---
_id: '7490'
abstract:
- lang: eng
text: In plants, clathrin mediated endocytosis (CME) represents the major route
for cargo internalisation from the cell surface. It has been assumed to operate
in an evolutionary conserved manner as in yeast and animals. Here we report characterisation
of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement
in electron microscopy and quantitative live imaging techniques. Arabidopsis CME
appears to follow the constant curvature model and the bona fide CME population
generates vesicles of a predominantly hexagonal-basket type; larger and with faster
kinetics than in other models. Contrary to the existing paradigm, actin is dispensable
for CME events at the plasma membrane but plays a unique role in collecting endocytic
vesicles, sorting of internalised cargos and directional endosome movement that
itself actively promote CME events. Internalized vesicles display a strongly delayed
and sequential uncoating. These unique features highlight the independent evolution
of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
article_number: e52067
article_processing_charge: No
article_type: original
author:
- first_name: Madhumitha
full_name: Narasimhan, Madhumitha
id: 44BF24D0-F248-11E8-B48F-1D18A9856A87
last_name: Narasimhan
orcid: 0000-0002-8600-0671
- first_name: Alexander J
full_name: Johnson, Alexander J
id: 46A62C3A-F248-11E8-B48F-1D18A9856A87
last_name: Johnson
orcid: 0000-0002-2739-8843
- first_name: Roshan
full_name: Prizak, Roshan
id: 4456104E-F248-11E8-B48F-1D18A9856A87
last_name: Prizak
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Shutang
full_name: Tan, Shutang
id: 2DE75584-F248-11E8-B48F-1D18A9856A87
last_name: Tan
orcid: 0000-0002-0471-8285
- first_name: Barbara E
full_name: Casillas Perez, Barbara E
id: 351ED2AA-F248-11E8-B48F-1D18A9856A87
last_name: Casillas Perez
- first_name: Jiří
full_name: Friml, Jiří
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
citation:
ama: Narasimhan M, Johnson AJ, Prizak R, et al. Evolutionarily unique mechanistic
framework of clathrin-mediated endocytosis in plants. eLife. 2020;9. doi:10.7554/eLife.52067
apa: Narasimhan, M., Johnson, A. J., Prizak, R., Kaufmann, W., Tan, S., Casillas
Perez, B. E., & Friml, J. (2020). Evolutionarily unique mechanistic framework
of clathrin-mediated endocytosis in plants. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.52067
chicago: Narasimhan, Madhumitha, Alexander J Johnson, Roshan Prizak, Walter Kaufmann,
Shutang Tan, Barbara E Casillas Perez, and Jiří Friml. “Evolutionarily Unique
Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” ELife.
eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.52067.
ieee: M. Narasimhan et al., “Evolutionarily unique mechanistic framework
of clathrin-mediated endocytosis in plants,” eLife, vol. 9. eLife Sciences
Publications, 2020.
ista: Narasimhan M, Johnson AJ, Prizak R, Kaufmann W, Tan S, Casillas Perez BE,
Friml J. 2020. Evolutionarily unique mechanistic framework of clathrin-mediated
endocytosis in plants. eLife. 9, e52067.
mla: Narasimhan, Madhumitha, et al. “Evolutionarily Unique Mechanistic Framework
of Clathrin-Mediated Endocytosis in Plants.” ELife, vol. 9, e52067, eLife
Sciences Publications, 2020, doi:10.7554/eLife.52067.
short: M. Narasimhan, A.J. Johnson, R. Prizak, W. Kaufmann, S. Tan, B.E. Casillas
Perez, J. Friml, ELife 9 (2020).
date_created: 2020-02-16T23:00:50Z
date_published: 2020-01-23T00:00:00Z
date_updated: 2023-08-18T06:33:07Z
day: '23'
ddc:
- '570'
- '580'
department:
- _id: JiFr
- _id: GaTk
- _id: EM-Fac
- _id: SyCr
doi: 10.7554/eLife.52067
ec_funded: 1
external_id:
isi:
- '000514104100001'
pmid:
- '31971511'
file:
- access_level: open_access
checksum: 2052daa4be5019534f3a42f200a09f32
content_type: application/pdf
creator: dernst
date_created: 2020-02-18T07:21:16Z
date_updated: 2020-07-14T12:47:59Z
file_id: '7494'
file_name: 2020_eLife_Narasimhan.pdf
file_size: 7247468
relation: main_file
file_date_updated: 2020-07-14T12:47:59Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742985'
name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 26538374-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03630
name: Molecular mechanisms of endocytic cargo recognition in plants
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis
in plants
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 9
year: '2020'
...
---
_id: '9779'
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: Tamar
full_name: Friedlander, Tamar
last_name: Friedlander
citation:
ama: Grah R, Friedlander T. Distribution of crosstalk values. 2020. doi:10.1371/journal.pcbi.1007642.s003
apa: Grah, R., & Friedlander, T. (2020). Distribution of crosstalk values. Public
Library of Science. https://doi.org/10.1371/journal.pcbi.1007642.s003
chicago: Grah, Rok, and Tamar Friedlander. “Distribution of Crosstalk Values.” Public
Library of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s003.
ieee: R. Grah and T. Friedlander, “Distribution of crosstalk values.” Public Library
of Science, 2020.
ista: Grah R, Friedlander T. 2020. Distribution of crosstalk values, Public Library
of Science, 10.1371/journal.pcbi.1007642.s003.
mla: Grah, Rok, and Tamar Friedlander. Distribution of Crosstalk Values.
Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642.s003.
short: R. Grah, T. Friedlander, (2020).
date_created: 2021-08-06T07:24:37Z
date_published: 2020-02-25T00:00:00Z
date_updated: 2023-08-18T06:47:47Z
day: '25'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642.s003
month: '02'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '7569'
relation: research_data
status: public
status: public
title: Distribution of crosstalk values
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2020'
...
---
_id: '9776'
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: Tamar
full_name: Friedlander, Tamar
last_name: Friedlander
citation:
ama: Grah R, Friedlander T. Supporting information. 2020. doi:10.1371/journal.pcbi.1007642.s001
apa: Grah, R., & Friedlander, T. (2020). Supporting information. Public Library
of Science. https://doi.org/10.1371/journal.pcbi.1007642.s001
chicago: Grah, Rok, and Tamar Friedlander. “Supporting Information.” Public Library
of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s001.
ieee: R. Grah and T. Friedlander, “Supporting information.” Public Library of Science,
2020.
ista: Grah R, Friedlander T. 2020. Supporting information, Public Library of Science,
10.1371/journal.pcbi.1007642.s001.
mla: Grah, Rok, and Tamar Friedlander. Supporting Information. Public Library
of Science, 2020, doi:10.1371/journal.pcbi.1007642.s001.
short: R. Grah, T. Friedlander, (2020).
date_created: 2021-08-06T07:15:04Z
date_published: 2020-02-25T00:00:00Z
date_updated: 2023-08-18T06:47:47Z
day: '25'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642.s001
month: '02'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '7569'
relation: used_in_publication
status: public
status: public
title: Supporting information
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2020'
...
