the presence
of small delays in input arrival, exhibits qualitatively distinct population-level
phenotypes, over timescales that are longer than typical cell doubling times.
From a dynamical systems point of view, these phenotypes represent long-lived
transients: although they converge to the same value eventually, they do so after
a very long time span. The key feature of this toy model genetic circuit is that,
despite having only two inputs and one output, it is regulated by twenty-three
distinct DNA-TF configurations, two of which are more stable than others (DNA
looped states), one promoting and another blocking the expression of the output
gene. Small delays in input arrival time result in a majority of cells in the
population quickly reaching the stable state associated with the first input,
while exiting of this stable state occurs at a slow timescale. In order to mechanistically
model the behaviour of this genetic circuit, we used a rule-based modelling language,
and implemented a grid-search to find parameter combinations giving rise to long-lived
transients. Our analysis shows that in the absence of feedback, there exist path-dependent
gene regulatory mechanisms based on the long timescale of transients. The behaviour
of this toy model circuit suggests that gene regulatory networks can exploit event
timing to create phenotypes, and it opens the possibility that they could use
event timing to memorise events, without regulatory feedback. The model reveals
the importance of (i) mechanistically modelling the transitions between the different
DNA-TF states, and (ii) employing transient analysis thereof.'
acknowledgement: 'Tatjana Petrov’s research was supported in part by SNSF Advanced
Postdoctoral Mobility Fellowship grant number P300P2 161067, the Ministry of Science,
Research and the Arts of the state of Baden-Wurttemberg, and the DFG Centre of Excellence
2117 ‘Centre for the Advanced Study of Collective Behaviour’ (ID: 422037984). Claudia
Igler is the recipient of a DOC Fellowship of the Austrian Academy of Sciences.
Thomas A. Henzinger’s research was supported in part by the Austrian Science Fund
(FWF) under grant Z211-N23 (Wittgenstein Award).'
article_processing_charge: No
article_type: original
author:
- first_name: Tatjana
full_name: Petrov, Tatjana
last_name: Petrov
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
- first_name: Ali
full_name: Sezgin, Ali
id: 4C7638DA-F248-11E8-B48F-1D18A9856A87
last_name: Sezgin
- 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: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. Long lived transients in
gene regulation. Theoretical Computer Science. 2021;893:1-16. doi:10.1016/j.tcs.2021.05.023
apa: Petrov, T., Igler, C., Sezgin, A., Henzinger, T. A., & Guet, C. C. (2021).
Long lived transients in gene regulation. Theoretical Computer Science.
Elsevier. https://doi.org/10.1016/j.tcs.2021.05.023
chicago: Petrov, Tatjana, Claudia Igler, Ali Sezgin, Thomas A Henzinger, and Calin
C Guet. “Long Lived Transients in Gene Regulation.” Theoretical Computer Science.
Elsevier, 2021. https://doi.org/10.1016/j.tcs.2021.05.023.
ieee: T. Petrov, C. Igler, A. Sezgin, T. A. Henzinger, and C. C. Guet, “Long lived
transients in gene regulation,” Theoretical Computer Science, vol. 893.
Elsevier, pp. 1–16, 2021.
ista: Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. 2021. Long lived transients
in gene regulation. Theoretical Computer Science. 893, 1–16.
mla: Petrov, Tatjana, et al. “Long Lived Transients in Gene Regulation.” Theoretical
Computer Science, vol. 893, Elsevier, 2021, pp. 1–16, doi:10.1016/j.tcs.2021.05.023.
short: T. Petrov, C. Igler, A. Sezgin, T.A. Henzinger, C.C. Guet, Theoretical Computer
Science 893 (2021) 1–16.
corr_author: '1'
date_created: 2021-07-11T22:01:18Z
date_published: 2021-06-04T00:00:00Z
date_updated: 2025-04-15T06:25:56Z
day: '04'
ddc:
- '004'
department:
- _id: ToHe
- _id: CaGu
doi: 10.1016/j.tcs.2021.05.023
external_id:
isi:
- '000710180500002'
file:
- access_level: open_access
checksum: d3aef34cfb13e53bba4cf44d01680793
content_type: application/pdf
creator: dernst
date_created: 2022-05-12T12:13:27Z
date_updated: 2022-05-12T12:13:27Z
file_id: '11364'
file_name: 2021_TheoreticalComputerScience_Petrov.pdf
file_size: 2566504
relation: main_file
success: 1
file_date_updated: 2022-05-12T12:13:27Z
has_accepted_license: '1'
intvolume: ' 893'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 1-16
project:
- _id: 25F42A32-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z211
name: Formal methods for the design and analysis of complex systems
publication: Theoretical Computer Science
publication_identifier:
issn:
- 0304-3975
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Long lived transients in gene regulation
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 893
year: '2021'
...
