---
_id: '12478'
abstract:
- lang: eng
text: In Gram negative bacteria, the multiple antibiotic resistance or mar operon,
is known to control the expression of multi-drug efflux genes that protect bacteria
from a wide range of drugs. As many different chemical compounds can induce this
operon, identifying the parameters that govern the dynamics of its induction is
crucial to better characterize the processes of tolerance and resistance. Most
experiments have assumed that the properties of the mar transcriptional network
can be inferred from population measurements. However, measurements from an asynchronous
population of cells can mask underlying phenotypic variations of single cells.
We monitored the activity of the mar promoter in single Escherichia coli cells
in linear micro-colonies and established that the response to a steady level of
inducer was most heterogeneous within individual colonies for an intermediate
value of inducer. Specifically, sub-lineages defined by contiguous daughter-cells
exhibited similar promoter activity, whereas activity was greatly variable between
different sub-lineages. Specific sub-trees of uniform promoter activity persisted
over several generations. Statistical analyses of the lineages suggest that the
presence of these sub-trees is the signature of an inducible memory of the promoter
state that is transmitted from mother to daughter cells. This single-cell study
reveals that the degree of epigenetic inheritance changes as a function of inducer
concentration, suggesting that phenotypic inheritance may be an inducible phenotype.
acknowledgement: This work was supported by NIH P50 award P50GM081892-02 to the University
of Chicago, a catalyst grant from the Chicago Biomedical Consortium with support
from The Searle Funds at The Chicago Community Trust to PC, and a Yen Fellowship
to CCG. MA was partially supported by PAPIIT-UNAM grant IN-11322.
article_number: '1049255'
article_processing_charge: Yes
article_type: original
author:
- 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: L
full_name: Bruneaux, L
last_name: Bruneaux
- first_name: P
full_name: Oikonomou, P
last_name: Oikonomou
- first_name: M
full_name: Aldana, M
last_name: Aldana
- first_name: P
full_name: Cluzel, P
last_name: Cluzel
citation:
ama: Guet CC, Bruneaux L, Oikonomou P, Aldana M, Cluzel P. Monitoring lineages of
growing and dividing bacteria reveals an inducible memory of mar operon
expression. Frontiers in Microbiology. 2023;14. doi:10.3389/fmicb.2023.1049255
apa: Guet, C. C., Bruneaux, L., Oikonomou, P., Aldana, M., & Cluzel, P. (2023).
Monitoring lineages of growing and dividing bacteria reveals an inducible memory
of mar operon expression. Frontiers in Microbiology. Frontiers.
https://doi.org/10.3389/fmicb.2023.1049255
chicago: Guet, Calin C, L Bruneaux, P Oikonomou, M Aldana, and P Cluzel. “Monitoring
Lineages of Growing and Dividing Bacteria Reveals an Inducible Memory of Mar
Operon Expression.” Frontiers in Microbiology. Frontiers, 2023. https://doi.org/10.3389/fmicb.2023.1049255.
ieee: C. C. Guet, L. Bruneaux, P. Oikonomou, M. Aldana, and P. Cluzel, “Monitoring
lineages of growing and dividing bacteria reveals an inducible memory of mar
operon expression,” Frontiers in Microbiology, vol. 14. Frontiers, 2023.
ista: Guet CC, Bruneaux L, Oikonomou P, Aldana M, Cluzel P. 2023. Monitoring lineages
of growing and dividing bacteria reveals an inducible memory of mar operon
expression. Frontiers in Microbiology. 14, 1049255.
mla: Guet, Calin C., et al. “Monitoring Lineages of Growing and Dividing Bacteria
Reveals an Inducible Memory of Mar Operon Expression.” Frontiers in
Microbiology, vol. 14, 1049255, Frontiers, 2023, doi:10.3389/fmicb.2023.1049255.
short: C.C. Guet, L. Bruneaux, P. Oikonomou, M. Aldana, P. Cluzel, Frontiers in
Microbiology 14 (2023).
date_created: 2023-02-02T08:13:28Z
date_published: 2023-06-20T00:00:00Z
date_updated: 2023-08-02T06:25:04Z
day: '20'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.3389/fmicb.2023.1049255
external_id:
isi:
- '001030002600001'
pmid:
- '37485524'
file:
- access_level: open_access
checksum: 7dd322347512afaa5daf72a0154f2f07
content_type: application/pdf
creator: dernst
date_created: 2023-07-31T07:16:34Z
date_updated: 2023-07-31T07:16:34Z
file_id: '13322'
file_name: 2023_FrontiersMicrobiology_Guet.pdf
file_size: 6452841
relation: main_file
success: 1
file_date_updated: 2023-07-31T07:16:34Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Microbiology
publication_identifier:
eissn:
- 1664-302X
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: Monitoring lineages of growing and dividing bacteria reveals an inducible memory
of mar operon expression
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: 14
year: '2023'
...
---
_id: '10939'
abstract:
- lang: eng
text: Understanding and characterising biochemical processes inside single cells
requires experimental platforms that allow one to perturb and observe the dynamics
of such processes as well as computational methods to build and parameterise models
from the collected data. Recent progress with experimental platforms and optogenetics
has made it possible to expose each cell in an experiment to an individualised
input and automatically record cellular responses over days with fine time resolution.
However, methods to infer parameters of stochastic kinetic models from single-cell
longitudinal data have generally been developed under the assumption that experimental
data is sparse and that responses of cells to at most a few different input perturbations
can be observed. Here, we investigate and compare different approaches for calculating
parameter likelihoods of single-cell longitudinal data based on approximations
of the chemical master equation (CME) with a particular focus on coupling the
linear noise approximation (LNA) or moment closure methods to a Kalman filter.
We show that, as long as cells are measured sufficiently frequently, coupling
the LNA to a Kalman filter allows one to accurately approximate likelihoods and
to infer model parameters from data even in cases where the LNA provides poor
approximations of the CME. Furthermore, the computational cost of filtering-based
iterative likelihood evaluation scales advantageously in the number of measurement
times and different input perturbations and is thus ideally suited for data obtained
from modern experimental platforms. To demonstrate the practical usefulness of
these results, we perform an experiment in which single cells, equipped with an
optogenetic gene expression system, are exposed to various different light-input
sequences and measured at several hundred time points and use parameter inference
based on iterative likelihood evaluation to parameterise a stochastic model of
the system.
acknowledgement: We thank Virgile Andreani for useful discussions about the model
and parameter inference. We thank Johan Paulsson and Jeffrey J Tabor for kind gifts
of plasmids. R was supported by the ANR grant CyberCircuits (ANR-18-CE91-0002).
The funders had no role in study design, data collection and analysis, decision
to publish, or preparation of the manuscript.
article_number: e1009950
article_processing_charge: No
article_type: original
author:
- first_name: Anđela
full_name: Davidović, Anđela
last_name: Davidović
- 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: Gregory
full_name: Batt, Gregory
last_name: Batt
- first_name: Jakob
full_name: Ruess, Jakob
id: 4A245D00-F248-11E8-B48F-1D18A9856A87
last_name: Ruess
orcid: 0000-0003-1615-3282
citation:
ama: Davidović A, Chait RP, Batt G, Ruess J. Parameter inference for stochastic
biochemical models from perturbation experiments parallelised at the single cell
level. PLoS Computational Biology. 2022;18(3). doi:10.1371/journal.pcbi.1009950
apa: Davidović, A., Chait, R. P., Batt, G., & Ruess, J. (2022). Parameter inference
for stochastic biochemical models from perturbation experiments parallelised at
the single cell level. PLoS Computational Biology. Public Library of Science.
https://doi.org/10.1371/journal.pcbi.1009950
chicago: Davidović, Anđela, Remy P Chait, Gregory Batt, and Jakob Ruess. “Parameter
Inference for Stochastic Biochemical Models from Perturbation Experiments Parallelised
at the Single Cell Level.” PLoS Computational Biology. Public Library of
Science, 2022. https://doi.org/10.1371/journal.pcbi.1009950.
ieee: A. Davidović, R. P. Chait, G. Batt, and J. Ruess, “Parameter inference for
stochastic biochemical models from perturbation experiments parallelised at the
single cell level,” PLoS Computational Biology, vol. 18, no. 3. Public
Library of Science, 2022.
ista: Davidović A, Chait RP, Batt G, Ruess J. 2022. Parameter inference for stochastic
biochemical models from perturbation experiments parallelised at the single cell
level. PLoS Computational Biology. 18(3), e1009950.
mla: Davidović, Anđela, et al. “Parameter Inference for Stochastic Biochemical Models
from Perturbation Experiments Parallelised at the Single Cell Level.” PLoS
Computational Biology, vol. 18, no. 3, e1009950, Public Library of Science,
2022, doi:10.1371/journal.pcbi.1009950.
short: A. Davidović, R.P. Chait, G. Batt, J. Ruess, PLoS Computational Biology 18
(2022).
date_created: 2022-04-03T22:01:42Z
date_published: 2022-03-18T00:00:00Z
date_updated: 2022-04-04T10:21:53Z
day: '18'
ddc:
- '570'
- '000'
department:
- _id: CaGu
doi: 10.1371/journal.pcbi.1009950
file:
- access_level: open_access
checksum: 458ef542761fb714ced214f240daf6b2
content_type: application/pdf
creator: dernst
date_created: 2022-04-04T10:14:39Z
date_updated: 2022-04-04T10:14:39Z
file_id: '10947'
file_name: 2022_PLoSCompBio_Davidovic.pdf
file_size: 2958642
relation: main_file
success: 1
file_date_updated: 2022-04-04T10:14:39Z
has_accepted_license: '1'
intvolume: ' 18'
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
publication: PLoS Computational Biology
publication_identifier:
eissn:
- 1553-7358
issn:
- 1553-734X
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://gitlab.pasteur.fr/adavidov/inferencelnakf
scopus_import: '1'
status: public
title: Parameter inference for stochastic biochemical models from perturbation experiments
parallelised at the single cell level
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 18
year: '2022'
...
---
_id: '11713'
abstract:
- lang: eng
text: "Objective: MazF is a sequence-specific endoribonuclease-toxin of the MazEF
toxin–antitoxin system. MazF cleaves single-stranded ribonucleic acid (RNA) regions
at adenine–cytosine–adenine (ACA) sequences in the bacterium Escherichia coli.
The MazEF system has been used in various biotechnology and synthetic biology
applications. In this study, we infer how ectopic mazF overexpression affects
production of heterologous proteins. To this end, we quantified the levels of
fluorescent proteins expressed in E. coli from reporters translated from the ACA-containing
or ACA-less messenger RNAs (mRNAs). Additionally, we addressed the impact of the
5′-untranslated region of these reporter mRNAs under the same conditions by comparing
expression from mRNAs that comprise (canonical mRNA) or lack this region (leaderless
mRNA).\r\nResults: Flow cytometry analysis indicates that during mazF overexpression,
fluorescent proteins are translated from the canonical as well as leaderless mRNAs.
Our analysis further indicates that longer mazF overexpression generally increases
the concentration of fluorescent proteins translated from ACA-less mRNAs, however
it also substantially increases bacterial population heterogeneity. Finally, our
results suggest that the strength and duration of mazF overexpression should be
optimized for each experimental setup, to maximize the heterologous protein production
and minimize the amount of phenotypic heterogeneity in bacterial populations,
which is unfavorable in biotechnological processes."
acknowledgement: "We acknowledge the Max Perutz Labs FACS Facility together with Thomas
Sauer. NN is grateful to Călin C. Guet for his support.\r\nThis work was funded
by the Elise Richter grant V738 of the Austrian Science Fund (FWF), and the FWF
Lise Meitner grant M1697, to NN; and by the FWF grant P22249, FWF Special Research
Program RNA-REG F43 (subproject F4316), and FWF doctoral program RNA Biology (W1207),
to IM. Open access funding provided by the Austrian Science Fund."
article_number: '173'
article_processing_charge: No
article_type: letter_note
author:
- first_name: Nela
full_name: Nikolic, Nela
id: 42D9CABC-F248-11E8-B48F-1D18A9856A87
last_name: Nikolic
orcid: 0000-0001-9068-6090
- first_name: Martina
full_name: Sauert, Martina
last_name: Sauert
- first_name: Tanino G.
full_name: Albanese, Tanino G.
last_name: Albanese
- first_name: Isabella
full_name: Moll, Isabella
last_name: Moll
citation:
ama: Nikolic N, Sauert M, Albanese TG, Moll I. Quantifying heterologous gene expression
during ectopic MazF production in Escherichia coli. BMC Research Notes.
2022;15. doi:10.1186/s13104-022-06061-9
apa: Nikolic, N., Sauert, M., Albanese, T. G., & Moll, I. (2022). Quantifying
heterologous gene expression during ectopic MazF production in Escherichia coli.
BMC Research Notes. Springer Nature. https://doi.org/10.1186/s13104-022-06061-9
chicago: Nikolic, Nela, Martina Sauert, Tanino G. Albanese, and Isabella Moll. “Quantifying
Heterologous Gene Expression during Ectopic MazF Production in Escherichia Coli.”