---
_id: '7656'
abstract:
- lang: eng
text: 'We propose that correlations among neurons are generically strong enough
to organize neural activity patterns into a discrete set of clusters, which can
each be viewed as a population codeword. Our reasoning starts with the analysis
of retinal ganglion cell data using maximum entropy models, showing that the population
is robustly in a frustrated, marginally sub-critical, or glassy, state. This leads
to an argument that neural populations in many other brain areas might share this
structure. Next, we use latent variable models to show that this glassy state
possesses well-defined clusters of neural activity. Clusters have three appealing
properties: (i) clusters exhibit error correction, i.e., they are reproducibly
elicited by the same stimulus despite variability at the level of constituent
neurons; (ii) clusters encode qualitatively different visual features than their
constituent neurons; and (iii) clusters can be learned by downstream neural circuits
in an unsupervised fashion. We hypothesize that these properties give rise to
a “learnable” neural code which the cortical hierarchy uses to extract increasingly
complex features without supervision or reinforcement.'
article_number: '20'
article_processing_charge: No
article_type: original
author:
- first_name: Michael J.
full_name: Berry, Michael J.
last_name: Berry
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: 'Berry MJ, Tkačik G. Clustering of neural activity: A design principle for
population codes. Frontiers in Computational Neuroscience. 2020;14. doi:10.3389/fncom.2020.00020'
apa: 'Berry, M. J., & Tkačik, G. (2020). Clustering of neural activity: A design
principle for population codes. Frontiers in Computational Neuroscience.
Frontiers. https://doi.org/10.3389/fncom.2020.00020'
chicago: 'Berry, Michael J., and Gašper Tkačik. “Clustering of Neural Activity:
A Design Principle for Population Codes.” Frontiers in Computational Neuroscience.
Frontiers, 2020. https://doi.org/10.3389/fncom.2020.00020.'
ieee: 'M. J. Berry and G. Tkačik, “Clustering of neural activity: A design principle
for population codes,” Frontiers in Computational Neuroscience, vol. 14.
Frontiers, 2020.'
ista: 'Berry MJ, Tkačik G. 2020. Clustering of neural activity: A design principle
for population codes. Frontiers in Computational Neuroscience. 14, 20.'
mla: 'Berry, Michael J., and Gašper Tkačik. “Clustering of Neural Activity: A Design
Principle for Population Codes.” Frontiers in Computational Neuroscience,
vol. 14, 20, Frontiers, 2020, doi:10.3389/fncom.2020.00020.'
short: M.J. Berry, G. Tkačik, Frontiers in Computational Neuroscience 14 (2020).
date_created: 2020-04-12T22:00:40Z
date_published: 2020-03-13T00:00:00Z
date_updated: 2023-08-18T10:30:11Z
day: '13'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.3389/fncom.2020.00020
external_id:
isi:
- '000525543200001'
pmid:
- '32231528'
file:
- access_level: open_access
checksum: 2b1da23823eae9cedbb42d701945b61e
content_type: application/pdf
creator: dernst
date_created: 2020-04-14T12:20:39Z
date_updated: 2020-07-14T12:48:01Z
file_id: '7659'
file_name: 2020_Frontiers_Berry.pdf
file_size: 4082937
relation: main_file
file_date_updated: 2020-07-14T12:48:01Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Computational Neuroscience
publication_identifier:
eissn:
- '16625188'
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Clustering of neural activity: A design principle for population codes'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 14
year: '2020'
...
---
_id: '8698'
abstract:
- lang: eng
text: The brain represents and reasons probabilistically about complex stimuli and
motor actions using a noisy, spike-based neural code. A key building block for
such neural computations, as well as the basis for supervised and unsupervised
learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional
neural activity patterns. Despite progress in statistical modeling of neural responses
and deep learning, current approaches either do not scale to large neural populations
or cannot be implemented using biologically realistic mechanisms. Inspired by
the sparse and random connectivity of real neuronal circuits, we present a model
for neural codes that accurately estimates the likelihood of individual spiking
patterns and has a straightforward, scalable, efficient, learnable, and realistic
neural implementation. This model’s performance on simultaneously recorded spiking
activity of >100 neurons in the monkey visual and prefrontal cortices is comparable
with or better than that of state-of-the-art models. Importantly, the model can
be learned using a small number of samples and using a local learning rule that
utilizes noise intrinsic to neural circuits. Slower, structural changes in random
connectivity, consistent with rewiring and pruning processes, further improve
the efficiency and sparseness of the resulting neural representations. Our results
merge insights from neuroanatomy, machine learning, and theoretical neuroscience
to suggest random sparse connectivity as a key design principle for neuronal computation.
acknowledgement: We thank Udi Karpas, Roy Harpaz, Tal Tamir, Adam Haber, and Amir
Bar for discussions and suggestions; and especially Oren Forkosh and Walter Senn
for invaluable discussions of the learning rule. This work was supported by European
Research Council Grant 311238 (to E.S.) and Israel Science Foundation Grant 1629/12
(to E.S.); as well as research support from Martin Kushner Schnur and Mr. and Mrs.
Lawrence Feis (E.S.); National Institute of Mental Health Grant R01MH109180 (to
R.K.); a Pew Scholarship in Biomedical Sciences (to R.K.); Simons Collaboration
on the Global Brain Grant 542997 (to R.K. and E.S.); and a CRCNS (Collaborative
Research in Computational Neuroscience) grant (to R.K. and E.S.).
article_processing_charge: No
article_type: original
author:
- first_name: Ori
full_name: Maoz, Ori
last_name: Maoz
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Mohamad Saleh
full_name: Esteki, Mohamad Saleh
last_name: Esteki
- first_name: Roozbeh
full_name: Kiani, Roozbeh
last_name: Kiani
- first_name: Elad
full_name: Schneidman, Elad
last_name: Schneidman
citation:
ama: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. Learning probabilistic
neural representations with randomly connected circuits. Proceedings of the
National Academy of Sciences of the United States of America. 2020;117(40):25066-25073.
doi:10.1073/pnas.1912804117
apa: Maoz, O., Tkačik, G., Esteki, M. S., Kiani, R., & Schneidman, E. (2020).
Learning probabilistic neural representations with randomly connected circuits.
Proceedings of the National Academy of Sciences of the United States of America.
National Academy of Sciences. https://doi.org/10.1073/pnas.1912804117
chicago: Maoz, Ori, Gašper Tkačik, Mohamad Saleh Esteki, Roozbeh Kiani, and Elad
Schneidman. “Learning Probabilistic Neural Representations with Randomly Connected
Circuits.” Proceedings of the National Academy of Sciences of the United States
of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1912804117.
ieee: O. Maoz, G. Tkačik, M. S. Esteki, R. Kiani, and E. Schneidman, “Learning probabilistic
neural representations with randomly connected circuits,” Proceedings of the
National Academy of Sciences of the United States of America, vol. 117, no.