---
_id: '9746'
abstract:
- lang: eng
text: Evolutionary adaptation is a major source of antibiotic resistance in bacterial
pathogens. Evolution-informed therapy aims to constrain resistance by accounting
for bacterial evolvability. Sequential treatments with antibiotics that target
different bacterial processes were previously shown to limit adaptation through
genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous
sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly
lead to cross-resistance. We here challenged this assumption by determining the
evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments
involving both heterogenous and homogeneous antibiotic sets. To our surprise,
we found that fast switching between only β-lactam antibiotics resulted in increased
extinction of bacterial populations. We demonstrate that extinction is favored
by low rates of spontaneous resistance emergence and low levels of spontaneous
cross-resistance among the antibiotics in sequence. The uncovered principles may
help to guide the optimized use of available antibiotics in highly potent, evolution-informed
treatment designs.
acknowledgement: We would like to thank Leif Tueffers and João Botelho for discussions
and suggestions as well as Kira Haas and Julia Bunk for technical support. We acknowledge
financial support from the German Science Foundation (grant SCHU 1415/12-2 to HS,
and funding under Germany’s Excellence Strategy EXC 2167–390884018 as well as the
Research Training Group 2501 TransEvo to HS and SN), the Max Planck Society (IMPRS
scholarship to AB; Max-Planck fellowship to HS), and the Leibniz Science Campus
Evolutionary Medicine of the Lung (EvoLUNG, to HS and SN). This work was further
supported by the German Science Foundation Research Infrastructure NGS_CC (project
407495230) as part of the Next Generation Sequencing Competence Network (project
423957469). NGS analyses were carried out at the Competence Centre for Genomic Analysis
Kiel (CCGA Kiel).
article_number: e68876
article_processing_charge: No
article_type: original
author:
- first_name: Aditi
full_name: Batra, Aditi
last_name: Batra
- first_name: Roderich
full_name: Römhild, Roderich
id: 68E56E44-62B0-11EA-B963-444F3DDC885E
last_name: Römhild
orcid: 0000-0001-9480-5261
- first_name: Emilie
full_name: Rousseau, Emilie
last_name: Rousseau
- first_name: Sören
full_name: Franzenburg, Sören
last_name: Franzenburg
- first_name: Stefan
full_name: Niemann, Stefan
last_name: Niemann
- first_name: Hinrich
full_name: Schulenburg, Hinrich
last_name: Schulenburg
citation:
ama: Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. High
potency of sequential therapy with only beta-lactam antibiotics. eLife.
2021;10. doi:10.7554/elife.68876
apa: Batra, A., Römhild, R., Rousseau, E., Franzenburg, S., Niemann, S., & Schulenburg,
H. (2021). High potency of sequential therapy with only beta-lactam antibiotics.
ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.68876
chicago: Batra, Aditi, Roderich Römhild, Emilie Rousseau, Sören Franzenburg, Stefan
Niemann, and Hinrich Schulenburg. “High Potency of Sequential Therapy with Only
Beta-Lactam Antibiotics.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.68876.
ieee: A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, and H. Schulenburg,
“High potency of sequential therapy with only beta-lactam antibiotics,” eLife,
vol. 10. eLife Sciences Publications, 2021.
ista: Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. 2021.
High potency of sequential therapy with only beta-lactam antibiotics. eLife. 10,
e68876.
mla: Batra, Aditi, et al. “High Potency of Sequential Therapy with Only Beta-Lactam
Antibiotics.” ELife, vol. 10, e68876, eLife Sciences Publications, 2021,
doi:10.7554/elife.68876.
short: A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, H. Schulenburg,
ELife 10 (2021).
date_created: 2021-07-28T13:36:57Z
date_published: 2021-07-28T00:00:00Z
date_updated: 2026-06-18T19:56:55Z
day: '28'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.7554/elife.68876
external_id:
isi:
- '000692027800001'
pmid:
- '34318749'
intvolume: ' 10'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.7554/eLife.68876
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: High potency of sequential therapy with only beta-lactam antibiotics
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 10
year: '2021'
...