BMC Research Notes. Springer Nature, 2022. https://doi.org/10.1186/s13104-022-06061-9.
ieee: N. Nikolic, M. Sauert, T. G. Albanese, and I. Moll, “Quantifying heterologous
gene expression during ectopic MazF production in Escherichia coli,” BMC Research
Notes, vol. 15. Springer Nature, 2022.
ista: Nikolic N, Sauert M, Albanese TG, Moll I. 2022. Quantifying heterologous gene
expression during ectopic MazF production in Escherichia coli. BMC Research Notes.
15, 173.
mla: Nikolic, Nela, et al. “Quantifying Heterologous Gene Expression during Ectopic
MazF Production in Escherichia Coli.” BMC Research Notes, vol. 15, 173,
Springer Nature, 2022, doi:10.1186/s13104-022-06061-9.
short: N. Nikolic, M. Sauert, T.G. Albanese, I. Moll, BMC Research Notes 15 (2022).
date_created: 2022-08-01T09:04:27Z
date_published: 2022-05-13T00:00:00Z
date_updated: 2022-08-01T09:27:40Z
day: '13'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1186/s13104-022-06061-9
external_id:
pmid:
- '35562780'
file:
- access_level: open_access
checksum: 008156e5340e9789f0f6d82bde4d347a
content_type: application/pdf
creator: dernst
date_created: 2022-08-01T09:24:42Z
date_updated: 2022-08-01T09:24:42Z
file_id: '11714'
file_name: 2022_BMCResearchNotes_Nikolic.pdf
file_size: 1545310
relation: main_file
success: 1
file_date_updated: 2022-08-01T09:24:42Z
has_accepted_license: '1'
intvolume: ' 15'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 26956E74-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: V00738
name: Bacterial toxin-antitoxin systems as antiphage defense mechanisms
publication: BMC Research Notes
publication_identifier:
issn:
- 1756-0500
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1186/s13104-022-06152-7
scopus_import: '1'
status: public
title: Quantifying heterologous gene expression during ectopic MazF production in
Escherichia coli
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: 15
year: '2022'
...
---
_id: '10736'
abstract:
- lang: eng
text: Predicting function from sequence is a central problem of biology. Currently,
this is possible only locally in a narrow mutational neighborhood around a wildtype
sequence rather than globally from any sequence. Using random mutant libraries,
we developed a biophysical model that accounts for multiple features of σ70 binding
bacterial promoters to predict constitutive gene expression levels from any sequence.
We experimentally and theoretically estimated that 10–20% of random sequences
lead to expression and ~80% of non-expressing sequences are one mutation away
from a functional promoter. The potential for generating expression from random
sequences is so pervasive that selection acts against σ70-RNA polymerase binding
sites even within inter-genic, promoter-containing regions. This pervasiveness
of σ70-binding sites implies that emergence of promoters is not the limiting step
in gene regulatory evolution. Ultimately, the inclusion of novel features of promoter
function into a mechanistic model enabled not only more accurate predictions of
gene expression levels, but also identified that promoters evolve more rapidly
than previously thought.
acknowledgement: 'We thank Hande Acar, Nicholas H Barton, Rok Grah, Tiago Paixao,
Maros Pleska, Anna Staron, and Murat Tugrul for insightful comments and input on
the manuscript. This work was supported by: Sir Henry Dale Fellowship jointly funded
by the Wellcome Trust and the Royal Society (grant number 216779/Z/19/Z) to ML;
IPC Grant from IST Austria to ML and SS; European Research Council Funding Programme
7 (2007–2013, grant agreement number 648440) to JPB.'
article_number: e64543
article_processing_charge: No
article_type: original
author:
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Srdjan
full_name: Sarikas, Srdjan
id: 35F0286E-F248-11E8-B48F-1D18A9856A87
last_name: Sarikas
- first_name: Magdalena
full_name: Steinrueck, Magdalena
last_name: Steinrueck
- first_name: David
full_name: Toledo-Aparicio, David
last_name: Toledo-Aparicio
- 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: 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
citation:
ama: Lagator M, Sarikas S, Steinrueck M, et al. Predicting bacterial promoter function
and evolution from random sequences. eLife. 2022;11. doi:10.7554/eLife.64543
apa: Lagator, M., Sarikas, S., Steinrueck, M., Toledo-Aparicio, D., Bollback, J.
P., Guet, C. C., & Tkačik, G. (2022). Predicting bacterial promoter function
and evolution from random sequences. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.64543
chicago: Lagator, Mato, Srdjan Sarikas, Magdalena Steinrueck, David Toledo-Aparicio,
Jonathan P Bollback, Calin C Guet, and Gašper Tkačik. “Predicting Bacterial Promoter
Function and Evolution from Random Sequences.” ELife. eLife Sciences Publications,
2022. https://doi.org/10.7554/eLife.64543.
ieee: M. Lagator et al., “Predicting bacterial promoter function and evolution
from random sequences,” eLife, vol. 11. eLife Sciences Publications, 2022.
ista: Lagator M, Sarikas S, Steinrueck M, Toledo-Aparicio D, Bollback JP, Guet CC,
Tkačik G. 2022. Predicting bacterial promoter function and evolution from random
sequences. eLife. 11, e64543.
mla: Lagator, Mato, et al. “Predicting Bacterial Promoter Function and Evolution
from Random Sequences.” ELife, vol. 11, e64543, eLife Sciences Publications,
2022, doi:10.7554/eLife.64543.
short: M. Lagator, S. Sarikas, M. Steinrueck, D. Toledo-Aparicio, J.P. Bollback,
C.C. Guet, G. Tkačik, ELife 11 (2022).
date_created: 2022-02-06T23:01:32Z
date_published: 2022-01-26T00:00:00Z
date_updated: 2023-08-02T14:09:02Z
day: '26'
ddc:
- '576'
department:
- _id: CaGu
- _id: GaTk
- _id: NiBa
doi: 10.7554/eLife.64543
ec_funded: 1
external_id:
isi:
- '000751104400001'
pmid:
- '35080492'
file:
- access_level: open_access
checksum: decdcdf600ff51e9a9703b49ca114170
content_type: application/pdf
creator: cchlebak
date_created: 2022-02-07T07:14:09Z
date_updated: 2022-02-07T07:14:09Z
file_id: '10739'
file_name: 2022_ELife_Lagator.pdf
file_size: 5604343
relation: main_file
success: 1
file_date_updated: 2022-02-07T07:14:09Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2578D616-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Predicting bacterial promoter function and evolution from random sequences
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: '2022'
...
---
_id: '10812'
abstract:
- lang: eng
text: Several promising strategies based on combining or cycling different antibiotics
have been proposed to increase efficacy and counteract resistance evolution, but
we still lack a deep understanding of the physiological responses and genetic
mechanisms that underlie antibiotic interactions and the clinical applicability
of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological
stress responses and emerging resistance mutations (occurring at different time
scales) generate complex and often unpredictable dynamics. In this Review, we
present our current understanding of bacterial cell physiology and genetics of
responses to antibiotics. We emphasize recently discovered mechanisms of synergistic
and antagonistic drug interactions, hysteresis in temporal interactions between
antibiotics that arise from microbial physiology and interactions between antibiotics
and resistance mutations that can cause collateral sensitivity or cross-resistance.
We discuss possible connections between the different phenomena and indicate relevant
research directions. A better and more unified understanding of drug and genetic
interactions is likely to advance antibiotic therapy.
acknowledgement: The authors thank B. Kavčič and H. Schulenburg for constructive feedback
on the manuscript.
article_processing_charge: No
article_type: review
author:
- first_name: Roderich
full_name: Römhild, Roderich
id: 68E56E44-62B0-11EA-B963-444F3DDC885E
last_name: Römhild
orcid: 0000-0001-9480-5261
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
- first_name: Dan I.
full_name: Andersson, Dan I.
last_name: Andersson
citation:
ama: Römhild R, Bollenbach MT, Andersson DI. The physiology and genetics of bacterial
responses to antibiotic combinations. Nature Reviews Microbiology. 2022;20:478-490.
doi:10.1038/s41579-022-00700-5
apa: Römhild, R., Bollenbach, M. T., & Andersson, D. I. (2022). The physiology
and genetics of bacterial responses to antibiotic combinations. Nature Reviews
Microbiology. Springer Nature. https://doi.org/10.1038/s41579-022-00700-5
chicago: Römhild, Roderich, Mark Tobias Bollenbach, and Dan I. Andersson. “The Physiology
and Genetics of Bacterial Responses to Antibiotic Combinations.” Nature Reviews
Microbiology. Springer Nature, 2022. https://doi.org/10.1038/s41579-022-00700-5.
ieee: R. Römhild, M. T. Bollenbach, and D. I. Andersson, “The physiology and genetics
of bacterial responses to antibiotic combinations,” Nature Reviews Microbiology,
vol. 20. Springer Nature, pp. 478–490, 2022.
ista: Römhild R, Bollenbach MT, Andersson DI. 2022. The physiology and genetics
of bacterial responses to antibiotic combinations. Nature Reviews Microbiology.
20, 478–490.
mla: Römhild, Roderich, et al. “The Physiology and Genetics of Bacterial Responses
to Antibiotic Combinations.” Nature Reviews Microbiology, vol. 20, Springer
Nature, 2022, pp. 478–90, doi:10.1038/s41579-022-00700-5.
short: R. Römhild, M.T. Bollenbach, D.I. Andersson, Nature Reviews Microbiology
20 (2022) 478–490.
date_created: 2022-03-04T04:33:49Z
date_published: 2022-08-01T00:00:00Z
date_updated: 2023-08-02T14:41:44Z
day: '01'
department:
- _id: CaGu
doi: 10.1038/s41579-022-00700-5
external_id:
isi:
- '000763891900001'
pmid:
- '35241807'
intvolume: ' 20'
isi: 1
keyword:
- General Immunology and Microbiology
- Microbiology
- Infectious Diseases
language:
- iso: eng
month: '08'
oa_version: None
page: 478-490
pmid: 1
publication: Nature Reviews Microbiology
publication_identifier:
eissn:
- 1740-1534
issn:
- 1740-1526
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: The physiology and genetics of bacterial responses to antibiotic combinations
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 20
year: '2022'
...
---
_id: '11339'
abstract:
- lang: eng
text: The interaction between a cell and its environment shapes fundamental intracellular
processes such as cellular metabolism. In most cases growth rate is treated as
a proximal metric for understanding the cellular metabolic status. However, changes
in growth rate might not reflect metabolic variations in individuals responding
to environmental fluctuations. Here we use single-cell microfluidics-microscopy
combined with transcriptomics, proteomics and mathematical modelling to quantify
the accumulation of glucose within Escherichia coli cells. In contrast to the
current consensus, we reveal that environmental conditions which are comparatively
unfavourable for growth, where both nutrients and salinity are depleted, increase
glucose accumulation rates in individual bacteria and population subsets. We find
that these changes in metabolic function are underpinned by variations at the
translational and posttranslational level but not at the transcriptional level
and are not dictated by changes in cell size. The metabolic response-characteristics
identified greatly advance our fundamental understanding of the interactions between
bacteria and their environment and have important ramifications when investigating
cellular processes where salinity plays an important role.
acknowledgement: G.G. was supported by an EPSRC DTP PhD studentship (EP/M506527/1).
M.V. and K.T.A. gratefully acknowledge financial support from the EPSRC (EP/N014391/1).
U.L. was supported through a BBSRC grant (BB/V008021/1) and an MRC Proximity to
Discovery EXCITEME2 grant (MCPC17189). This work was further supported by a Royal
Society Research Grant (RG180007) awarded to S.P. and a QUEX Initiator grant awarded
to S.P. and K.T.A.. D.S.M., T.A.R. and S.P.’s work in this area is also supported
by a Marie Skłodowska-Curie project SINGEK (H2020-MSCA-ITN-2015-675752) and the
Gordon and Betty Moore Foundation Marine Microbiology Initiative (GBMF5514). B.M.I.
acknowledges support from a Wellcome Trust Institutional Strategic Support Award
to the University of Exeter (204909/Z/16/Z). This project utilised equipment funded
by the Wellcome Trust Institutional Strategic Support Fund (WT097835MF), Wellcome
Trust Multi User Equipment Award (WT101650MA) and BBSRC LOLA award (BB/K003240/1).
article_number: '385'
article_processing_charge: No
article_type: original
author:
- first_name: Georgina
full_name: Glover, Georgina
last_name: Glover
- first_name: Margaritis
full_name: Voliotis, Margaritis
last_name: Voliotis
- first_name: Urszula
full_name: Łapińska, Urszula
last_name: Łapińska
- first_name: Brandon M.
full_name: Invergo, Brandon M.
last_name: Invergo
- first_name: Darren
full_name: Soanes, Darren
last_name: Soanes
- first_name: Paul
full_name: O’Neill, Paul
last_name: O’Neill
- first_name: Karen
full_name: Moore, Karen
last_name: Moore
- first_name: Nela
full_name: Nikolic, Nela
id: 42D9CABC-F248-11E8-B48F-1D18A9856A87
last_name: Nikolic
orcid: 0000-0001-9068-6090
- first_name: Peter
full_name: Petrov, Peter
last_name: Petrov
- first_name: David S.
full_name: Milner, David S.
last_name: Milner
- first_name: Sumita
full_name: Roy, Sumita
last_name: Roy
- first_name: Kate
full_name: Heesom, Kate
last_name: Heesom
- first_name: Thomas A.
full_name: Richards, Thomas A.
last_name: Richards
- first_name: Krasimira
full_name: Tsaneva-Atanasova, Krasimira
last_name: Tsaneva-Atanasova
- first_name: Stefano
full_name: Pagliara, Stefano
last_name: Pagliara
citation:
ama: Glover G, Voliotis M, Łapińska U, et al. Nutrient and salt depletion synergistically
boosts glucose metabolism in individual Escherichia coli cells. Communications
Biology. 2022;5. doi:10.1038/s42003-022-03336-6
apa: Glover, G., Voliotis, M., Łapińska, U., Invergo, B. M., Soanes, D., O’Neill,
P., … Pagliara, S. (2022). Nutrient and salt depletion synergistically boosts
glucose metabolism in individual Escherichia coli cells. Communications Biology.