40. National Academy of Sciences, pp. 25066–25073, 2020.
ista: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. 2020. Learning probabilistic
neural representations with randomly connected circuits. Proceedings of the National
Academy of Sciences of the United States of America. 117(40), 25066–25073.
mla: Maoz, Ori, et al. “Learning Probabilistic Neural Representations with Randomly
Connected Circuits.” Proceedings of the National Academy of Sciences of the
United States of America, vol. 117, no. 40, National Academy of Sciences,
2020, pp. 25066–73, doi:10.1073/pnas.1912804117.
short: O. Maoz, G. Tkačik, M.S. Esteki, R. Kiani, E. Schneidman, Proceedings of
the National Academy of Sciences of the United States of America 117 (2020) 25066–25073.
date_created: 2020-10-25T23:01:16Z
date_published: 2020-10-06T00:00:00Z
date_updated: 2023-08-22T12:11:23Z
day: '06'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1073/pnas.1912804117
external_id:
isi:
- '000579045200012'
pmid:
- '32948691'
file:
- access_level: open_access
checksum: c6a24fdecf3f28faf447078e7a274a88
content_type: application/pdf
creator: cziletti
date_created: 2020-10-27T14:57:50Z
date_updated: 2020-10-27T14:57:50Z
file_id: '8713'
file_name: 2020_PNAS_Maoz.pdf
file_size: 1755359
relation: main_file
success: 1
file_date_updated: 2020-10-27T14:57:50Z
has_accepted_license: '1'
intvolume: ' 117'
isi: 1
issue: '40'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '10'
oa: 1
oa_version: Published Version
page: 25066-25073
pmid: 1
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Learning probabilistic neural representations with randomly connected circuits
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: 117
year: '2020'
...
---
_id: '8955'
abstract:
- lang: eng
text: Skeletal muscle activity is continuously modulated across physiologic states
to provide coordination, flexibility and responsiveness to body tasks and external
inputs. Despite the central role the muscular system plays in facilitating vital
body functions, the network of brain-muscle interactions required to control hundreds
of muscles and synchronize their activation in relation to distinct physiologic
states has not been investigated. Recent approaches have focused on general associations
between individual brain rhythms and muscle activation during movement tasks.
However, the specific forms of coupling, the functional network of cortico-muscular
coordination, and how network structure and dynamics are modulated by autonomic
regulation across physiologic states remains unknown. To identify and quantify
the cortico-muscular interaction network and uncover basic features of neuro-autonomic
control of muscle function, we investigate the coupling between synchronous bursts
in cortical rhythms and peripheral muscle activation during sleep and wake. Utilizing
the concept of time delay stability and a novel network physiology approach, we
find that the brain-muscle network exhibits complex dynamic patterns of communication
involving multiple brain rhythms across cortical locations and different electromyographic
frequency bands. Moreover, our results show that during each physiologic state
the cortico-muscular network is characterized by a specific profile of network
links strength, where particular brain rhythms play role of main mediators of
interaction and control. Further, we discover a hierarchical reorganization in
network structure across physiologic states, with high connectivity and network
link strength during wake, intermediate during REM and light sleep, and low during
deep sleep, a sleep-stage stratification that demonstrates a unique association
between physiologic states and cortico-muscular network structure. The reported
empirical observations are consistent across individual subjects, indicating universal
behavior in network structure and dynamics, and high sensitivity of cortico-muscular
control to changes in autonomic regulation, even at low levels of physical activity
and muscle tone during sleep. Our findings demonstrate previously unrecognized
basic principles of brain-muscle network communication and control, and provide
new perspectives on the regulatory mechanisms of brain dynamics and locomotor
activation, with potential clinical implications for neurodegenerative, movement
and sleep disorders, and for developing efficient treatment strategies.
acknowledgement: We acknowledge support from the W. M. Keck Foundation, National Institutes
of Health (NIH Grant 1R01-HL098437), the US-Israel Binational Science Foundation
(BSF Grant 2012219), and the Office of Naval Research (ONR Grant 000141010078).
FL acknowledges support also from the European Union's Horizon 2020 research and
innovation program under the Marie Sklodowska-Curie Grant Agreement No. 754411.
article_number: '558070'
article_processing_charge: No
article_type: original
author:
- first_name: Rossella
full_name: Rizzo, Rossella
last_name: Rizzo
- first_name: Xiyun
full_name: Zhang, Xiyun
last_name: Zhang
- first_name: Jilin W.J.L.
full_name: Wang, Jilin W.J.L.
last_name: Wang
- first_name: Fabrizio
full_name: Lombardi, Fabrizio
id: A057D288-3E88-11E9-986D-0CF4E5697425
last_name: Lombardi
orcid: 0000-0003-2623-5249
- first_name: Plamen Ch
full_name: Ivanov, Plamen Ch
last_name: Ivanov
citation:
ama: Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. Network physiology of cortico–muscular
interactions. Frontiers in Physiology. 2020;11. doi:10.3389/fphys.2020.558070
apa: Rizzo, R., Zhang, X., Wang, J. W. J. L., Lombardi, F., & Ivanov, P. C.
(2020). Network physiology of cortico–muscular interactions. Frontiers in Physiology.
Frontiers. https://doi.org/10.3389/fphys.2020.558070
chicago: Rizzo, Rossella, Xiyun Zhang, Jilin W.J.L. Wang, Fabrizio Lombardi, and
Plamen Ch Ivanov. “Network Physiology of Cortico–Muscular Interactions.” Frontiers
in Physiology. Frontiers, 2020. https://doi.org/10.3389/fphys.2020.558070.
ieee: R. Rizzo, X. Zhang, J. W. J. L. Wang, F. Lombardi, and P. C. Ivanov, “Network
physiology of cortico–muscular interactions,” Frontiers in Physiology,
vol. 11. Frontiers, 2020.
ista: Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. 2020. Network physiology
of cortico–muscular interactions. Frontiers in Physiology. 11, 558070.
mla: Rizzo, Rossella, et al. “Network Physiology of Cortico–Muscular Interactions.”
Frontiers in Physiology, vol. 11, 558070, Frontiers, 2020, doi:10.3389/fphys.2020.558070.
short: R. Rizzo, X. Zhang, J.W.J.L. Wang, F. Lombardi, P.C. Ivanov, Frontiers in
Physiology 11 (2020).
date_created: 2020-12-20T23:01:18Z
date_published: 2020-11-26T00:00:00Z
date_updated: 2023-08-24T11:00:45Z
day: '26'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.3389/fphys.2020.558070
ec_funded: 1
external_id:
isi:
- '000596849400001'
pmid:
- '33324233'
file:
- access_level: open_access
checksum: ef9515b28c5619b7126c0f347958bcb3
content_type: application/pdf
creator: dernst
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oa_version: Published Version
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Frontiers in Physiology
publication_identifier:
eissn:
- 1664042X
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: Network physiology of cortico–muscular interactions
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2020'
...