---
_id: '9822'
abstract:
- lang: eng
text: Attachment of adhesive molecules on cell culture surfaces to restrict cell
adhesion to defined areas and shapes has been vital for the progress of in vitro
research. In currently existing patterning methods, a combination of pattern properties
such as stability, precision, specificity, high-throughput outcome, and spatiotemporal
control is highly desirable but challenging to achieve. Here, we introduce a versatile
and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent
patterning step and a subsequent functionalization of the pattern via click chemistry.
This two-step process is feasible on arbitrary surfaces and allows for generation
of sustainable patterns and gradients. The method is validated in different biological
systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining
the growth and migration of cells to the designated areas. We then implement a
sequential photopatterning approach by adding a second switchable patterning step,
allowing for spatiotemporal control over two distinct surface patterns. As a proof
of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis.
Our results show that the spatiotemporal control provided by our “sequential photopatterning”
system is essential for mimicking dynamic biological processes and that our innovative
approach has great potential for further applications in cell science.
acknowledgement: We would like to thank Charlott Leu for the production of our chromium
wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh
Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim
Rädler for his valuable scientific guidance.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Themistoklis
full_name: Zisis, Themistoklis
last_name: Zisis
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Miriam
full_name: Balles, Miriam
last_name: Balles
- first_name: Maibritt
full_name: Kretschmer, Maibritt
last_name: Kretschmer
- first_name: Maria
full_name: Nemethova, Maria
id: 34E27F1C-F248-11E8-B48F-1D18A9856A87
last_name: Nemethova
- 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: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Janina
full_name: Lange, Janina
last_name: Lange
- 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: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
- first_name: Stefan
full_name: Zahler, Stefan
last_name: Zahler
citation:
ama: Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for
studying cellular processes under spatiotemporal control. ACS Applied Materials
and Interfaces. 2021;13(30):35545–35560. doi:10.1021/acsami.1c09850
apa: Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R.
P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular
processes under spatiotemporal control. ACS Applied Materials and Interfaces.
American Chemical Society. https://doi.org/10.1021/acsami.1c09850
chicago: Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria
Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning
for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied
Materials and Interfaces. American Chemical Society, 2021. https://doi.org/10.1021/acsami.1c09850.
ieee: T. Zisis et al., “Sequential and switchable patterning for studying
cellular processes under spatiotemporal control,” ACS Applied Materials and
Interfaces, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021.
ista: Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild
R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning
for studying cellular processes under spatiotemporal control. ACS Applied Materials
and Interfaces. 13(30), 35545–35560.
mla: Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying
Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and
Interfaces, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560,
doi:10.1021/acsami.1c09850.
short: T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait,
R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials
and Interfaces 13 (2021) 35545–35560.
corr_author: '1'
date_created: 2021-08-08T22:01:28Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2025-07-10T12:02:02Z
day: '04'
ddc:
- '620'
- '570'
department:
- _id: MiSi
- _id: GaTk
- _id: Bio
- _id: CaGu
doi: 10.1021/acsami.1c09850
ec_funded: 1
external_id:
isi:
- '000683741400026'
pmid:
- '34283577'
file:
- access_level: open_access
checksum: b043a91d9f9200e467b970b692687ed3
content_type: application/pdf
creator: asandaue
date_created: 2021-08-09T09:44:03Z
date_updated: 2021-08-09T09:44:03Z
file_id: '9833'
file_name: 2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf
file_size: 7123293
relation: main_file
success: 1
file_date_updated: 2021-08-09T09:44:03Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
issue: '30'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 35545–35560
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
publication: ACS Applied Materials and Interfaces
publication_identifier:
eissn:
- 1944-8252
issn:
- 1944-8244
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Sequential and switchable patterning for studying cellular processes under
spatiotemporal control
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 13
year: '2021'
...