Springer Nature. https://doi.org/10.1038/s42003-022-03336-6
chicago: Glover, Georgina, Margaritis Voliotis, Urszula Łapińska, Brandon M. Invergo,
Darren Soanes, Paul O’Neill, Karen Moore, et al. “Nutrient and Salt Depletion
Synergistically Boosts Glucose Metabolism in Individual Escherichia Coli Cells.”
Communications Biology. Springer Nature, 2022. https://doi.org/10.1038/s42003-022-03336-6.
ieee: G. Glover et al., “Nutrient and salt depletion synergistically boosts
glucose metabolism in individual Escherichia coli cells,” Communications Biology,
vol. 5. Springer Nature, 2022.
ista: Glover G, Voliotis M, Łapińska U, Invergo BM, Soanes D, O’Neill P, Moore K,
Nikolic N, Petrov P, Milner DS, Roy S, Heesom K, Richards TA, Tsaneva-Atanasova
K, Pagliara S. 2022. Nutrient and salt depletion synergistically boosts glucose
metabolism in individual Escherichia coli cells. Communications Biology. 5, 385.
mla: Glover, Georgina, et al. “Nutrient and Salt Depletion Synergistically Boosts
Glucose Metabolism in Individual Escherichia Coli Cells.” Communications Biology,
vol. 5, 385, Springer Nature, 2022, doi:10.1038/s42003-022-03336-6.
short: G. Glover, M. Voliotis, U. Łapińska, B.M. Invergo, D. Soanes, P. O’Neill,
K. Moore, N. Nikolic, P. Petrov, D.S. Milner, S. Roy, K. Heesom, T.A. Richards,
K. Tsaneva-Atanasova, S. Pagliara, Communications Biology 5 (2022).
date_created: 2022-05-01T22:01:41Z
date_published: 2022-04-20T00:00:00Z
date_updated: 2023-08-03T06:45:26Z
day: '20'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1038/s42003-022-03336-6
external_id:
isi:
- '000784143400001'
pmid:
- '35444215'
file:
- access_level: open_access
checksum: 7c6f76ab17393d650825cc240edc84b3
content_type: application/pdf
creator: dernst
date_created: 2022-05-02T06:26:26Z
date_updated: 2022-05-02T06:26:26Z
file_id: '11342'
file_name: 2022_CommBiology_Glover.pdf
file_size: 2827723
relation: main_file
success: 1
file_date_updated: 2022-05-02T06:26:26Z
has_accepted_license: '1'
intvolume: ' 5'
isi: 1
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: Communications Biology
publication_identifier:
eissn:
- 2399-3642
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nutrient and salt depletion synergistically boosts glucose metabolism in individual
Escherichia coli cells
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: 5
year: '2022'
...
---
_id: '11843'
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 mouse dendritic cells (DCs) as a 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 the pathogenic strain CFT073 to CD14 reduced DC migration
by overactivation of integrins and blunted expression of co-stimulatory molecules
by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both
rate-limiting factors of T cell activation. This response was binary at the single-cell
level, but averaged in larger populations exposed to both piliated and non-piliated
pathogens, presumably via the exchange of immunomodulatory cytokines. 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 strains CFT073, UTI89,
and 536, Frank Assen, Vlad Gavra, 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 IG, the European Research Council (CoG 724373),
and the Austrian Science Fund (FWF P29911) to MS.
article_number: e78995
article_processing_charge: Yes
article_type: original
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
- 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: 0000-0002-6620-9179
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.
eLife. 2022;11. doi:10.7554/eLife.78995
apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &
Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the
host immune response by binding to CD14. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.78995
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.” ELife. eLife Sciences
Publications, 2022. https://doi.org/10.7554/eLife.78995.
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,” eLife, vol. 11. eLife Sciences Publications,
2022.
ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type
1 piliated uropathogenic Escherichia coli hijack the host immune response by binding
to CD14. eLife. 11, e78995.
mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack
the Host Immune Response by Binding to CD14.” ELife, vol. 11, e78995, eLife
Sciences Publications, 2022, doi:10.7554/eLife.78995.
short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt,
ELife 11 (2022).
date_created: 2022-08-14T22:01:46Z
date_published: 2022-07-26T00:00:00Z
date_updated: 2023-08-03T12:54:21Z
day: '26'
ddc:
- '570'
department:
- _id: MiSi
- _id: CaGu
doi: 10.7554/eLife.78995
ec_funded: 1
external_id:
isi:
- '000838410200001'
file:
- access_level: open_access
checksum: 002a3c7c7ea5caa9af9cfbea308f6ea4
content_type: application/pdf
creator: cchlebak
date_created: 2022-08-16T08:57:37Z
date_updated: 2022-08-16T08:57:37Z
file_id: '11861'
file_name: 2022_eLife_Tomasek.pdf
file_size: 2057577
relation: main_file
success: 1
file_date_updated: 2022-08-16T08:57:37Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
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: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
record:
- id: '10316'
relation: earlier_version
status: public
scopus_import: '1'
status: public
title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response
by binding to CD14
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: '2022'
...
---
_id: '12333'
abstract:
- lang: eng
text: Together, copy-number and point mutations form the basis for most evolutionary
novelty, through the process of gene duplication and divergence. While a plethora
of genomic data reveals the long-term fate of diverging coding sequences and their
cis-regulatory elements, little is known about the early dynamics around the duplication
event itself. In microorganisms, selection for increased gene expression often
drives the expansion of gene copy-number mutations, which serves as a crude adaptation,
prior to divergence through refining point mutations. Using a simple synthetic
genetic reporter system that can distinguish between copy-number and point mutations,
we study their early and transient adaptive dynamics in real time in Escherichia
coli. We find two qualitatively different routes of adaptation, depending on the
level of functional improvement needed. In conditions of high gene expression
demand, the two mutation types occur as a combination. However, under low gene
expression demand, copy-number and point mutations are mutually exclusive; here,
owing to their higher frequency, adaptation is dominated by copy-number mutations,
in a process we term amplification hindrance. Ultimately, due to high reversal
rates and pleiotropic cost, copy-number mutations may not only serve as a crude
and transient adaptation, but also constrain sequence divergence over evolutionary
time scales.
acknowledgement: "We are grateful to N Barton, F Kondrashov, M Lagator, M Pleska,
R Roemhild, D Siekhaus, and G\r\nTkacik for input on the manuscript and to K Tomasek
for help with flow cytometry."
article_number: e82240
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: 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, Guet CC. Adaptation dynamics between copynumber and point mutations.
eLife. 2022;11. doi:10.7554/ELIFE.82240
apa: Tomanek, I., & Guet, C. C. (2022). Adaptation dynamics between copynumber
and point mutations. ELife. eLife Sciences Publications. https://doi.org/10.7554/ELIFE.82240
chicago: Tomanek, Isabella, and Calin C Guet. “Adaptation Dynamics between Copynumber
and Point Mutations.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/ELIFE.82240.
ieee: I. Tomanek and C. C. Guet, “Adaptation dynamics between copynumber and point
mutations,” eLife, vol. 11. eLife Sciences Publications, 2022.
ista: Tomanek I, Guet CC. 2022. Adaptation dynamics between copynumber and point
mutations. eLife. 11, e82240.
mla: Tomanek, Isabella, and Calin C. Guet. “Adaptation Dynamics between Copynumber
and Point Mutations.” ELife, vol. 11, e82240, eLife Sciences Publications,
2022, doi:10.7554/ELIFE.82240.
short: I. Tomanek, C.C. Guet, ELife 11 (2022).
date_created: 2023-01-22T23:00:55Z
date_published: 2022-12-22T00:00:00Z
date_updated: 2023-08-03T14:23:07Z
day: '22'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.7554/ELIFE.82240
external_id:
isi:
- '000912674700001'
file:
- access_level: open_access
checksum: 9321fd5f06ff59d5e2d33daee84b3da1
content_type: application/pdf
creator: dernst
date_created: 2023-01-23T08:56:21Z
date_updated: 2023-01-23T08:56:21Z
file_id: '12338'
file_name: 2022_eLife_Tomanek.pdf
file_size: 8835954
relation: main_file
success: 1
file_date_updated: 2023-01-23T08:56:21Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://doi.org/10.5281/zenodo.6974122
record:
- id: '12339'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Adaptation dynamics between copynumber and point mutations
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: '2022'
...
---
_id: '12339'
abstract:
- lang: eng
text: 'Copy-number and point mutations form the basis for most evolutionary novelty
through the process of gene duplication and divergence. While a plethora of genomic
sequence data reveals the long-term fate of diverging coding sequences and their
cis-regulatory elements, little is known about the early dynamics around the duplication
event itself. In microorganisms, selection for increased gene expression often
drives the expansion of gene copy-number mutations, which serves as a crude adaptation,
prior to divergence through refining point mutations. Using a simple synthetic
genetic system that allows us to distinguish copy-number and point mutations,
we study their early and transient adaptive dynamics in real-time in Escherichia
coli. We find two qualitatively different routes of adaptation depending on the
level of functional improvement selected for: In conditions of high gene expression
demand, the two types of mutations occur as a combination. Under low gene expression
demand, negative epistasis between the two types of mutations renders them mutually
exclusive. Thus, owing to their higher frequency, adaptation is dominated by copy-number
mutations. Ultimately, due to high rates of reversal and pleiotropic cost, copy-number
mutations may not only serve as a crude and transient adaptation but also constrain
sequence divergence over evolutionary time scales.'
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
- 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, Guet CC. Flow cytometry YFP and CFP data and deep sequencing data
of populations evolving in galactose. 2022. doi:10.5061/dryad.rfj6q57ds
apa: Tomanek, I., & Guet, C. C. (2022). Flow cytometry YFP and CFP data and
deep sequencing data of populations evolving in galactose. Dryad. https://doi.org/10.5061/dryad.rfj6q57ds
chicago: Tomanek, Isabella, and Calin C Guet. “Flow Cytometry YFP and CFP Data and
Deep Sequencing Data of Populations Evolving in Galactose.” Dryad, 2022. https://doi.org/10.5061/dryad.rfj6q57ds.
ieee: I. Tomanek and C. C. Guet, “Flow cytometry YFP and CFP data and deep sequencing
data of populations evolving in galactose.” Dryad, 2022.
ista: Tomanek I, Guet CC. 2022. Flow cytometry YFP and CFP data and deep sequencing
data of populations evolving in galactose, Dryad, 10.5061/dryad.rfj6q57ds.
mla: Tomanek, Isabella, and Calin C. Guet. Flow Cytometry YFP and CFP Data and
Deep Sequencing Data of Populations Evolving in Galactose. Dryad, 2022, doi:10.5061/dryad.rfj6q57ds.
short: I. Tomanek, C.C. Guet, (2022).
date_created: 2023-01-23T09:00:37Z
date_published: 2022-12-23T00:00:00Z
date_updated: 2023-08-03T14:23:06Z
day: '23'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.5061/dryad.rfj6q57ds
main_file_link:
- open_access: '1'
url: https://doi.org/10.5061/dryad.rfj6q57ds
month: '12'
oa: 1
oa_version: Published Version
publisher: Dryad
related_material:
record:
- id: '12333'
relation: used_in_publication
status: public
status: public
title: Flow cytometry YFP and CFP data and deep sequencing data of populations evolving
in galactose
type: research_data_reference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_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: 2023-08-07T13:36:55Z
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:
- '15537374'
issn:
- '15537366'
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 17
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.
date_created: 2021-07-11T22:01:18Z
date_published: 2021-06-04T00:00:00Z
date_updated: 2023-08-10T14:11:19Z
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: The Wittgenstein Prize
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: '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.
date_created: 2021-08-08T22:01:28Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2023-08-10T14:22:48Z
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:
- '19448252'
issn:
- '19448244'
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
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: 2023-08-11T10:26:29Z
day: '28'
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
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: 2023-08-14T13:01:38Z
day: '01'
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 34
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).
date_created: 2021-03-23T10:11:46Z
date_published: 2021-03-08T00:00:00Z
date_updated: 2024-02-21T12:41:57Z
day: '08'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.7554/elife.65993
ec_funded: 1
external_id:
isi:
- '000631050900001'
file:
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file_size: 1390469
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file_date_updated: 2021-03-23T10:12:58Z
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intvolume: ' 10'
isi: 1
keyword:
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language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
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: 'CyberCircuits: 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:
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relation: research_data
status: public
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2021'
...