---
_id: '9000'
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 biophysical 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 nonequilibrium
models, progress is difficult due to an explosion in the number of parameters.
Here, we navigate this complexity by looking for minimal nonequilibrium 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
nonequilibrium models is in a trade-off with gene-expression noise, predicting
bursty dynamics—an experimentally observed hallmark of eukaryotic transcription.
By drastically reducing the vast parameter space of nonequilibrium enhancer models
to a much smaller subspace that optimally realizes biological function, we deliver
a rich class of models that could be tractably inferred from data in the near
future.'
acknowledgement: G.T. was supported by Human Frontiers Science Program Grant RGP0034/2018.
R.G. was supported by the Austrian Academy of Sciences DOC Fellowship. R.G. thanks
S. Avvakumov for helpful discussions.
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: 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. Nonequilibrium models of optimal enhancer function.
PNAS. 2020;117(50):31614-31622. doi:10.1073/pnas.2006731117
apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Nonequilibrium models of optimal
enhancer function. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2006731117
chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Nonequilibrium Models of
Optimal Enhancer Function.” PNAS. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2006731117.
ieee: R. Grah, B. Zoller, and G. Tkačik, “Nonequilibrium models of optimal enhancer
function,” PNAS, vol. 117, no. 50. National Academy of Sciences, pp. 31614–31622,
2020.
ista: Grah R, Zoller B, Tkačik G. 2020. Nonequilibrium models of optimal enhancer
function. PNAS. 117(50), 31614–31622.
mla: Grah, Rok, et al. “Nonequilibrium Models of Optimal Enhancer Function.” PNAS,
vol. 117, no. 50, National Academy of Sciences, 2020, pp. 31614–22, doi:10.1073/pnas.2006731117.
short: R. Grah, B. Zoller, G. Tkačik, PNAS 117 (2020) 31614–31622.
date_created: 2021-01-10T23:01:17Z
date_published: 2020-12-15T00:00:00Z
date_updated: 2023-08-24T11:10:22Z
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ddc:
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department:
- _id: GaTk
doi: 10.1073/pnas.2006731117
external_id:
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pmid:
- '33268497'
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page: 31614-31622
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- _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: PNAS
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/new-compact-model-for-gene-regulation-in-higher-organisms/
scopus_import: '1'
status: public
title: Nonequilibrium models of optimal enhancer function
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: 117
year: '2020'
...
---
_id: '8084'
abstract:
- lang: eng
text: Origin and functions of intermittent transitions among sleep stages, including
brief awakenings and arousals, constitute a challenge to the current homeostatic
framework for sleep regulation, focusing on factors modulating sleep over large
time scales. Here we propose that the complex micro-architecture characterizing
sleep on scales of seconds and minutes results from intrinsic non-equilibrium
critical dynamics. We investigate θ- and δ-wave dynamics in control rats and in
rats where the sleep-promoting ventrolateral preoptic nucleus (VLPO) is lesioned
(male Sprague-Dawley rats). We demonstrate that bursts in θ and δ cortical rhythms
exhibit complex temporal organization, with long-range correlations and robust
duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts,
quiescent phase) duration distributions, features typical of non-equilibrium systems
self-organizing at criticality. We show that such non-equilibrium behavior relates
to anti-correlated coupling between θ- and δ-bursts, persists across a range of
time scales, and is independent of the dominant physiologic state; indications
of a basic principle in sleep regulation. Further, we find that VLPO lesions lead
to a modulation of cortical dynamics resulting in altered dynamical parameters
of θ- and δ-bursts and significant reduction in θ–δ coupling. Our empirical findings
and model simulations demonstrate that θ–δ coupling is essential for the emerging
non-equilibrium critical dynamics observed across the sleep–wake cycle, and indicate
that VLPO neurons may have dual role for both sleep and arousal/brief wake activation.
The uncovered critical behavior in sleep- and wake-related cortical rhythms indicates
a mechanism essential for the micro-architecture of spontaneous sleep-stage and
arousal transitions within a novel, non-homeostatic paradigm of sleep regulation.
article_processing_charge: No
article_type: original
author:
- first_name: Fabrizio
full_name: Lombardi, Fabrizio
id: A057D288-3E88-11E9-986D-0CF4E5697425
last_name: Lombardi
orcid: 0000-0003-2623-5249
- first_name: Manuel
full_name: Gómez-Extremera, Manuel
last_name: Gómez-Extremera
- first_name: Pedro
full_name: Bernaola-Galván, Pedro
last_name: Bernaola-Galván
- first_name: Ramalingam
full_name: Vetrivelan, Ramalingam
last_name: Vetrivelan
- first_name: Clifford B.
full_name: Saper, Clifford B.
last_name: Saper
- first_name: Thomas E.
full_name: Scammell, Thomas E.
last_name: Scammell
- first_name: Plamen Ch.
full_name: Ivanov, Plamen Ch.
last_name: Ivanov
citation:
ama: Lombardi F, Gómez-Extremera M, Bernaola-Galván P, et al. Critical dynamics
and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism
for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake.
Journal of Neuroscience. 2020;40(1):171-190. doi:10.1523/jneurosci.1278-19.2019
apa: Lombardi, F., Gómez-Extremera, M., Bernaola-Galván, P., Vetrivelan, R., Saper,
C. B., Scammell, T. E., & Ivanov, P. C. (2020). Critical dynamics and coupling
in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage
transitions and dual role of VLPO neurons in both sleep and wake. Journal of
Neuroscience. Society for Neuroscience. https://doi.org/10.1523/jneurosci.1278-19.2019
chicago: Lombardi, Fabrizio, Manuel Gómez-Extremera, Pedro Bernaola-Galván, Ramalingam
Vetrivelan, Clifford B. Saper, Thomas E. Scammell, and Plamen Ch. Ivanov. “Critical
Dynamics and Coupling in Bursts of Cortical Rhythms Indicate Non-Homeostatic Mechanism
for Sleep-Stage Transitions and Dual Role of VLPO Neurons in Both Sleep and Wake.”
Journal of Neuroscience. Society for Neuroscience, 2020. https://doi.org/10.1523/jneurosci.1278-19.2019.
ieee: F. Lombardi et al., “Critical dynamics and coupling in bursts of cortical
rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual
role of VLPO neurons in both sleep and wake,” Journal of Neuroscience,
vol. 40, no. 1. Society for Neuroscience, pp. 171–190, 2020.
ista: Lombardi F, Gómez-Extremera M, Bernaola-Galván P, Vetrivelan R, Saper CB,
Scammell TE, Ivanov PC. 2020. Critical dynamics and coupling in bursts of cortical
rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual
role of VLPO neurons in both sleep and wake. Journal of Neuroscience. 40(1), 171–190.
mla: Lombardi, Fabrizio, et al. “Critical Dynamics and Coupling in Bursts of Cortical
Rhythms Indicate Non-Homeostatic Mechanism for Sleep-Stage Transitions and Dual
Role of VLPO Neurons in Both Sleep and Wake.” Journal of Neuroscience,
vol. 40, no. 1, Society for Neuroscience, 2020, pp. 171–90, doi:10.1523/jneurosci.1278-19.2019.
short: F. Lombardi, M. Gómez-Extremera, P. Bernaola-Galván, R. Vetrivelan, C.B.