---
OA_place: publisher
_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:10.15479/at:ista:10307
apa: Tomasek, K. (2021). Pathogenic Escherichia coli hijack the host immune response.
Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:10307
chicago: Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.”
Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:10307.
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. Pathogenic Escherichia Coli Hijack the Host Immune Response.
Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:10307.
short: K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response,
Institute of Science and Technology Austria, 2021.
corr_author: '1'
date_created: 2021-11-18T15:05:06Z
date_published: 2021-11-18T00:00:00Z
date_updated: 2026-04-08T07:14:01Z
day: '18'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MiSi
- _id: CaGu
- _id: GradSch
doi: 10.15479/at:ista:10307
file:
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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
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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: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2021'
...
---
_id: '10316'
abstract:
- lang: eng
text: A key attribute of persistent or recurring bacterial infections is the ability
of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express
type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and
establish persistent infections. However, the molecular mechanisms and strategies
by which bacteria actively circumvent the immune response of the host remain poorly
understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide
detection, on dendritic cells as a previously undescribed binding partner of FimH,
the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH
amino acids involved in CD14 binding are highly conserved across pathogenic and
non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced
dendritic cell migration and blunted expression of co-stimulatory molecules, both
rate-limiting factors of T cell activation. While defining an active molecular
mechanism of immune evasion by pathogens, the interaction between FimH and CD14
represents a potential target to interfere with persistent and recurrent infections,
such as urinary tract infections or Crohn’s disease.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra
and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments
and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis.
We thank the IST Austria Scientific Service Units, especially the Bioimaging facility,
the Preclinical facility and the Electron microscopy facility for technical support,
Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions
and Daria Siekhaus for critically reading the manuscript. This work was supported
by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G.,
the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911)
to M.S.
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: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Ivana
full_name: Glatzová, Ivana
id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d
last_name: Glatzová
- first_name: Michael S.
full_name: Lukesch, Michael S.
last_name: Lukesch
- 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: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
citation:
ama: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
bioRxiv. doi:10.1101/2021.10.18.464770
apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &
Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the
host immune response by binding to CD14. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2021.10.18.464770
chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch,
Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli
Hijack the Host Immune Response by Binding to CD14.” BioRxiv. Cold Spring
Harbor Laboratory, n.d. https://doi.org/10.1101/2021.10.18.464770.
ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M.
K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune
response by binding to CD14,” bioRxiv. Cold Spring Harbor Laboratory.
ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
bioRxiv, 10.1101/2021.10.18.464770.
mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack
the Host Immune Response by Binding to CD14.” BioRxiv, Cold Spring Harbor
Laboratory, doi:10.1101/2021.10.18.464770.
short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt,
BioRxiv (n.d.).
corr_author: '1'
date_created: 2021-11-19T12:24:16Z
date_published: 2021-10-18T00:00:00Z
date_updated: 2026-06-24T22:30:50Z
day: '18'
department:
- _id: CaGu
- _id: MiSi
doi: 10.1101/2021.10.18.464770
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1
month: '10'
oa: 1
oa_version: Preprint
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
publication: bioRxiv
publication_status: draft
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '11843'
relation: later_version
status: public
- id: '10307'
relation: dissertation_contains
status: public
status: public
title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response
by binding to CD14
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2021'
...
---
_id: '7569'
abstract:
- lang: eng
text: 'Genes differ in the frequency at which they are expressed and in the form
of regulation used to control their activity. In particular, positive or negative
regulation can lead to activation of a gene in response to an external signal.
Previous works proposed that the form of regulation of a gene correlates with
its frequency of usage: positive regulation when the gene is frequently expressed
and negative regulation when infrequently expressed. Such network design means
that, in the absence of their regulators, the genes are found in their least required
activity state, hence regulatory intervention is often necessary. Due to the multitude
of genes and regulators, spurious binding and unbinding events, called “crosstalk”,
could occur. To determine how the form of regulation affects the global crosstalk
in the network, we used a mathematical model that includes multiple regulators
and multiple target genes. We found that crosstalk depends non-monotonically on
the availability of regulators. Our analysis showed that excess use of regulation
entailed by the formerly suggested network design caused high crosstalk levels
in a large part of the parameter space. We therefore considered the opposite ‘idle’
design, where the default unregulated state of genes is their frequently required
activity state. We found, that ‘idle’ design minimized the use of regulation and
thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae
using transcription factors binding data. We demonstrated that even partial network
data could suffice to estimate its global crosstalk, suggesting its applicability
to additional organisms. We found that S. cerevisiae estimated crosstalk is lower
than that of a random network, suggesting that natural selection reduces crosstalk.