---
_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.
date_created: 2021-11-18T15:05:06Z
date_published: 2021-11-18T00:00:00Z
date_updated: 2023-09-07T13:34:38Z
day: '18'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MiSi
- _id: CaGu
- _id: GradSch
doi: 10.15479/at:ista:10307
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date_created: 2021-11-18T15:07:31Z
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creator: ktomasek
date_created: 2021-11-18T15:07:46Z
date_updated: 2022-12-20T23:30:05Z
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file_id: '10309'
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file_date_updated: 2022-12-20T23:30:05Z
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language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: '73'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '10316'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
title: Pathogenic Escherichia coli hijack the host immune response
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2021'
...
---
_id: '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.).
date_created: 2021-11-19T12:24:16Z
date_published: 2021-10-18T00:00:00Z
date_updated: 2024-03-28T23:30:35Z
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: submitted
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: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2021'
...
---
_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
- 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: 2021-01-12T08:17:17Z
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
intvolume: ' 2173'
language:
- iso: eng
month: '07'
oa_version: None
page: 233-246
publication: Photoswitching Proteins
publication_identifier:
eisbn:
- '9781071607558'
eissn:
- '19406029'
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 2173
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:
- access_level: open_access
content_type: application/pdf
creator: rgrah
date_created: 2020-07-27T12:00:07Z
date_updated: 2020-07-27T12:00:07Z
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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: 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
day: '25'
ddc:
- '000'
- '570'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642
external_id:
isi:
- '000526725200019'
file:
- access_level: open_access
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
relation: main_file
file_date_updated: 2020-07-14T12:48:00Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
issue: '2'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
publication: PLOS Computational Biology
publication_identifier:
issn:
- 1553-7358
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
record:
- id: '9716'
relation: research_data
status: deleted
- id: '9776'
relation: research_data
status: public
- id: '9779'
relation: used_in_publication
status: public
- id: '8155'
relation: dissertation_contains
status: public
- id: '9777'
relation: research_data
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 16
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
date_created: 2020-12-20T10:00:26Z
date_published: 2020-12-21T00:00:00Z
date_updated: 2024-02-21T12:41:57Z
day: '21'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:8951
file:
- access_level: open_access
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
success: 1
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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
file_id: '8954'
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
date_created: 2020-01-28T10:41:49Z
date_published: 2020-01-28T00:00:00Z
date_updated: 2024-02-21T12:42:31Z
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
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.
date_created: 2020-04-24T16:00:51Z
date_published: 2020-04-24T00:00:00Z
date_updated: 2023-09-22T09:20:10Z
day: '24'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:7680
file:
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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
embargo_to: open_access
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
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: 2024-03-28T23:30:37Z
day: '01'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.1038/s41559-020-1132-7
external_id:
isi:
- '000519008300005'
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creator: dernst
date_created: 2020-10-09T09:56:01Z
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file_name: 2020_NatureEcolEvo_Tomanek.pdf
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file_date_updated: 2020-10-09T09:56:01Z
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isi: 1
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language:
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month: '04'
oa: 1
oa_version: Submitted Version
page: 612-625
project:
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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:
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relation: dissertation_contains
status: public
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relation: research_data
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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: '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.
date_created: 2020-10-13T13:02:33Z
date_published: 2020-10-13T00:00:00Z
date_updated: 2023-09-07T13:22:42Z
day: '13'
ddc:
- '576'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:8653
file:
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checksum: c01d9f59794b4b70528f37637c17ad02
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date_created: 2020-10-16T12:14:21Z
date_updated: 2021-10-20T22:30:03Z
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file_size: 15405675
relation: main_file
file_date_updated: 2021-10-20T22:30:03Z
has_accepted_license: '1'
keyword:
- duplication
- amplification
- promoter
- CNV
- AMGET
- experimental evolution
- Escherichia coli
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '117'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7652'
relation: research_data
status: public
status: public
supervisor:
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
title: The evolution of gene expression by copy number and point mutations
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '6465'
abstract:
- lang: eng
text: Tight control over protein degradation is a fundamental requirement for cells
to respond rapidly to various stimuli and adapt to a fluctuating environment.
Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons)
for the precise regulation of protein expression profiles in mammalian cells by
modulating target protein half-lives in a predictable manner. Using the well-established
tetracycline gene-regulation system as a model, we show that the dynamics of protein
expression can be tuned by fusing appropriate degron tags to gene regulators.
Next, we apply this degron library to tune a synthetic pulse-generating circuit
in mammalian cells. With this toolbox we establish a set of pulse generators with
tailored pulse lengths and magnitudes of protein expression. This methodology
will prove useful in the functional roles of essential proteins, fine-tuning of
gene-expression systems, and enabling a higher complexity in the design of synthetic
biological systems in mammalian cells.
article_number: '2013'
article_processing_charge: No
author:
- first_name: Hélène
full_name: Chassin, Hélène
last_name: Chassin
- first_name: Marius
full_name: Müller, Marius
last_name: Müller
- first_name: Marcel
full_name: Tigges, Marcel
last_name: Tigges
- first_name: Leo
full_name: Scheller, Leo
last_name: Scheller
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Martin
full_name: Fussenegger, Martin
last_name: Fussenegger
citation:
ama: Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. A modular
degron library for synthetic circuits in mammalian cells. Nature Communications.
2019;10(1). doi:10.1038/s41467-019-09974-5
apa: Chassin, H., Müller, M., Tigges, M., Scheller, L., Lang, M., & Fussenegger,
M. (2019). A modular degron library for synthetic circuits in mammalian cells.
Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-09974-5
chicago: Chassin, Hélène, Marius Müller, Marcel Tigges, Leo Scheller, Moritz Lang,
and Martin Fussenegger. “A Modular Degron Library for Synthetic Circuits in Mammalian
Cells.” Nature Communications. Springer Nature, 2019. https://doi.org/10.1038/s41467-019-09974-5.
ieee: H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, and M. Fussenegger,
“A modular degron library for synthetic circuits in mammalian cells,” Nature
Communications, vol. 10, no. 1. Springer Nature, 2019.
ista: Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. 2019. A
modular degron library for synthetic circuits in mammalian cells. Nature Communications.
10(1), 2013.
mla: Chassin, Hélène, et al. “A Modular Degron Library for Synthetic Circuits in
Mammalian Cells.” Nature Communications, vol. 10, no. 1, 2013, Springer
Nature, 2019, doi:10.1038/s41467-019-09974-5.
short: H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, M. Fussenegger, Nature
Communications 10 (2019).
date_created: 2019-05-19T21:59:14Z
date_published: 2019-05-01T00:00:00Z
date_updated: 2023-08-25T10:33:51Z
day: '01'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1038/s41467-019-09974-5
external_id:
isi:
- '000466338600006'
file:
- access_level: open_access
checksum: e214d3e4f8c81e35981583c4569b51b8
content_type: application/pdf
creator: dernst
date_created: 2019-05-20T07:33:54Z
date_updated: 2020-07-14T12:47:31Z
file_id: '6471'
file_name: 2019_NatureComm_Chassin.pdf
file_size: 1191827
relation: main_file
file_date_updated: 2020-07-14T12:47:31Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
issue: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_identifier:
eissn:
- '20411723'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1038/s41467-023-36111-0
scopus_import: '1'
status: public
title: A modular degron library for synthetic circuits in mammalian cells
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: 10
year: '2019'
...
---
_id: '6717'
abstract:
- lang: eng
text: With the recent publication by Silpe and Bassler (2019), considering phage
detection of a bacterial quorum-sensing (QS) autoinducer, we now have as many
as five examples of phage-associated intercellular communication (Table 1). Each
potentially involves ecological inferences by phages as to concentrations of surrounding
phage-infected or uninfected bacteria. While the utility of phage detection of
bacterial QS molecules may at first glance appear to be straightforward, we suggest
in this commentary that the underlying ecological explanation is unlikely to be
simple.
article_number: '1171'
article_processing_charge: Yes (via OA deal)
author:
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
- first_name: Stephen T.
full_name: Abedon, Stephen T.
last_name: Abedon
citation:
ama: 'Igler C, Abedon ST. Commentary: A host-produced quorum-sensing autoinducer
controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 2019;10.
doi:10.3389/fmicb.2019.01171'
apa: 'Igler, C., & Abedon, S. T. (2019). Commentary: A host-produced quorum-sensing
autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology.
Frontiers. https://doi.org/10.3389/fmicb.2019.01171'
chicago: 'Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing
Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology.
Frontiers, 2019. https://doi.org/10.3389/fmicb.2019.01171.'
ieee: 'C. Igler and S. T. Abedon, “Commentary: A host-produced quorum-sensing autoinducer
controls a phage lysis-lysogeny decision,” Frontiers in Microbiology, vol.
10. Frontiers, 2019.'
ista: 'Igler C, Abedon ST. 2019. Commentary: A host-produced quorum-sensing autoinducer
controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 10, 1171.'
mla: 'Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing
Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology,
vol. 10, 1171, Frontiers, 2019, doi:10.3389/fmicb.2019.01171.'
short: C. Igler, S.T. Abedon, Frontiers in Microbiology 10 (2019).
date_created: 2019-07-28T21:59:18Z
date_published: 2019-06-03T00:00:00Z
date_updated: 2023-08-29T06:41:20Z
day: '03'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.3389/fmicb.2019.01171
external_id:
isi:
- '000470131200001'
file:
- access_level: open_access
checksum: 317a06067e9a8e717bb55f23e0d77ba7
content_type: application/pdf
creator: apreinsp
date_created: 2019-07-29T07:51:54Z
date_updated: 2020-07-14T12:47:38Z
file_id: '6722'
file_name: 2019_Frontiers_Igler.pdf
file_size: 246151
relation: main_file
file_date_updated: 2020-07-14T12:47:38Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
project:
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
grant_number: '24573'
name: Design principles underlying genetic switch architecture (DOC Fellowship)
publication: Frontiers in Microbiology
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny
decision'
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: 10
year: '2019'
...
---
_id: '6784'
abstract:
- lang: eng
text: Mathematical models have been used successfully at diverse scales of biological
organization, ranging from ecology and population dynamics to stochastic reaction
events occurring between individual molecules in single cells. Generally, many
biological processes unfold across multiple scales, with mutations being the best
studied example of how stochasticity at the molecular scale can influence outcomes
at the population scale. In many other contexts, however, an analogous link between
micro- and macro-scale remains elusive, primarily due to the challenges involved
in setting up and analyzing multi-scale models. Here, we employ such a model to
investigate how stochasticity propagates from individual biochemical reaction
events in the bacterial innate immune system to the ecology of bacteria and bacterial
viruses. We show analytically how the dynamics of bacterial populations are shaped
by the activities of immunity-conferring enzymes in single cells and how the ecological
consequences imply optimal bacterial defense strategies against viruses. Our results
suggest that bacterial populations in the presence of viruses can either optimize
their initial growth rate or their population size, with the first strategy favoring
simple immunity featuring a single restriction modification system and the second
strategy favoring complex bacterial innate immunity featuring several simultaneously
active restriction modification systems.
article_number: e1007168
article_processing_charge: No
article_type: original
author:
- first_name: Jakob
full_name: Ruess, Jakob
id: 4A245D00-F248-11E8-B48F-1D18A9856A87
last_name: Ruess
orcid: 0000-0003-1615-3282
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- 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
citation:
ama: Ruess J, Pleska M, Guet CC, Tkačik G. Molecular noise of innate immunity shapes
bacteria-phage ecologies. PLoS Computational Biology. 2019;15(7). doi:10.1371/journal.pcbi.1007168
apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Molecular noise
of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology.
Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168
chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Molecular
Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational
Biology. Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.
ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Molecular noise of innate
immunity shapes bacteria-phage ecologies,” PLoS Computational Biology,
vol. 15, no. 7. Public Library of Science, 2019.
ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Molecular noise of innate immunity
shapes bacteria-phage ecologies. PLoS Computational Biology. 15(7), e1007168.
mla: Ruess, Jakob, et al. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage
Ecologies.” PLoS Computational Biology, vol. 15, no. 7, e1007168, Public
Library of Science, 2019, doi:10.1371/journal.pcbi.1007168.
short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15
(2019).
date_created: 2019-08-11T21:59:19Z
date_published: 2019-07-02T00:00:00Z
date_updated: 2023-08-29T07:10:06Z
day: '02'
ddc:
- '570'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007168
external_id:
isi:
- '000481577700032'
file:
- access_level: open_access
checksum: 7ded4721b41c2a0fc66a1c634540416a
content_type: application/pdf
creator: dernst
date_created: 2019-08-12T12:27:26Z
date_updated: 2020-07-14T12:47:40Z
file_id: '6803'
file_name: 2019_PlosComputBiology_Ruess.pdf
file_size: 2200003
relation: main_file
file_date_updated: 2020-07-14T12:47:40Z
has_accepted_license: '1'
intvolume: ' 15'
isi: 1
issue: '7'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 251D65D8-B435-11E9-9278-68D0E5697425
grant_number: '24210'
name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems
at the Single-Cell Level
- _id: 251BCBEC-B435-11E9-9278-68D0E5697425
grant_number: RGY0079/2011
name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification
Systems
publication: PLoS Computational Biology
publication_identifier:
eissn:
- 1553-7358
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
record:
- id: '9786'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Molecular noise of innate immunity shapes bacteria-phage ecologies
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: 15
year: '2019'
...