Saper, T.E. Scammell, P.C. Ivanov, Journal of Neuroscience 40 (2020) 171–190.
date_created: 2020-07-05T15:24:51Z
date_published: 2020-01-02T00:00:00Z
date_updated: 2023-09-05T14:02:55Z
day: '02'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1523/jneurosci.1278-19.2019
ec_funded: 1
external_id:
isi:
- '000505167600016'
pmid:
- '31694962'
file:
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content_type: application/pdf
creator: dernst
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date_updated: 2020-07-22T11:44:48Z
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page: 171-190
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call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Journal of Neuroscience
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eissn:
- 1529-2401
issn:
- 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic
mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep
and wake
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 40
year: '2020'
...
---
_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.
date_created: 2020-07-23T09:51:28Z
date_published: 2020-07-24T00:00:00Z
date_updated: 2023-09-07T13:13:27Z
day: '24'
ddc:
- '530'
- '570'
degree_awarded: PhD
department:
- _id: CaGu
- _id: GaTk
doi: 10.15479/AT:ISTA:8155
file:
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content_type: application/pdf
creator: rgrah
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month: '07'
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page: '310'
project:
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name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7675'
relation: part_of_dissertation
status: public
- id: '7569'
relation: part_of_dissertation
status: public
- id: '7652'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
title: Gene regulation across scales – how biophysical constraints shape evolution
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '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).
date_created: 2020-04-23T10:12:51Z
date_published: 2020-04-09T00:00:00Z
date_updated: 2023-09-07T13:13:26Z
day: '09'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1101/2020.04.08.029405
language:
- iso: eng
main_file_link:
- open_access: '1'
url: 'https://doi.org/10.1101/2020.04.08.029405 '
month: '04'
oa: 1
oa_version: Preprint
project:
- _id: 2665AAFE-B435-11E9-9278-68D0E5697425
grant_number: RGP0034/2018
name: Can evolution minimize spurious signaling crosstalk to reach optimal performance?
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication: bioRxiv
publication_status: published
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '8155'
relation: dissertation_contains
status: public
status: public
title: Normative models of enhancer function
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '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: 2023-09-12T11:02:24Z
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ddc:
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- '570'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642
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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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
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year: '2020'
...
---
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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. Maximizing crosstalk. 2020. doi:10.1371/journal.pcbi.1007642.s002
apa: Grah, R., & Friedlander, T. (2020). Maximizing crosstalk. Public Library
of Science. https://doi.org/10.1371/journal.pcbi.1007642.s002
chicago: Grah, Rok, and Tamar Friedlander. “Maximizing Crosstalk.” Public Library
of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s002.
ieee: R. Grah and T. Friedlander, “Maximizing crosstalk.” Public Library of Science,
2020.
ista: Grah R, Friedlander T. 2020. Maximizing crosstalk, Public Library of Science,
10.1371/journal.pcbi.1007642.s002.
mla: Grah, Rok, and Tamar Friedlander. Maximizing Crosstalk. Public Library
of Science, 2020, doi:10.1371/journal.pcbi.1007642.s002.
short: R. Grah, T. Friedlander, (2020).
date_created: 2021-08-06T07:21:51Z
date_published: 2020-02-25T00:00:00Z
date_updated: 2023-09-12T11:02:25Z
day: '25'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642.s002
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title: Maximizing crosstalk
type: research_data_reference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8657'
abstract:
- lang: eng
text: "Synthesis of proteins – translation – is a fundamental process of life. Quantitative
studies anchor translation into the context of bacterial physiology and reveal
several mathematical relationships, called “growth laws,” which capture physiological
feedbacks between protein synthesis and cell growth. Growth laws describe the
dependency of the ribosome abundance as a function of growth rate, which can change
depending on the growth conditions. Perturbations of translation reveal that bacteria
employ a compensatory strategy in which the reduced translation capability results
in increased expression of the translation machinery.\r\nPerturbations of translation
are achieved in various ways; clinically interesting is the application of translation-targeting
antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology
are often poorly understood. Bacterial responses to two or more simultaneously
applied antibiotics are even more puzzling. The combined antibiotic effect determines
the type of drug interaction, which ranges from synergy (the effect is stronger
than expected) to antagonism (the effect is weaker) and suppression (one of the
drugs loses its potency).\r\nIn the first part of this work, we systematically
measure the pairwise interaction network for translation inhibitors that interfere
with different steps in translation. We find that the interactions are surprisingly
diverse and tend to be more antagonistic. To explore the underlying mechanisms,
we begin with a minimal biophysical model of combined antibiotic action. We base
this model on the kinetics of antibiotic uptake and binding together with the
physiological response described by the growth laws. The biophysical model explains
some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn
the second part of this work, we hypothesize that elusive suppressive drug interactions
result from the interplay between ribosomes halted in different stages of translation.
To elucidate this putative mechanism of drug interactions between translation
inhibitors, we generate translation bottlenecks genetically using in- ducible
control of translation factors that regulate well-defined translation cycle steps.
These perturbations accurately mimic antibiotic action and drug interactions,
supporting that the interplay of different translation bottlenecks partially causes
these interactions.\r\nWe extend this approach by varying two translation bottlenecks
simultaneously. This approach reveals the suppression of translocation inhibition
by inhibited translation. We rationalize this effect by modeling dense traffic
of ribosomes that move on transcripts in a translation factor-mediated manner.
This model predicts a dissolution of traffic jams caused by inhibited translocation
when the density of ribosome traffic is reduced by lowered initiation. We base
this model on the growth laws and quantitative relationships between different
translation and growth parameters.\r\nIn the final part of this work, we describe
a set of tools aimed at quantification of physiological and translation parameters.
We further develop a simple model that directly connects the abundance of a translation
factor with the growth rate, which allows us to extract physiological parameters
describing initiation. We demonstrate the development of tools for measuring translation
rate.\r\nThis thesis showcases how a combination of high-throughput growth rate
mea- surements, genetics, and modeling can reveal mechanisms of drug interactions.