In summary, our study highlights a new type of protein production cost which is
typically overlooked: that of regulatory interference caused by the presence of
excess regulators in the cell. It demonstrates the importance of whole-network
descriptions, which could show effects missed by single-gene models.'
article_number: e1007642
article_processing_charge: No
article_type: original
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Tamar
full_name: Friedlander, Tamar
last_name: Friedlander
citation:
ama: Grah R, Friedlander T. The relation between crosstalk and gene regulation form
revisited. PLOS Computational Biology. 2020;16(2). doi:10.1371/journal.pcbi.1007642
apa: Grah, R., & Friedlander, T. (2020). The relation between crosstalk and
gene regulation form revisited. PLOS Computational Biology. Public Library
of Science. https://doi.org/10.1371/journal.pcbi.1007642
chicago: Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene
Regulation Form Revisited.” PLOS Computational Biology. Public Library
of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.
ieee: R. Grah and T. Friedlander, “The relation between crosstalk and gene regulation
form revisited,” PLOS Computational Biology, vol. 16, no. 2. Public Library
of Science, 2020.
ista: Grah R, Friedlander T. 2020. The relation between crosstalk and gene regulation
form revisited. PLOS Computational Biology. 16(2), e1007642.
mla: Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene
Regulation Form Revisited.” PLOS Computational Biology, vol. 16, no. 2,
e1007642, Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642.
short: R. Grah, T. Friedlander, PLOS Computational Biology 16 (2020).
date_created: 2020-03-06T07:39:38Z
date_published: 2020-02-25T00:00:00Z
date_updated: 2026-04-08T07:25:08Z
day: '25'
ddc:
- '000'
- '570'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642
external_id:
isi:
- '000526725200019'
pmid:
- '32097416'
file:
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checksum: 5239dd134dc6e1c71fe7b3ce2953da37
content_type: application/pdf
creator: dernst
date_created: 2020-03-09T15:12:21Z
date_updated: 2020-07-14T12:48:00Z
file_id: '7579'
file_name: 2020_PlosCompBio_Grah.pdf
file_size: 2209325
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file_date_updated: 2020-07-14T12:48:00Z
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intvolume: ' 16'
isi: 1
issue: '2'
language:
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month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: PLOS Computational Biology
publication_identifier:
issn:
- 1553-7358
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
record:
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relation: research_data
status: deleted
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relation: research_data
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- id: '9777'
relation: research_data
status: public
- id: '8155'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: The relation between crosstalk and gene regulation form revisited
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2020'
...
---
_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'
...
---
OA_place: publisher
_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:10.15479/AT:ISTA:8155
apa: Grah, R. (2020). Gene regulation across scales – how biophysical constraints
shape evolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8155
chicago: Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints
Shape Evolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8155.
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. Gene Regulation across Scales – How Biophysical Constraints Shape
Evolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8155.
short: R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape
Evolution, Institute of Science and Technology Austria, 2020.
corr_author: '1'
date_created: 2020-07-23T09:51:28Z
date_published: 2020-07-24T00:00:00Z
date_updated: 2026-04-08T07:25:09Z
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
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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: ba8df636-2132-11f1-aed0-ed93e2281fdd
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: '8951'
abstract:
- lang: eng
text: Gene expression levels are influenced by multiple coexisting molecular mechanisms.
Some of these interactions, such as those of transcription factors and promoters
have been studied extensively. However, predicting phenotypes of gene regulatory
networks remains a major challenge. Here, we use a well-defined synthetic gene
regulatory network to study how network phenotypes depend on local genetic context,
i.e. the genetic neighborhood of a transcription factor and its relative position.