---
_id: '9786'
article_processing_charge: No
author:
- first_name: Jakob
full_name: Ruess, Jakob
id: 4A245D00-F248-11E8-B48F-1D18A9856A87
last_name: Ruess
orcid: 0000-0003-1615-3282
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- 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
citation:
ama: Ruess J, Pleska M, Guet CC, Tkačik G. Supporting text and results. 2019. doi:10.1371/journal.pcbi.1007168.s001
apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Supporting text
and results. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168.s001
chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Supporting
Text and Results.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.s001.
ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Supporting text and results.”
Public Library of Science, 2019.
ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Supporting text and results, Public
Library of Science, 10.1371/journal.pcbi.1007168.s001.
mla: Ruess, Jakob, et al. Supporting Text and Results. Public Library of
Science, 2019, doi:10.1371/journal.pcbi.1007168.s001.
short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019).
date_created: 2021-08-06T08:23:43Z
date_published: 2019-07-02T00:00:00Z
date_updated: 2023-08-29T07:10:05Z
day: '02'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007168.s001
month: '07'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '6784'
relation: used_in_publication
status: public
status: public
title: Supporting text and results
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2019'
...
---
_id: '7147'
abstract:
- lang: eng
text: "The expression of a gene is characterised by its transcription factors and
the function processing them. If the transcription factors are not affected by
gene products, the regulating function is often represented as a combinational
logic circuit, where the outputs (product) are determined by current input values
(transcription factors) only, and are hence independent on their relative arrival
times. However, the simultaneous arrival of transcription factors (TFs) in genetic
circuits is a strong assumption, given that the processes of transcription and
translation of a gene into a protein introduce intrinsic time delays and that
there is no global synchronisation among the arrival times of different molecular
species at molecular targets.\r\n\r\nIn this paper, we construct an experimentally
implementable genetic circuit with two inputs and a single output, such that,
in presence of small delays in input arrival, the circuit exhibits qualitatively
distinct observable phenotypes. In particular, these phenotypes are long lived
transients: they all converge to a single value, but so slowly, that they seem
stable for an extended time period, longer than typical experiment duration. We
used rule-based language to prototype our circuit, and we implemented a search
for finding the parameter combinations raising the phenotypes of interest.\r\n\r\nThe
behaviour of our prototype circuit has wide implications. First, it suggests that
GRNs can exploit event timing to create phenotypes. Second, it opens the possibility
that GRNs are using event timing to react to stimuli and memorise events, without
explicit feedback in regulation. From the modelling perspective, our prototype
circuit demonstrates the critical importance of analysing the transient dynamics
at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions."
alternative_title:
- LNCS
article_processing_charge: No
author:
- 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: Thomas A
full_name: Henzinger, Thomas A
id: 40876CD8-F248-11E8-B48F-1D18A9856A87
last_name: Henzinger
orcid: 0000−0002−2985−7724
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
- first_name: Tatjana
full_name: Petrov, Tatjana
id: 3D5811FC-F248-11E8-B48F-1D18A9856A87
last_name: Petrov
orcid: 0000-0002-9041-0905
- first_name: Ali
full_name: Sezgin, Ali
id: 4C7638DA-F248-11E8-B48F-1D18A9856A87
last_name: Sezgin
citation:
ama: 'Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. Transient memory in gene
regulation. In: 17th International Conference on Computational Methods in Systems
Biology. Vol 11773. Springer Nature; 2019:155-187. doi:10.1007/978-3-030-31304-3_9'
apa: 'Guet, C. C., Henzinger, T. A., Igler, C., Petrov, T., & Sezgin, A. (2019).
Transient memory in gene regulation. In 17th International Conference on Computational
Methods in Systems Biology (Vol. 11773, pp. 155–187). Trieste, Italy: Springer
Nature. https://doi.org/10.1007/978-3-030-31304-3_9'
chicago: Guet, Calin C, Thomas A Henzinger, Claudia Igler, Tatjana Petrov, and Ali
Sezgin. “Transient Memory in Gene Regulation.” In 17th International Conference
on Computational Methods in Systems Biology, 11773:155–87. Springer Nature,
2019. https://doi.org/10.1007/978-3-030-31304-3_9.
ieee: C. C. Guet, T. A. Henzinger, C. Igler, T. Petrov, and A. Sezgin, “Transient
memory in gene regulation,” in 17th International Conference on Computational
Methods in Systems Biology, Trieste, Italy, 2019, vol. 11773, pp. 155–187.
ista: 'Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. 2019. Transient memory
in gene regulation. 17th International Conference on Computational Methods in
Systems Biology. CMSB: Computational Methods in Systems Biology, LNCS, vol. 11773,
155–187.'
mla: Guet, Calin C., et al. “Transient Memory in Gene Regulation.” 17th International
Conference on Computational Methods in Systems Biology, vol. 11773, Springer
Nature, 2019, pp. 155–87, doi:10.1007/978-3-030-31304-3_9.
short: C.C. Guet, T.A. Henzinger, C. Igler, T. Petrov, A. Sezgin, in:, 17th International
Conference on Computational Methods in Systems Biology, Springer Nature, 2019,
pp. 155–187.
conference:
end_date: 2019-09-20
location: Trieste, Italy
name: 'CMSB: Computational Methods in Systems Biology'
start_date: 2019-09-18
date_created: 2019-12-04T16:07:50Z
date_published: 2019-09-17T00:00:00Z
date_updated: 2023-09-06T11:18:08Z
day: '17'
department:
- _id: CaGu
- _id: ToHe
doi: 10.1007/978-3-030-31304-3_9
external_id:
isi:
- '000557875100009'
intvolume: ' 11773'
isi: 1
language:
- iso: eng
month: '09'
oa_version: None
page: 155-187
project:
- _id: 25F42A32-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z211
name: The Wittgenstein Prize
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
grant_number: '24573'
name: Design principles underlying genetic switch architecture
publication: 17th International Conference on Computational Methods in Systems Biology
publication_identifier:
eissn:
- 1611-3349
isbn:
- '9783030313036'
- '9783030313043'
issn:
- 0302-9743
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Transient memory in gene regulation
type: conference
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 11773
year: '2019'
...
---
_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: 2023-09-08T13:23:42Z
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
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. 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. 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. 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, 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. 116(8), 2821–2830.
mla: Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.”
Proceedings of the National Academy of Sciences, 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 116
(2019) 2821–2830.
date_created: 2018-12-11T11:45:08Z
date_published: 2019-02-19T00:00:00Z
date_updated: 2023-09-11T14:09:34Z
day: '19'
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
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 116
year: '2019'
...
---
_id: '7016'
abstract:
- lang: eng
text: Organisms cope with change by employing transcriptional regulators. However,
when faced with rare environments, the evolution of transcriptional regulators
and their promoters may be too slow. We ask whether the intrinsic instability
of gene duplication and amplification provides a generic alternative to canonical
gene regulation. By real-time monitoring of gene copy number mutations in E. coli,
we show that gene duplications and amplifications enable adaptation to fluctuating
environments by rapidly generating copy number, and hence expression level, polymorphism.
This ‘amplification-mediated gene expression tuning’ occurs on timescales similar
to canonical gene regulation and can deal with rapid environmental changes. Mathematical
modeling shows that amplifications also tune gene expression in stochastic environments
where transcription factor-based schemes are hard to evolve or maintain. The fleeting
nature of gene amplifications gives rise to a generic population-level mechanism
that relies on genetic heterogeneity to rapidly tune expression of any gene, without
leaving any genomic signature.
article_processing_charge: No
author:
- first_name: Isabella
full_name: Tomanek, Isabella
id: 3981F020-F248-11E8-B48F-1D18A9856A87
last_name: Tomanek
orcid: 0000-0001-6197-363X
citation:
ama: Tomanek I. Data for the paper “Gene amplification as a form of population-level
gene expression regulation.” 2019. doi:10.15479/AT:ISTA:7016
apa: Tomanek, I. (2019). Data for the paper “Gene amplification as a form of population-level
gene expression regulation.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7016
chicago: Tomanek, Isabella. “Data for the Paper ‘Gene Amplification as a Form of
Population-Level Gene Expression Regulation.’” Institute of Science and Technology
Austria, 2019. https://doi.org/10.15479/AT:ISTA:7016.
ieee: I. Tomanek, “Data for the paper ‘Gene amplification as a form of population-level
gene expression regulation.’” Institute of Science and Technology Austria, 2019.
ista: Tomanek I. 2019. Data for the paper ‘Gene amplification as a form of population-level
gene expression regulation’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:7016.
mla: Tomanek, Isabella. Data for the Paper “Gene Amplification as a Form of Population-Level
Gene Expression Regulation.” Institute of Science and Technology Austria,
2019, doi:10.15479/AT:ISTA:7016.
short: I. Tomanek, (2019).
contributor:
- contributor_type: project_leader
first_name: Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
date_created: 2019-11-13T09:07:31Z
date_published: 2019-11-13T00:00:00Z
date_updated: 2024-02-21T12:45:25Z
day: '13'
ddc:
- '576'
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:7016
file:
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content_type: application/octet-stream
creator: itomanek
date_created: 2019-11-13T08:52:21Z
date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 1 - amplified.
file_id: '7017'
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file_size: 2456192500
relation: main_file
title: Locus1_amplified
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content_type: application/octet-stream
creator: itomanek
date_created: 2019-11-13T08:52:59Z
date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 1 - ancestral.
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creator: itomanek
date_created: 2019-11-13T08:54:10Z
date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 1 - amplified, after
DOG-selection.
file_id: '7019'
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file_size: 2878017264
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creator: itomanek
date_created: 2019-11-13T08:54:27Z
date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 2 - amplified.
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creator: itomanek
date_created: 2019-11-13T08:55:58Z
date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 2 - ancestral.
file_id: '7021'
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date_updated: 2020-07-14T12:47:47Z
description: Illumina whole genome sequence data for Locus 2 - amplified, after
DOG-selection.
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content_type: application/zip
creator: itomanek
date_created: 2020-01-14T11:22:27Z
date_updated: 2020-07-14T12:47:47Z
description: Compressed genbank file format containing the sequence of the chromosomal
reporter gene cassette.
file_id: '7273'
file_name: galK_dual_reporter_cassette.gb.zip
file_size: 4179
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title: DNA sequence of the chromosomal reporter gene cassette
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date_created: 2020-01-22T15:44:16Z
date_updated: 2020-07-14T12:47:47Z
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- access_level: open_access
checksum: 69c5dc5ca5c069a138183c934acc1778
content_type: application/zip
creator: itomanek
date_created: 2020-01-22T15:44:17Z
date_updated: 2020-07-14T12:47:47Z
description: microfluidics time trace data - see read_me_microfluidics
file_id: '7354'
file_name: microfuidics_data.zip
file_size: 8141727
relation: main_file
title: microfluidics data
file_date_updated: 2020-07-14T12:47:47Z
has_accepted_license: '1'
keyword:
- Escherichia coli
- gene amplification
- galactose
- DOG
- experimental evolution
- Illumina sequence data
- FACS data
- microfluidics data
month: '11'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7652'
relation: used_in_publication
status: public
status: public
title: Data for the paper "Gene amplification as a form of population-level gene expression
regulation"
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2019'
...
---
_id: '6371'
abstract:
- lang: eng
text: "Decades of studies have revealed the mechanisms of gene regulation in molecular
detail. We make use of such well-described regulatory systems to explore how the
molecular mechanisms of protein-protein and protein-DNA interactions shape the
dynamics and evolution of gene regulation. \r\n\r\ni) We uncover how the biophysics
of protein-DNA binding determines the potential of regulatory networks to evolve
and adapt, which can be captured using a simple mathematical model. \r\nii) The
evolution of regulatory connections can lead to a significant amount of crosstalk
between binding proteins. We explore the effect of crosstalk on gene expression
from a target promoter, which seems to be modulated through binding competition
at non-specific DNA sites. \r\niii) We investigate how the very same biophysical
characteristics as in i) can generate significant fitness costs for cells through
global crosstalk, meaning non-specific DNA binding across the genomic background.
\r\niv) Binding competition between proteins at a target promoter is a prevailing
regulatory feature due to the prevalence of co-regulation at bacterial promoters.
However, the dynamics of these systems are not always straightforward to determine
even if the molecular mechanisms of regulation are known. A detailed model of
the biophysical interactions reveals that interference between the regulatory
proteins can constitute a new, generic form of system memory that records the
history of the input signals at the promoter. \r\n\r\nWe demonstrate how the biophysics
of protein-DNA binding can be harnessed to investigate the principles that shape
and ultimately limit cellular gene regulation. These results provide a basis for
studies of higher-level functionality, which arises from the underlying regulation.