Furthermore, by a gradual transition from combinations of antibiotics to precise
genetic interventions, we demonstrated the equivalency between genetic and chemi-
cal perturbations of translation. These findings tile the path for quantitative
studies of antibiotic combinations and illustrate future approaches towards the
quantitative description of translation."
acknowledged_ssus:
- _id: LifeSc
- _id: M-Shop
acknowledgement: I thank Life Science Facilities for their continuous support with
providing top-notch laboratory materials, keeping the devices humming, and coordinating
the repairs and building of custom-designed laboratory equipment with the MIBA Machine
shop.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
citation:
ama: 'Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics
and physiology. 2020. doi:10.15479/AT:ISTA:8657'
apa: 'Kavcic, B. (2020). Perturbations of protein synthesis: from antibiotics
to genetics and physiology. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8657'
chicago: 'Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to
Genetics and Physiology.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8657.'
ieee: 'B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics
and physiology,” Institute of Science and Technology Austria, 2020.'
ista: 'Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics
and physiology. Institute of Science and Technology Austria.'
mla: 'Kavcic, Bor. Perturbations of Protein Synthesis: From Antibiotics to Genetics
and Physiology. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8657.'
short: 'B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics
and Physiology, Institute of Science and Technology Austria, 2020.'
date_created: 2020-10-13T16:46:14Z
date_published: 2020-10-14T00:00:00Z
date_updated: 2023-09-07T13:20:48Z
day: '14'
ddc:
- '571'
- '530'
- '570'
degree_awarded: PhD
department:
- _id: GaTk
doi: 10.15479/AT:ISTA:8657
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date_updated: 2021-10-07T22:30:03Z
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language:
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month: '10'
oa: 1
oa_version: Published Version
page: '271'
publication_identifier:
isbn:
- 978-3-99078-011-4
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
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relation: part_of_dissertation
status: public
- id: '8250'
relation: part_of_dissertation
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status: public
supervisor:
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
title: 'Perturbations of protein synthesis: from antibiotics to genetics and physiology'
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '8250'
abstract:
- lang: eng
text: 'Antibiotics that interfere with translation, when combined, interact in diverse
and difficult-to-predict ways. Here, we explain these interactions by “translation
bottlenecks”: points in the translation cycle where antibiotics block ribosomal
progression. To elucidate the underlying mechanisms of drug interactions between
translation inhibitors, we generate translation bottlenecks genetically using
inducible control of translation factors that regulate well-defined translation
cycle steps. These perturbations accurately mimic antibiotic action and drug interactions,
supporting that the interplay of different translation bottlenecks causes these
interactions. We further show that growth laws, combined with drug uptake and
binding kinetics, enable the direct prediction of a large fraction of observed
interactions, yet fail to predict suppression. However, varying two translation
bottlenecks simultaneously supports that dense traffic of ribosomes and competition
for translation factors account for the previously unexplained suppression. These
results highlight the importance of “continuous epistasis” in bacterial physiology.'
acknowledgement: "We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K.
Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive
comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support,
which rendered this\r\nwork possible. B.K. thanks all members of Guet group for
many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges
the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work.
We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A.
Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This
work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P
27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to
T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.),
and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310
(to T.B.). Open access funding provided by\r\nProjekt DEAL."
article_number: '4013'
article_processing_charge: No
article_type: original
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between
translation-inhibiting antibiotics. Nature Communications. 2020;11. doi:10.1038/s41467-020-17734-z
apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). Mechanisms of drug
interactions between translation-inhibiting antibiotics. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-020-17734-z
chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of
Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications.
Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17734-z.
ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions
between translation-inhibiting antibiotics,” Nature Communications, vol.
11. Springer Nature, 2020.
ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between
translation-inhibiting antibiotics. Nature Communications. 11, 4013.
mla: Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting
Antibiotics.” Nature Communications, vol. 11, 4013, Springer Nature, 2020,
doi:10.1038/s41467-020-17734-z.
short: B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020).
date_created: 2020-08-12T09:13:50Z
date_published: 2020-08-11T00:00:00Z
date_updated: 2024-03-18T23:30:08Z
day: '11'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1038/s41467-020-17734-z
external_id:
isi:
- '000562769300008'
file:
- access_level: open_access
checksum: 986bebb308850a55850028d3d2b5b664
content_type: application/pdf
creator: dernst
date_created: 2020-08-17T07:36:57Z
date_updated: 2020-08-17T07:36:57Z
file_id: '8275'
file_name: 2020_NatureComm_Kavcic.pdf
file_size: 1965672
relation: main_file
success: 1
file_date_updated: 2020-08-17T07:36:57Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
record:
- id: '8657'
relation: dissertation_contains
status: public
status: public
title: Mechanisms of drug interactions between translation-inhibiting 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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2020'
...
---
_id: '7673'
abstract:
- lang: eng
text: Combining drugs can improve the efficacy of treatments. However, predicting
the effect of drug combinations is still challenging. The combined potency of
drugs determines the drug interaction, which is classified as synergistic, additive,
antagonistic, or suppressive. While probabilistic, non-mechanistic models exist,
there is currently no biophysical model that can predict antibiotic interactions.
Here, we present a physiologically relevant model of the combined action of antibiotics
that inhibit protein synthesis by targeting the ribosome. This model captures
the kinetics of antibiotic binding and transport, and uses bacterial growth laws
to predict growth in the presence of antibiotic combinations. We find that this
biophysical model can produce all drug interaction types except suppression. We
show analytically that antibiotics which cannot bind to the ribosome simultaneously
generally act as substitutes for one another, leading to additive drug interactions.
Previously proposed null expectations for higher-order drug interactions follow
as a limiting case of our model. We further extend the model to include the effects
of direct physical or allosteric interactions between individual drugs on the
ribosome. Notably, such direct interactions profoundly change the combined drug
effect, depending on the kinetic parameters of the drugs used. The model makes
additional predictions for the effects of resistance genes on drug interactions
and for interactions between ribosome-targeting antibiotics and antibiotics with
other targets. These findings enhance our understanding of the interplay between
drug action and cell physiology and are a key step toward a general framework
for predicting drug interactions.
article_processing_charge: No
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined
antibiotic action. bioRxiv. 2020. doi:10.1101/2020.04.18.047886
apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). A minimal biophysical
model of combined antibiotic action. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2020.04.18.047886
chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical
Model of Combined Antibiotic Action.” BioRxiv. Cold Spring Harbor Laboratory,
2020. https://doi.org/10.1101/2020.04.18.047886.
ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “A minimal biophysical model of
combined antibiotic action,” bioRxiv. Cold Spring Harbor Laboratory, 2020.
ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined
antibiotic action. bioRxiv, 10.1101/2020.04.18.047886.
mla: Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.”
BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.18.047886.
short: B. Kavcic, G. Tkačik, M.T. Bollenbach, BioRxiv (2020).
date_created: 2020-04-22T08:27:56Z
date_published: 2020-04-18T00:00:00Z
date_updated: 2024-03-18T23:30:08Z
day: '18'
department:
- _id: GaTk
doi: 10.1101/2020.04.18.047886
language:
- iso: eng
main_file_link:
- open_access: '1'
url: 'https://doi.org/10.1101/2020.04.18.047886 '
month: '04'
oa: 1
oa_version: Preprint
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: bioRxiv
publication_status: published
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '8997'
relation: later_version
status: public
- id: '8657'
relation: dissertation_contains
status: public
status: public
title: A minimal biophysical model of combined antibiotic action
type: preprint
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: 2024-03-18T23:30:38Z
day: '01'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.1038/s41559-020-1132-7
external_id:
isi:
- '000519008300005'
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
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: '8155'
relation: dissertation_contains
status: public
- id: '7383'
relation: research_data
status: public
- id: '7016'
relation: research_data
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 4
year: '2020'
...