We show that one gene regulatory network with fixed topology can display not only
quantitatively but also qualitatively different phenotypes, depending solely on
the local genetic context of its components. Our results demonstrate that changes
in local genetic context can place a single transcriptional unit within two separate
regulons without the need for complex regulatory sequences. We propose that relative
order of individual transcriptional units, with its potential for combinatorial
complexity, plays an important role in shaping phenotypes of gene regulatory networks.
article_processing_charge: No
author:
- first_name: Anna A
full_name: Nagy-Staron, Anna A
id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
last_name: Nagy-Staron
orcid: 0000-0002-1391-8377
citation:
ama: Nagy-Staron AA. Sequences of gene regulatory network permutations for the article
“Local genetic context shapes the function of a gene regulatory network.” 2020.
doi:10.15479/AT:ISTA:8951
apa: Nagy-Staron, A. A. (2020). Sequences of gene regulatory network permutations
for the article “Local genetic context shapes the function of a gene regulatory
network.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8951
chicago: Nagy-Staron, Anna A. “Sequences of Gene Regulatory Network Permutations
for the Article ‘Local Genetic Context Shapes the Function of a Gene Regulatory
Network.’” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8951.
ieee: A. A. Nagy-Staron, “Sequences of gene regulatory network permutations for
the article ‘Local genetic context shapes the function of a gene regulatory network.’”
Institute of Science and Technology Austria, 2020.
ista: Nagy-Staron AA. 2020. Sequences of gene regulatory network permutations for
the article ‘Local genetic context shapes the function of a gene regulatory network’,
Institute of Science and Technology Austria, 10.15479/AT:ISTA:8951.
mla: Nagy-Staron, Anna A. Sequences of Gene Regulatory Network Permutations for
the Article “Local Genetic Context Shapes the Function of a Gene Regulatory Network.”
Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8951.
short: A.A. Nagy-Staron, (2020).
contributor:
- contributor_type: project_member
first_name: Anna A
id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
last_name: Nagy-Staron
- contributor_type: project_member
first_name: Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
- contributor_type: project_member
first_name: Caroline
last_name: Caruso Carter
- contributor_type: project_member
first_name: Elisabeth
last_name: Sonnleitner
- contributor_type: project_member
first_name: Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- contributor_type: project_member
first_name: Tiago
last_name: Paixão
- contributor_type: project_manager
first_name: Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
corr_author: '1'
date_created: 2020-12-20T10:00:26Z
date_published: 2020-12-21T00:00:00Z
date_updated: 2025-06-12T06:36:16Z
day: '21'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:8951
file:
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checksum: f57862aeee1690c7effd2b1117d40ed1
content_type: text/plain
creator: bkavcic
date_created: 2020-12-20T09:52:52Z
date_updated: 2020-12-20T09:52:52Z
file_id: '8952'
file_name: readme.txt
file_size: 523
relation: main_file
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checksum: f2c6d5232ec6d551b6993991e8689e9f
content_type: application/octet-stream
creator: bkavcic
date_created: 2020-12-20T22:01:44Z
date_updated: 2020-12-20T22:01:44Z
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file_name: GRNs Research depository.gb
file_size: 379228
relation: main_file
success: 1
file_date_updated: 2020-12-20T22:01:44Z
has_accepted_license: '1'
keyword:
- Gene regulatory networks
- Gene expression
- Escherichia coli
- Synthetic Biology
month: '12'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '9283'
relation: used_in_publication
status: public
status: public
title: Sequences of gene regulatory network permutations for the article "Local genetic
context shapes the function of a gene regulatory network"
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: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_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:
- _id: CaGu
- _id: GaTk
doi: 10.15479/AT:ISTA:7383
file:
- access_level: open_access
checksum: 9d292cf5207b3829225f44c044cdb3fd
content_type: application/zip
creator: rgrah
date_created: 2020-01-28T10:39:40Z
date_updated: 2020-07-14T12:47:57Z
file_id: '7384'
file_name: Scripts.zip
file_size: 73363365
relation: main_file
- access_level: open_access
checksum: 4076ceab32ef588cc233802bab24c1ab
content_type: text/plain
creator: rgrah
date_created: 2020-01-28T10:39:30Z
date_updated: 2020-07-14T12:47:57Z
file_id: '7385'
file_name: READ_ME_MAIN.txt
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
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
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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: 2026-06-24T22:31:02Z
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
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: 2026-06-18T18:17:35Z
day: '19'
ddc:
- '500'
- '570'
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'
...