\ \r\n"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
citation:
ama: Igler C. On the nature of gene regulatory design - The biophysics of transcription
factor binding shapes gene regulation. 2019. doi:10.15479/AT:ISTA:6371
apa: Igler, C. (2019). On the nature of gene regulatory design - The biophysics
of transcription factor binding shapes gene regulation. Institute of Science
and Technology Austria. https://doi.org/10.15479/AT:ISTA:6371
chicago: Igler, Claudia. “On the Nature of Gene Regulatory Design - The Biophysics
of Transcription Factor Binding Shapes Gene Regulation.” Institute of Science
and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6371.
ieee: C. Igler, “On the nature of gene regulatory design - The biophysics of transcription
factor binding shapes gene regulation,” Institute of Science and Technology Austria,
2019.
ista: Igler C. 2019. On the nature of gene regulatory design - The biophysics of
transcription factor binding shapes gene regulation. Institute of Science and
Technology Austria.
mla: Igler, Claudia. On the Nature of Gene Regulatory Design - The Biophysics
of Transcription Factor Binding Shapes Gene Regulation. Institute of Science
and Technology Austria, 2019, doi:10.15479/AT:ISTA:6371.
short: C. Igler, On the Nature of Gene Regulatory Design - The Biophysics of Transcription
Factor Binding Shapes Gene Regulation, Institute of Science and Technology Austria,
2019.
date_created: 2019-05-03T11:55:51Z
date_published: 2019-05-03T00:00:00Z
date_updated: 2024-02-21T13:45:52Z
day: '03'
ddc:
- '576'
- '579'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:6371
file:
- access_level: open_access
checksum: c0085d47c58c9cbcab1b0a783480f6da
content_type: application/pdf
creator: cigler
date_created: 2019-05-03T11:54:52Z
date_updated: 2021-02-11T11:17:13Z
embargo: 2020-05-02
file_id: '6373'
file_name: IglerClaudia_OntheNatureofGeneRegulatoryDesign.pdf
file_size: 12597663
relation: main_file
- access_level: closed
checksum: 2eac954de1c8bbf7e6fb35ed0221ae8c
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: cigler
date_created: 2019-05-03T11:54:54Z
date_updated: 2020-07-14T12:47:28Z
embargo_to: open_access
file_id: '6374'
file_name: IglerClaudia_OntheNatureofGeneRegulatoryDesign.docx
file_size: 34644426
relation: source_file
file_date_updated: 2021-02-11T11:17:13Z
has_accepted_license: '1'
keyword:
- gene regulation
- biophysics
- transcription factor binding
- bacteria
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '152'
project:
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
grant_number: '24573'
name: Design principles underlying genetic switch architecture (DOC Fellowship)
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '67'
relation: part_of_dissertation
status: public
- id: '5585'
relation: popular_science
status: public
status: public
supervisor:
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
title: On the nature of gene regulatory design - The biophysics of transcription factor
binding shapes gene regulation
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...
---
_id: '305'
abstract:
- lang: eng
text: The hanging-drop network (HDN) is a technology platform based on a completely
open microfluidic network at the bottom of an inverted, surface-patterned substrate.
The platform is predominantly used for the formation, culturing, and interaction
of self-assembled spherical microtissues (spheroids) under precisely controlled
flow conditions. Here, we describe design, fabrication, and operation of microfluidic
hanging-drop networks.
acknowledgement: This work was financially supported by FP7 of the EU through the
project “Body on a chip,” ICT-FET-296257, and the ERC Advanced Grant “NeuroCMOS”
(contract 267351), as well as by an individual Ambizione Grant 142440 from the Swiss
National Science Foundation for Olivier Frey. The research leading to these results
also received funding from the People Programme (Marie Curie Actions) of the European
Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no.
[291734]. We would like to thank Alexander Stettler, ETH Zurich for his expertise
and support in the cleanroom, and we acknowledge the Single Cell Unit of D-BSSE,
ETH Zurich for assistance in microscopy issues. M.L. is grateful to the members
of the Guet and Tkačik groups, IST Austria, for valuable comments and support.
alternative_title:
- MIMB
author:
- first_name: Patrick
full_name: Misun, Patrick
last_name: Misun
- first_name: Axel
full_name: Birchler, Axel
last_name: Birchler
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Andreas
full_name: Hierlemann, Andreas
last_name: Hierlemann
- first_name: Olivier
full_name: Frey, Olivier
last_name: Frey
citation:
ama: Misun P, Birchler A, Lang M, Hierlemann A, Frey O. Fabrication and operation
of microfluidic hanging drop networks. Methods in Molecular Biology. 2018;1771:183-202.
doi:10.1007/978-1-4939-7792-5_15
apa: Misun, P., Birchler, A., Lang, M., Hierlemann, A., & Frey, O. (2018). Fabrication
and operation of microfluidic hanging drop networks. Methods in Molecular Biology.
Springer. https://doi.org/10.1007/978-1-4939-7792-5_15
chicago: Misun, Patrick, Axel Birchler, Moritz Lang, Andreas Hierlemann, and Olivier
Frey. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods
in Molecular Biology. Springer, 2018. https://doi.org/10.1007/978-1-4939-7792-5_15.
ieee: P. Misun, A. Birchler, M. Lang, A. Hierlemann, and O. Frey, “Fabrication and
operation of microfluidic hanging drop networks,” Methods in Molecular Biology,
vol. 1771. Springer, pp. 183–202, 2018.
ista: Misun P, Birchler A, Lang M, Hierlemann A, Frey O. 2018. Fabrication and operation
of microfluidic hanging drop networks. Methods in Molecular Biology. 1771, 183–202.
mla: Misun, Patrick, et al. “Fabrication and Operation of Microfluidic Hanging Drop
Networks.” Methods in Molecular Biology, vol. 1771, Springer, 2018, pp.
183–202, doi:10.1007/978-1-4939-7792-5_15.
short: P. Misun, A. Birchler, M. Lang, A. Hierlemann, O. Frey, Methods in Molecular
Biology 1771 (2018) 183–202.
date_created: 2018-12-11T11:45:43Z
date_published: 2018-01-01T00:00:00Z
date_updated: 2021-01-12T07:40:42Z
day: '01'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1007/978-1-4939-7792-5_15
ec_funded: 1
intvolume: ' 1771'
language:
- iso: eng
month: '01'
oa_version: None
page: 183 - 202
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Methods in Molecular Biology
publication_status: published
publisher: Springer
publist_id: '7574'
quality_controlled: '1'
scopus_import: 1
status: public
title: Fabrication and operation of microfluidic hanging drop networks
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1771
year: '2018'
...
---
_id: '723'
abstract:
- lang: eng
text: Escaping local optima is one of the major obstacles to function optimisation.
Using the metaphor of a fitness landscape, local optima correspond to hills separated
by fitness valleys that have to be overcome. We define a class of fitness valleys
of tunable difficulty by considering their length, representing the Hamming path
between the two optima and their depth, the drop in fitness. For this function
class we present a runtime comparison between stochastic search algorithms using
different search strategies. The (1+1) EA is a simple and well-studied evolutionary
algorithm that has to jump across the valley to a point of higher fitness because
it does not accept worsening moves (elitism). In contrast, the Metropolis algorithm
and the Strong Selection Weak Mutation (SSWM) algorithm, a famous process in population
genetics, are both able to cross the fitness valley by accepting worsening moves.
We show that the runtime of the (1+1) EA depends critically on the length of the
valley while the runtimes of the non-elitist algorithms depend crucially on the
depth of the valley. Moreover, we show that both SSWM and Metropolis can also
efficiently optimise a rugged function consisting of consecutive valleys.
article_processing_charge: No
author:
- first_name: Pietro
full_name: Oliveto, Pietro
last_name: Oliveto
- first_name: Tiago
full_name: Paixao, Tiago
id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
last_name: Paixao
orcid: 0000-0003-2361-3953
- first_name: Jorge
full_name: Pérez Heredia, Jorge
last_name: Pérez Heredia
- first_name: Dirk
full_name: Sudholt, Dirk
last_name: Sudholt
- first_name: Barbora
full_name: Trubenova, Barbora
id: 42302D54-F248-11E8-B48F-1D18A9856A87
last_name: Trubenova
orcid: 0000-0002-6873-2967
citation:
ama: Oliveto P, Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. How to escape
local optima in black box optimisation when non elitism outperforms elitism. Algorithmica.
2018;80(5):1604-1633. doi:10.1007/s00453-017-0369-2
apa: Oliveto, P., Paixao, T., Pérez Heredia, J., Sudholt, D., & Trubenova, B.
(2018). How to escape local optima in black box optimisation when non elitism
outperforms elitism. Algorithmica. Springer. https://doi.org/10.1007/s00453-017-0369-2
chicago: Oliveto, Pietro, Tiago Paixao, Jorge Pérez Heredia, Dirk Sudholt, and Barbora
Trubenova. “How to Escape Local Optima in Black Box Optimisation When Non Elitism
Outperforms Elitism.” Algorithmica. Springer, 2018. https://doi.org/10.1007/s00453-017-0369-2.
ieee: P. Oliveto, T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “How
to escape local optima in black box optimisation when non elitism outperforms
elitism,” Algorithmica, vol. 80, no. 5. Springer, pp. 1604–1633, 2018.
ista: Oliveto P, Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. 2018. How to
escape local optima in black box optimisation when non elitism outperforms elitism.
Algorithmica. 80(5), 1604–1633.
mla: Oliveto, Pietro, et al. “How to Escape Local Optima in Black Box Optimisation
When Non Elitism Outperforms Elitism.” Algorithmica, vol. 80, no. 5, Springer,
2018, pp. 1604–33, doi:10.1007/s00453-017-0369-2.
short: P. Oliveto, T. Paixao, J. Pérez Heredia, D. Sudholt, B. Trubenova, Algorithmica
80 (2018) 1604–1633.
date_created: 2018-12-11T11:48:09Z
date_published: 2018-05-01T00:00:00Z
date_updated: 2023-09-11T14:11:35Z
day: '01'
ddc:
- '576'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1007/s00453-017-0369-2
ec_funded: 1
external_id:
isi:
- '000428239300010'
file:
- access_level: open_access
checksum: 7d92f5d7be81e387edeec4f06442791c
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:08:14Z
date_updated: 2020-07-14T12:47:54Z
file_id: '4674'
file_name: IST-2018-1014-v1+1_2018_Paixao_Escape.pdf
file_size: 691245
relation: main_file
file_date_updated: 2020-07-14T12:47:54Z
has_accepted_license: '1'
intvolume: ' 80'
isi: 1
issue: '5'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: 1604 - 1633
project:
- _id: 25B1EC9E-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618091'
name: Speed of Adaptation in Population Genetics and Evolutionary Computation
publication: Algorithmica
publication_status: published
publisher: Springer
publist_id: '6957'
pubrep_id: '1014'
quality_controlled: '1'
scopus_import: '1'
status: public
title: How to escape local optima in black box optimisation when non elitism outperforms
elitism
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: 80
year: '2018'
...
---
_id: '503'
abstract:
- lang: eng
text: Buffers are essential for diluting bacterial cultures for flow cytometry analysis
in order to study bacterial physiology and gene expression parameters based on
fluorescence signals. Using a variety of constitutively expressed fluorescent
proteins in Escherichia coli K-12 strain MG1655, we found strong artifactual changes
in fluorescence levels after dilution into the commonly used flow cytometry buffer
phosphate-buffered saline (PBS) and two other buffer solutions, Tris-HCl and M9
salts. These changes appeared very rapidly after dilution, and were linked to
increased membrane permeability and loss in cell viability. We observed buffer-related
effects in several different E. coli strains, K-12, C and W, but not E. coli B,
which can be partially explained by differences in lipopolysaccharide (LPS) and
outer membrane composition. Supplementing the buffers with divalent cations responsible
for outer membrane stability, Mg2+ and Ca2+, preserved fluorescence signals, membrane
integrity and viability of E. coli. Thus, stabilizing the bacterial outer membrane
is essential for precise and unbiased measurements of fluorescence parameters
using flow cytometry.
acknowledged_ssus:
- _id: Bio
acknowledgement: "We thank R Chait and M Lagator for sharing Bacillus subtilis CR_Y1
and pZS*_2R-cIPtet-Venus-Prm, respectively. We are grateful to T Pilizota and all
members of the Guet lab for critically reading the manuscript. We also thank the
Bioimaging facility at IST Austria for assistance using the FACSAria III system.\r\n\r\n"
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: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- 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: Tomasek K, Bergmiller T, Guet CC. Lack of cations in flow cytometry buffers
affect fluorescence signals by reducing membrane stability and viability of Escherichia
coli strains. Journal of Biotechnology. 2018;268:40-52. doi:10.1016/j.jbiotec.2018.01.008
apa: Tomasek, K., Bergmiller, T., & Guet, C. C. (2018). Lack of cations in flow
cytometry buffers affect fluorescence signals by reducing membrane stability and
viability of Escherichia coli strains. Journal of Biotechnology. Elsevier.
https://doi.org/10.1016/j.jbiotec.2018.01.008
chicago: Tomasek, Kathrin, Tobias Bergmiller, and Calin C Guet. “Lack of Cations
in Flow Cytometry Buffers Affect Fluorescence Signals by Reducing Membrane Stability
and Viability of Escherichia Coli Strains.” Journal of Biotechnology. Elsevier,
2018. https://doi.org/10.1016/j.jbiotec.2018.01.008.
ieee: K. Tomasek, T. Bergmiller, and C. C. Guet, “Lack of cations in flow cytometry
buffers affect fluorescence signals by reducing membrane stability and viability
of Escherichia coli strains,” Journal of Biotechnology, vol. 268. Elsevier,
pp. 40–52, 2018.
ista: Tomasek K, Bergmiller T, Guet CC. 2018. Lack of cations in flow cytometry
buffers affect fluorescence signals by reducing membrane stability and viability
of Escherichia coli strains. Journal of Biotechnology. 268, 40–52.
mla: Tomasek, Kathrin, et al. “Lack of Cations in Flow Cytometry Buffers Affect
Fluorescence Signals by Reducing Membrane Stability and Viability of Escherichia
Coli Strains.” Journal of Biotechnology, vol. 268, Elsevier, 2018, pp.