---
_id: '7552'
abstract:
- lang: eng
text: 'There is increasing evidence that protein binding to specific sites along
DNA can activate the reading out of genetic information without coming into direct
physical contact with the gene. There also is evidence that these distant but
interacting sites are embedded in a liquid droplet of proteins which condenses
out of the surrounding solution. We argue that droplet-mediated interactions can
account for crucial features of gene regulation only if the droplet is poised
at a non-generic point in its phase diagram. We explore a minimal model that embodies
this idea, show that this model has a natural mechanism for self-tuning, and suggest
direct experimental tests. '
article_processing_charge: No
author:
- first_name: William
full_name: Bialek, William
last_name: Bialek
- first_name: Thomas
full_name: Gregor, Thomas
last_name: Gregor
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Bialek W, Gregor T, Tkačik G. Action at a distance in transcriptional regulation.
arXiv:191208579.
apa: Bialek, W., Gregor, T., & Tkačik, G. (n.d.). Action at a distance in transcriptional
regulation. arXiv:1912.08579. ArXiv.
chicago: Bialek, William, Thomas Gregor, and Gašper Tkačik. “Action at a Distance
in Transcriptional Regulation.” ArXiv:1912.08579. ArXiv, n.d.
ieee: W. Bialek, T. Gregor, and G. Tkačik, “Action at a distance in transcriptional
regulation,” arXiv:1912.08579. ArXiv.
ista: Bialek W, Gregor T, Tkačik G. Action at a distance in transcriptional regulation.
arXiv:1912.08579, .
mla: Bialek, William, et al. “Action at a Distance in Transcriptional Regulation.”
ArXiv:1912.08579, ArXiv.
short: W. Bialek, T. Gregor, G. Tkačik, ArXiv:1912.08579 (n.d.).
date_created: 2020-02-28T10:57:08Z
date_published: 2019-12-18T00:00:00Z
date_updated: 2021-01-12T08:14:09Z
day: '18'
department:
- _id: GaTk
external_id:
arxiv:
- '1912.08579'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1912.08579
month: '12'
oa: 1
oa_version: Preprint
page: '5'
project:
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: arXiv:1912.08579
publication_status: submitted
publisher: ArXiv
status: public
title: Action at a distance in transcriptional regulation
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2019'
...
---
_id: '5945'
abstract:
- lang: eng
text: In developing organisms, spatially prescribed cell identities are thought
to be determined by the expression levels of multiple genes. Quantitative tests
of this idea, however, require a theoretical framework capable of exposing the
rules and precision of cell specification over developmental time. We use the
gap gene network in the early fly embryo as an example to show how expression
levels of the four gap genes can be jointly decoded into an optimal specification
of position with 1% accuracy. The decoder correctly predicts, with no free parameters,
the dynamics of pair-rule expression patterns at different developmental time
points and in various mutant backgrounds. Precise cellular identities are thus
available at the earliest stages of development, contrasting the prevailing view
of positional information being slowly refined across successive layers of the
patterning network. Our results suggest that developmental enhancers closely approximate
a mathematically optimal decoding strategy.
article_processing_charge: No
article_type: original
author:
- first_name: Mariela D.
full_name: Petkova, Mariela D.
last_name: Petkova
- first_name: Gasper
full_name: Tkacik, Gasper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkacik
orcid: 0000-0002-6699-1455
- first_name: William
full_name: Bialek, William
last_name: Bialek
- first_name: Eric F.
full_name: Wieschaus, Eric F.
last_name: Wieschaus
- first_name: Thomas
full_name: Gregor, Thomas
last_name: Gregor
citation:
ama: Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. Optimal decoding of
cellular identities in a genetic network. Cell. 2019;176(4):844-855.e15.
doi:10.1016/j.cell.2019.01.007
apa: Petkova, M. D., Tkačik, G., Bialek, W., Wieschaus, E. F., & Gregor, T.
(2019). Optimal decoding of cellular identities in a genetic network. Cell.
Cell Press. https://doi.org/10.1016/j.cell.2019.01.007
chicago: Petkova, Mariela D., Gašper Tkačik, William Bialek, Eric F. Wieschaus,
and Thomas Gregor. “Optimal Decoding of Cellular Identities in a Genetic Network.”
Cell. Cell Press, 2019. https://doi.org/10.1016/j.cell.2019.01.007.
ieee: M. D. Petkova, G. Tkačik, W. Bialek, E. F. Wieschaus, and T. Gregor, “Optimal
decoding of cellular identities in a genetic network,” Cell, vol. 176,
no. 4. Cell Press, p. 844–855.e15, 2019.
ista: Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. 2019. Optimal decoding
of cellular identities in a genetic network. Cell. 176(4), 844–855.e15.
mla: Petkova, Mariela D., et al. “Optimal Decoding of Cellular Identities in a Genetic
Network.” Cell, vol. 176, no. 4, Cell Press, 2019, p. 844–855.e15, doi:10.1016/j.cell.2019.01.007.
short: M.D. Petkova, G. Tkačik, W. Bialek, E.F. Wieschaus, T. Gregor, Cell 176 (2019)
844–855.e15.
date_created: 2019-02-10T22:59:16Z
date_published: 2019-02-07T00:00:00Z
date_updated: 2023-08-24T14:42:47Z
day: '07'
department:
- _id: GaTk
doi: 10.1016/j.cell.2019.01.007
external_id:
isi:
- '000457969200015'
pmid:
- '30712870'
intvolume: ' 176'
isi: 1
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.cell.2019.01.007
month: '02'
oa: 1
oa_version: Published Version
page: 844-855.e15
pmid: 1
project:
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: Cell
publication_status: published
publisher: Cell Press
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/cells-find-their-identity-using-a-mathematically-optimal-strategy/
scopus_import: '1'
status: public
title: Optimal decoding of cellular identities in a genetic network
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 176
year: '2019'
...
---
_id: '6049'
abstract:
- lang: eng
text: 'In this article it is shown that large systems with many interacting units
endowing multiple phases display self-oscillations in the presence of linear feedback
between the control and order parameters, where an Andronov–Hopf bifurcation takes
over the phase transition. This is simply illustrated through the mean field Landau
theory whose feedback dynamics turn out to be described by the Van der Pol equation
and it is then validated for the fully connected Ising model following heat bath
dynamics. Despite its simplicity, this theory accounts potentially for a rich
range of phenomena: here it is applied to describe in a stylized way (i) excess
demand-price cycles due to strong herding in a simple agent-based market model;
(ii) congestion waves in queuing networks triggered by user feedback to delays
in overloaded conditions; and (iii) metabolic network oscillations resulting from
cell growth control in a bistable phenotypic landscape.'
article_number: '045002'
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Daniele
full_name: De Martino, Daniele
id: 3FF5848A-F248-11E8-B48F-1D18A9856A87
last_name: De Martino
orcid: 0000-0002-5214-4706
citation:
ama: 'De Martino D. Feedback-induced self-oscillations in large interacting systems
subjected to phase transitions. Journal of Physics A: Mathematical and Theoretical.