40–52, doi:10.1016/j.jbiotec.2018.01.008.
short: K. Tomasek, T. Bergmiller, C.C. Guet, Journal of Biotechnology 268 (2018)
40–52.
date_created: 2018-12-11T11:46:50Z
date_published: 2018-02-20T00:00:00Z
date_updated: 2023-09-13T08:24:51Z
day: '20'
department:
- _id: CaGu
doi: 10.1016/j.jbiotec.2018.01.008
external_id:
isi:
- '000425715100006'
intvolume: ' 268'
isi: 1
language:
- iso: eng
month: '02'
oa_version: None
page: 40 - 52
publication: Journal of Biotechnology
publication_status: published
publisher: Elsevier
publist_id: '7317'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Lack of cations in flow cytometry buffers affect fluorescence signals by reducing
membrane stability and viability of Escherichia coli strains
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 268
year: '2018'
...
---
_id: '82'
abstract:
- lang: eng
text: In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage,
bacterial cells resistant to the phage commonly emerge and become the dominant
population of bacteria. Following the ascent of resistant mutants, the densities
of bacteria in these simple communities become limited by resources rather than
the phage. Despite the evolution of resistant hosts, upon which the phage cannot
replicate, the lytic phage population is most commonly maintained in an apparently
stable state with the resistant bacteria. Several mechanisms have been put forward
to account for this result. Here we report the results of population dynamic/evolution
experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli
in serial transfer cultures. We show that, following the ascent of λVIR-resistant
bacteria, λVIRis maintained in the majority of cases in maltose-limited minimal
media and in all cases in nutrient-rich broth. Using mathematical models and experiments,
we show that the dominant mechanism responsible for maintenance of λVIRin these
resource-limited populations dominated by resistant E. coli is a high rate of
either phenotypic or genetic transition from resistance to susceptibility—a hitherto
undemonstrated mechanism we term "leaky resistance." We discuss the
implications of leaky resistance to our understanding of the conditions for the
maintenance of phage in populations of bacteria—their “existence conditions.”.
article_number: '2005971'
article_processing_charge: Yes
author:
- first_name: Waqas
full_name: Chaudhry, Waqas
last_name: Chaudhry
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Nilang
full_name: Shah, Nilang
last_name: Shah
- first_name: Howard
full_name: Weiss, Howard
last_name: Weiss
- first_name: Ingrid
full_name: Mccall, Ingrid
last_name: Mccall
- first_name: Justin
full_name: Meyer, Justin
last_name: Meyer
- first_name: Animesh
full_name: Gupta, Animesh
last_name: Gupta
- 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: Bruce
full_name: Levin, Bruce
last_name: Levin
citation:
ama: Chaudhry W, Pleska M, Shah N, et al. Leaky resistance and the conditions for
the existence of lytic bacteriophage. PLoS Biology. 2018;16(8). doi:10.1371/journal.pbio.2005971
apa: Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin,
B. (2018). Leaky resistance and the conditions for the existence of lytic bacteriophage.
PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.2005971
chicago: Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall,
Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Leaky Resistance
and the Conditions for the Existence of Lytic Bacteriophage.” PLoS Biology.
Public Library of Science, 2018. https://doi.org/10.1371/journal.pbio.2005971.
ieee: W. Chaudhry et al., “Leaky resistance and the conditions for the existence
of lytic bacteriophage,” PLoS Biology, vol. 16, no. 8. Public Library of
Science, 2018.
ista: Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC,
Levin B. 2018. Leaky resistance and the conditions for the existence of lytic
bacteriophage. PLoS Biology. 16(8), 2005971.
mla: Chaudhry, Waqas, et al. “Leaky Resistance and the Conditions for the Existence
of Lytic Bacteriophage.” PLoS Biology, vol. 16, no. 8, 2005971, Public
Library of Science, 2018, doi:10.1371/journal.pbio.2005971.
short: W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta,
C.C. Guet, B. Levin, PLoS Biology 16 (2018).
date_created: 2018-12-11T11:44:32Z
date_published: 2018-08-16T00:00:00Z
date_updated: 2023-09-13T08:45:41Z
day: '16'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1371/journal.pbio.2005971
external_id:
isi:
- '000443383300024'
file:
- access_level: open_access
checksum: 527076f78265cd4ea192cd1569851587
content_type: application/pdf
creator: dernst
date_created: 2018-12-17T12:55:31Z
date_updated: 2020-07-14T12:48:10Z
file_id: '5706'
file_name: 2018_Plos_Chaudhry.pdf
file_size: 4007095
relation: main_file
file_date_updated: 2020-07-14T12:48:10Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
issue: '8'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
publication: PLoS Biology
publication_status: published
publisher: Public Library of Science
publist_id: '7972'
quality_controlled: '1'
related_material:
record:
- id: '9810'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Leaky resistance and the conditions for the existence of lytic bacteriophage
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: 16
year: '2018'
...
---
_id: '9810'
article_processing_charge: No
author:
- first_name: Waqas
full_name: Chaudhry, Waqas
last_name: Chaudhry
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Nilang
full_name: Shah, Nilang
last_name: Shah
- first_name: Howard
full_name: Weiss, Howard
last_name: Weiss
- first_name: Ingrid
full_name: Mccall, Ingrid
last_name: Mccall
- first_name: Justin
full_name: Meyer, Justin
last_name: Meyer
- first_name: Animesh
full_name: Gupta, Animesh
last_name: Gupta
- 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: Bruce
full_name: Levin, Bruce
last_name: Levin
citation:
ama: Chaudhry W, Pleska M, Shah N, et al. Numerical data used in figures. 2018.
doi:10.1371/journal.pbio.2005971.s008
apa: Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin,
B. (2018). Numerical data used in figures. Public Library of Science. https://doi.org/10.1371/journal.pbio.2005971.s008
chicago: Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall,
Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Numerical Data Used
in Figures.” Public Library of Science, 2018. https://doi.org/10.1371/journal.pbio.2005971.s008.
ieee: W. Chaudhry et al., “Numerical data used in figures.” Public Library
of Science, 2018.
ista: Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC,
Levin B. 2018. Numerical data used in figures, Public Library of Science, 10.1371/journal.pbio.2005971.s008.
mla: Chaudhry, Waqas, et al. Numerical Data Used in Figures. Public Library
of Science, 2018, doi:10.1371/journal.pbio.2005971.s008.
short: W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta,
C.C. Guet, B. Levin, (2018).
date_created: 2021-08-06T12:43:44Z
date_published: 2018-08-16T00:00:00Z
date_updated: 2023-09-13T08:45:41Z
day: '16'
department:
- _id: CaGu
doi: 10.1371/journal.pbio.2005971.s008
month: '08'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '82'
relation: used_in_publication
status: public
status: public
title: Numerical data used in figures
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2018'
...
---
_id: '457'
abstract:
- lang: eng
text: Temperate bacteriophages integrate in bacterial genomes as prophages and represent
an important source of genetic variation for bacterial evolution, frequently transmitting
fitness-augmenting genes such as toxins responsible for virulence of major pathogens.
However, only a fraction of bacteriophage infections are lysogenic and lead to
prophage acquisition, whereas the majority are lytic and kill the infected bacteria.
Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity
to bacteriophages are expected to act as a double-edged sword and increase the
odds of survival at the cost of depriving bacteria of potentially beneficial prophages.
We show that although restriction-modification systems as mechanisms of innate
immunity prevent both lytic and lysogenic infections indiscriminately in individual
bacteria, they increase the number of prophage-acquiring individuals at the population
level. We find that this counterintuitive result is a consequence of phage-host
population dynamics, in which restriction-modification systems delay infection
onset until bacteria reach densities at which the probability of lysogeny increases.
These results underscore the importance of population-level dynamics as a key
factor modulating costs and benefits of immunity to temperate bacteriophages
article_processing_charge: No
author:
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Dominik
full_name: Refardt, Dominik
last_name: Refardt
- first_name: Bruce
full_name: Levin, Bruce
last_name: Levin
- 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: Pleska M, Lang M, Refardt D, Levin B, Guet CC. Phage-host population dynamics
promotes prophage acquisition in bacteria with innate immunity. Nature Ecology
and Evolution. 2018;2(2):359-366. doi:10.1038/s41559-017-0424-z
apa: Pleska, M., Lang, M., Refardt, D., Levin, B., & Guet, C. C. (2018). Phage-host
population dynamics promotes prophage acquisition in bacteria with innate immunity.
Nature Ecology and Evolution. Springer Nature. https://doi.org/10.1038/s41559-017-0424-z
chicago: Pleska, Maros, Moritz Lang, Dominik Refardt, Bruce Levin, and Calin C Guet.
“Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with
Innate Immunity.” Nature Ecology and Evolution. Springer Nature, 2018.
https://doi.org/10.1038/s41559-017-0424-z.
ieee: M. Pleska, M. Lang, D. Refardt, B. Levin, and C. C. Guet, “Phage-host population
dynamics promotes prophage acquisition in bacteria with innate immunity,” Nature
Ecology and Evolution, vol. 2, no. 2. Springer Nature, pp. 359–366, 2018.
ista: Pleska M, Lang M, Refardt D, Levin B, Guet CC. 2018. Phage-host population
dynamics promotes prophage acquisition in bacteria with innate immunity. Nature
Ecology and Evolution. 2(2), 359–366.
mla: Pleska, Maros, et al. “Phage-Host Population Dynamics Promotes Prophage Acquisition
in Bacteria with Innate Immunity.” Nature Ecology and Evolution, vol. 2,
no. 2, Springer Nature, 2018, pp. 359–66, doi:10.1038/s41559-017-0424-z.
short: M. Pleska, M. Lang, D. Refardt, B. Levin, C.C. Guet, Nature Ecology and Evolution
2 (2018) 359–366.
date_created: 2018-12-11T11:46:35Z
date_published: 2018-02-01T00:00:00Z
date_updated: 2023-09-15T12:04:57Z
day: '01'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1038/s41559-017-0424-z
ec_funded: 1
external_id:
isi:
- '000426516400027'
intvolume: ' 2'
isi: 1
issue: '2'
language:
- iso: eng
month: '02'
oa_version: None
page: 359 - 366
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 251BCBEC-B435-11E9-9278-68D0E5697425
grant_number: RGY0079/2011
name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification
Systems (HFSP Young investigators' grant)
- _id: 251D65D8-B435-11E9-9278-68D0E5697425
grant_number: '24210'
name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems
at the Single-Cell Level (DOC Fellowship)
publication: Nature Ecology and Evolution
publication_status: published
publisher: Springer Nature
publist_id: '7364'
quality_controlled: '1'
related_material:
record:
- id: '202'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Phage-host population dynamics promotes prophage acquisition in bacteria with
innate immunity
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 2
year: '2018'
...
---
_id: '5984'
abstract:
- lang: eng
text: G-protein-coupled receptors (GPCRs) form the largest receptor family, relay
environmental stimuli to changes in cell behavior and represent prime drug targets.