2019;52(4). doi:10.1088/1751-8121/aaf2dd'
apa: 'De Martino, D. (2019). Feedback-induced self-oscillations in large interacting
systems subjected to phase transitions. Journal of Physics A: Mathematical
and Theoretical. IOP Publishing. https://doi.org/10.1088/1751-8121/aaf2dd'
chicago: 'De Martino, Daniele. “Feedback-Induced Self-Oscillations in Large Interacting
Systems Subjected to Phase Transitions.” Journal of Physics A: Mathematical
and Theoretical. IOP Publishing, 2019. https://doi.org/10.1088/1751-8121/aaf2dd.'
ieee: 'D. De Martino, “Feedback-induced self-oscillations in large interacting systems
subjected to phase transitions,” Journal of Physics A: Mathematical and Theoretical,
vol. 52, no. 4. IOP Publishing, 2019.'
ista: 'De Martino D. 2019. Feedback-induced self-oscillations in large interacting
systems subjected to phase transitions. Journal of Physics A: Mathematical and
Theoretical. 52(4), 045002.'
mla: 'De Martino, Daniele. “Feedback-Induced Self-Oscillations in Large Interacting
Systems Subjected to Phase Transitions.” Journal of Physics A: Mathematical
and Theoretical, vol. 52, no. 4, 045002, IOP Publishing, 2019, doi:10.1088/1751-8121/aaf2dd.'
short: 'D. De Martino, Journal of Physics A: Mathematical and Theoretical 52 (2019).'
date_created: 2019-02-24T22:59:19Z
date_published: 2019-01-07T00:00:00Z
date_updated: 2023-08-24T14:49:23Z
day: '07'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1088/1751-8121/aaf2dd
ec_funded: 1
external_id:
isi:
- '000455379500001'
file:
- access_level: open_access
checksum: 1112304ad363a6d8afaeccece36473cf
content_type: application/pdf
creator: kschuh
date_created: 2019-04-19T12:18:57Z
date_updated: 2020-07-14T12:47:17Z
file_id: '6344'
file_name: 2019_IOP_DeMartino.pdf
file_size: 1804557
relation: main_file
file_date_updated: 2020-07-14T12:47:17Z
has_accepted_license: '1'
intvolume: ' 52'
isi: 1
issue: '4'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: 'Journal of Physics A: Mathematical and Theoretical'
publication_status: published
publisher: IOP Publishing
quality_controlled: '1'
scopus_import: '1'
status: public
title: Feedback-induced self-oscillations in large interacting systems subjected to
phase transitions
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 52
year: '2019'
...
---
_id: '6046'
abstract:
- lang: eng
text: Sudden stress often triggers diverse, temporally structured gene expression
responses in microbes, but it is largely unknown how variable in time such responses
are and if genes respond in the same temporal order in every single cell. Here,
we quantified timing variability of individual promoters responding to sublethal
antibiotic stress using fluorescent reporters, microfluidics, and time‐lapse microscopy.
We identified lower and upper bounds that put definite constraints on timing variability,
which varies strongly among promoters and conditions. Timing variability can be
interpreted using results from statistical kinetics, which enable us to estimate
the number of rate‐limiting molecular steps underlying different responses. We
found that just a few critical steps control some responses while others rely
on dozens of steps. To probe connections between different stress responses, we
then tracked the temporal order and response time correlations of promoter pairs
in individual cells. Our results support that, when bacteria are exposed to the
antibiotic nitrofurantoin, the ensuing oxidative stress and SOS responses are
part of the same causal chain of molecular events. In contrast, under trimethoprim,
the acid stress response and the SOS response are part of different chains of
events running in parallel. Our approach reveals fundamental constraints on gene
expression timing and provides new insights into the molecular events that underlie
the timing of stress responses.
acknowledged_ssus:
- _id: Bio
article_number: e8470
article_processing_charge: No
author:
- first_name: Karin
full_name: Mitosch, Karin
id: 39B66846-F248-11E8-B48F-1D18A9856A87
last_name: Mitosch
- first_name: Georg
full_name: Rieckh, Georg
id: 34DA8BD6-F248-11E8-B48F-1D18A9856A87
last_name: Rieckh
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Mitosch K, Rieckh G, Bollenbach MT. Temporal order and precision of complex
stress responses in individual bacteria. Molecular systems biology. 2019;15(2).
doi:10.15252/msb.20188470
apa: Mitosch, K., Rieckh, G., & Bollenbach, M. T. (2019). Temporal order and
precision of complex stress responses in individual bacteria. Molecular Systems
Biology. Embo Press. https://doi.org/10.15252/msb.20188470
chicago: Mitosch, Karin, Georg Rieckh, and Mark Tobias Bollenbach. “Temporal Order
and Precision of Complex Stress Responses in Individual Bacteria.” Molecular
Systems Biology. Embo Press, 2019. https://doi.org/10.15252/msb.20188470.
ieee: K. Mitosch, G. Rieckh, and M. T. Bollenbach, “Temporal order and precision
of complex stress responses in individual bacteria,” Molecular systems biology,
vol. 15, no. 2. Embo Press, 2019.
ista: Mitosch K, Rieckh G, Bollenbach MT. 2019. Temporal order and precision of
complex stress responses in individual bacteria. Molecular systems biology. 15(2),
e8470.
mla: Mitosch, Karin, et al. “Temporal Order and Precision of Complex Stress Responses
in Individual Bacteria.” Molecular Systems Biology, vol. 15, no. 2, e8470,
Embo Press, 2019, doi:10.15252/msb.20188470.
short: K. Mitosch, G. Rieckh, M.T. Bollenbach, Molecular Systems Biology 15 (2019).
date_created: 2019-02-24T22:59:18Z
date_published: 2019-02-14T00:00:00Z
date_updated: 2023-08-24T14:49:53Z
day: '14'
department:
- _id: GaTk
doi: 10.15252/msb.20188470
external_id:
isi:
- '000459628300003'
pmid:
- '30765425'
intvolume: ' 15'
isi: 1
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pubmed/30765425
month: '02'
oa: 1
oa_version: Submitted Version
pmid: 1
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 25EB3A80-B435-11E9-9278-68D0E5697425
grant_number: RGP0042/2013
name: Revealing the fundamental limits of cell growth
publication: Molecular systems biology
publication_status: published
publisher: Embo Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Temporal order and precision of complex stress responses in individual bacteria
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 15
year: '2019'
...