Many GPCRs are classified as orphan receptors because of the limited knowledge
on their ligands and coupling to cellular signaling machineries. Here, we engineer
a library of 63 chimeric receptors that contain the signaling domains of human
orphan and understudied GPCRs functionally linked to the light-sensing domain
of rhodopsin. Upon stimulation with visible light, we identify activation of canonical
cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent
pathways, downstream of the engineered receptors. For the human pseudogene GPR33,
we resurrect a signaling function that supports its hypothesized role as a pathogen
entry site. These results demonstrate that substituting unknown chemical activators
with a light switch can reveal information about protein function and provide
an optically controlled protein library for exploring the physiology and therapeutic
potential of understudied GPCRs.
article_number: '1950'
article_processing_charge: No
author:
- first_name: Maurizio
full_name: Morri, Maurizio
id: 4863116E-F248-11E8-B48F-1D18A9856A87
last_name: Morri
- first_name: Inmaculada
full_name: Sanchez-Romero, Inmaculada
id: 3D9C5D30-F248-11E8-B48F-1D18A9856A87
last_name: Sanchez-Romero
- first_name: Alexandra-Madelaine
full_name: Tichy, Alexandra-Madelaine
id: 29D8BB2C-F248-11E8-B48F-1D18A9856A87
last_name: Tichy
- first_name: Stephanie
full_name: Kainrath, Stephanie
id: 32CFBA64-F248-11E8-B48F-1D18A9856A87
last_name: Kainrath
- first_name: Elliot J.
full_name: Gerrard, Elliot J.
last_name: Gerrard
- first_name: Priscila
full_name: Hirschfeld, Priscila
id: 435ACB3A-F248-11E8-B48F-1D18A9856A87
last_name: Hirschfeld
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- 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: Morri M, Sanchez-Romero I, Tichy A-M, et al. Optical functionalization of human
class A orphan G-protein-coupled receptors. Nature Communications. 2018;9(1).
doi:10.1038/s41467-018-04342-1
apa: Morri, M., Sanchez-Romero, I., Tichy, A.-M., Kainrath, S., Gerrard, E. J.,
Hirschfeld, P., … Janovjak, H. L. (2018). Optical functionalization of human class
A orphan G-protein-coupled receptors. Nature Communications. Springer Nature.
https://doi.org/10.1038/s41467-018-04342-1
chicago: Morri, Maurizio, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy,
Stephanie Kainrath, Elliot J. Gerrard, Priscila Hirschfeld, Jan Schwarz, and Harald
L Janovjak. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled
Receptors.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-04342-1.
ieee: M. Morri et al., “Optical functionalization of human class A orphan
G-protein-coupled receptors,” Nature Communications, vol. 9, no. 1. Springer
Nature, 2018.
ista: Morri M, Sanchez-Romero I, Tichy A-M, Kainrath S, Gerrard EJ, Hirschfeld P,
Schwarz J, Janovjak HL. 2018. Optical functionalization of human class A orphan
G-protein-coupled receptors. Nature Communications. 9(1), 1950.
mla: Morri, Maurizio, et al. “Optical Functionalization of Human Class A Orphan
G-Protein-Coupled Receptors.” Nature Communications, vol. 9, no. 1, 1950,
Springer Nature, 2018, doi:10.1038/s41467-018-04342-1.
short: M. Morri, I. Sanchez-Romero, A.-M. Tichy, S. Kainrath, E.J. Gerrard, P. Hirschfeld,
J. Schwarz, H.L. Janovjak, Nature Communications 9 (2018).
date_created: 2019-02-14T10:50:24Z
date_published: 2018-12-01T00:00:00Z
date_updated: 2023-09-19T14:29:32Z
day: '01'
ddc:
- '570'
department:
- _id: HaJa
- _id: CaGu
- _id: MiSi
doi: 10.1038/s41467-018-04342-1
ec_funded: 1
external_id:
isi:
- '000432280000006'
file:
- access_level: open_access
checksum: 8325fcc194264af4749e662a73bf66b5
content_type: application/pdf
creator: kschuh
date_created: 2019-02-14T10:58:29Z
date_updated: 2020-07-14T12:47:14Z
file_id: '5985'
file_name: 2018_Springer_Morri.pdf
file_size: 1349914
relation: main_file
file_date_updated: 2020-07-14T12:47:14Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
issue: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 25548C20-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '303564'
name: Microbial Ion Channels for Synthetic Neurobiology
- _id: 255A6082-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optical functionalization of human class A orphan G-protein-coupled receptors
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: 9
year: '2018'
...
---
_id: '19'
abstract:
- lang: eng
text: Bacteria regulate genes to survive antibiotic stress, but regulation can be
far from perfect. When regulation is not optimal, mutations that change gene expression
can contribute to antibiotic resistance. It is not systematically understood to
what extent natural gene regulation is or is not optimal for distinct antibiotics,
and how changes in expression of specific genes quantitatively affect antibiotic
resistance. Here we discover a simple quantitative relation between fitness, gene
expression, and antibiotic potency, which rationalizes our observation that a
multitude of genes and even innate antibiotic defense mechanisms have expression
that is critically nonoptimal under antibiotic treatment. First, we developed
a pooled-strain drug-diffusion assay and screened Escherichia coli overexpression
and knockout libraries, finding that resistance to a range of 31 antibiotics could
result from changing expression of a large and functionally diverse set of genes,
in a primarily but not exclusively drug-specific manner. Second, by synthetically
controlling the expression of single-drug and multidrug resistance genes, we observed
that their fitness-expression functions changed dramatically under antibiotic
treatment in accordance with a log-sensitivity relation. Thus, because many genes
are nonoptimally expressed under antibiotic treatment, many regulatory mutations
can contribute to resistance by altering expression and by activating latent defenses.
article_processing_charge: No
article_type: original
author:
- first_name: Adam
full_name: Palmer, Adam
last_name: Palmer
- 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: Roy
full_name: Kishony, Roy
last_name: Kishony
citation:
ama: Palmer A, Chait RP, Kishony R. Nonoptimal gene expression creates latent potential
for antibiotic resistance. Molecular Biology and Evolution. 2018;35(11):2669-2684.
doi:10.1093/molbev/msy163
apa: Palmer, A., Chait, R. P., & Kishony, R. (2018). Nonoptimal gene expression
creates latent potential for antibiotic resistance. Molecular Biology and Evolution.
Oxford University Press. https://doi.org/10.1093/molbev/msy163
chicago: Palmer, Adam, Remy P Chait, and Roy Kishony. “Nonoptimal Gene Expression
Creates Latent Potential for Antibiotic Resistance.” Molecular Biology and
Evolution. Oxford University Press, 2018. https://doi.org/10.1093/molbev/msy163.
ieee: A. Palmer, R. P. Chait, and R. Kishony, “Nonoptimal gene expression creates
latent potential for antibiotic resistance,” Molecular Biology and Evolution,
vol. 35, no. 11. Oxford University Press, pp. 2669–2684, 2018.
ista: Palmer A, Chait RP, Kishony R. 2018. Nonoptimal gene expression creates latent
potential for antibiotic resistance. Molecular Biology and Evolution. 35(11),
2669–2684.
mla: Palmer, Adam, et al. “Nonoptimal Gene Expression Creates Latent Potential for
Antibiotic Resistance.” Molecular Biology and Evolution, vol. 35, no. 11,
Oxford University Press, 2018, pp. 2669–84, doi:10.1093/molbev/msy163.
short: A. Palmer, R.P. Chait, R. Kishony, Molecular Biology and Evolution 35 (2018)
2669–2684.
date_created: 2018-12-11T11:44:11Z
date_published: 2018-08-28T00:00:00Z
date_updated: 2023-10-17T11:51:06Z
day: '28'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1093/molbev/msy163
external_id:
isi:
- '000452567200006'
pmid:
- '30169679'
intvolume: ' 35'
isi: 1
issue: '11'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pubmed/30169679
month: '08'
oa: 1
oa_version: Submitted Version
page: 2669 - 2684
pmid: 1
publication: Molecular Biology and Evolution
publication_identifier:
issn:
- 0737-4038
publication_status: published
publisher: Oxford University Press
publist_id: '8036'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nonoptimal gene expression creates latent potential for antibiotic resistance
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 35
year: '2018'
...
---
_id: '438'
abstract:
- lang: eng
text: The MazF toxin sequence-specifically cleaves single-stranded RNA upon various
stressful conditions, and it is activated as a part of the mazEF toxin–antitoxin
module in Escherichia coli. Although autoregulation of mazEF expression through
the MazE antitoxin-dependent transcriptional repression has been biochemically
characterized, less is known about post-transcriptional autoregulation, as well
as how both of these autoregulatory features affect growth of single cells during
conditions that promote MazF production. Here, we demonstrate post-transcriptional
autoregulation of mazF expression dynamics by MazF cleaving its own transcript.
Single-cell analyses of bacterial populations during ectopic MazF production indicated
that two-level autoregulation of mazEF expression influences cell-to-cell growth
rate heterogeneity. The increase in growth rate heterogeneity is governed by the
MazE antitoxin, and tuned by the MazF-dependent mazF mRNA cleavage. Also, both
autoregulatory features grant rapid exit from the stress caused by mazF overexpression.
Time-lapse microscopy revealed that MazF-mediated cleavage of mazF mRNA leads
to increased temporal variability in length of individual cells during ectopic
mazF overexpression, as explained by a stochastic model indicating that mazEF
mRNA cleavage underlies temporal fluctuations in MazF levels during stress.
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Nela
full_name: Nikolic, Nela
id: 42D9CABC-F248-11E8-B48F-1D18A9856A87
last_name: Nikolic
orcid: 0000-0001-9068-6090
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- first_name: Alexandra
full_name: Vandervelde, Alexandra
last_name: Vandervelde
- first_name: Tanino
full_name: Albanese, Tanino
last_name: Albanese
- first_name: Lendert
full_name: Gelens, Lendert
last_name: Gelens
- first_name: Isabella
full_name: Moll, Isabella
last_name: Moll
citation:
ama: Nikolic N, Bergmiller T, Vandervelde A, Albanese T, Gelens L, Moll I. Autoregulation
of mazEF expression underlies growth heterogeneity in bacterial populations. Nucleic
Acids Research. 2018;46(6):2918-2931. doi:10.1093/nar/gky079
apa: Nikolic, N., Bergmiller, T., Vandervelde, A., Albanese, T., Gelens, L., &
Moll, I. (2018). Autoregulation of mazEF expression underlies growth heterogeneity
in bacterial populations. Nucleic Acids Research. Oxford University Press.
https://doi.org/10.1093/nar/gky079
chicago: Nikolic, Nela, Tobias Bergmiller, Alexandra Vandervelde, Tanino Albanese,
Lendert Gelens, and Isabella Moll. “Autoregulation of MazEF Expression Underlies
Growth Heterogeneity in Bacterial Populations.” Nucleic Acids Research.
Oxford University Press, 2018. https://doi.org/10.1093/nar/gky079.
ieee: N. Nikolic, T. Bergmiller, A. Vandervelde, T. Albanese, L. Gelens, and I.
Moll, “Autoregulation of mazEF expression underlies growth heterogeneity in bacterial
populations,” Nucleic Acids Research, vol. 46, no. 6. Oxford University
Press, pp. 2918–2931, 2018.
ista: Nikolic N, Bergmiller T, Vandervelde A, Albanese T, Gelens L, Moll I. 2018.
Autoregulation of mazEF expression underlies growth heterogeneity in bacterial
populations. Nucleic Acids Research. 46(6), 2918–2931.
mla: Nikolic, Nela, et al. “Autoregulation of MazEF Expression Underlies Growth
Heterogeneity in Bacterial Populations.” Nucleic Acids Research, vol. 46,
no. 6, Oxford University Press, 2018, pp. 2918–31, doi:10.1093/nar/gky079.
short: N. Nikolic, T. Bergmiller, A. Vandervelde, T. Albanese, L. Gelens, I. Moll,
Nucleic Acids Research 46 (2018) 2918–2931.
date_created: 2018-12-11T11:46:29Z
date_published: 2018-04-06T00:00:00Z
date_updated: 2024-02-21T13:44:45Z
day: '06'
ddc:
- '576'
department:
- _id: CaGu
doi: 10.1093/nar/gky079
external_id:
isi:
- '000429009500021'
file:
- access_level: open_access
checksum: 3ff4f545c27e11a4cd20ccb30778793e
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:15:30Z
date_updated: 2020-07-14T12:46:27Z
file_id: '5151'
file_name: IST-2018-971-v1+1_2018_Nikoloc_Autoregulation_of.pdf
file_size: 5027978
relation: main_file
file_date_updated: 2020-07-14T12:46:27Z
has_accepted_license: '1'
intvolume: ' 46'
isi: 1
issue: '6'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 2918-2931
project:
- _id: 3AC91DDA-15DF-11EA-824D-93A3E7B544D1
call_identifier: FWF
name: FWF Open Access Fund
publication: Nucleic Acids Research
publication_status: published
publisher: Oxford University Press
pubrep_id: '971'
quality_controlled: '1'
related_material:
record:
- id: '5569'
relation: popular_science
status: public
scopus_import: '1'
status: public
title: Autoregulation of mazEF expression underlies growth heterogeneity in bacterial
populations
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: 46
year: '2018'
...
---
_id: '5569'
abstract:
- lang: eng
text: "Nela Nikolic, Tobias Bergmiller, Alexandra Vandervelde, Tanino G. Albanese,
Lendert Gelens, and Isabella Moll (2018)\r\n“Autoregulation of mazEF expression
underlies growth heterogeneity in bacterial populations” Nucleic Acids Research,
doi: 10.15479/AT:ISTA:74;\r\nmicroscopy experiments by Tobias Bergmiller; image
and data analysis by Nela Nikolic."
article_processing_charge: No
author:
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
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full_name: Nikolic, Nela
id: 42D9CABC-F248-11E8-B48F-1D18A9856A87
last_name: Nikolic
orcid: 0000-0001-9068-6090
citation:
ama: Bergmiller T, Nikolic N. Time-lapse microscopy data. 2018. doi:10.15479/AT:ISTA:74
apa: Bergmiller, T., & Nikolic, N. (2018). Time-lapse microscopy data. Institute
of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:74
chicago: Bergmiller, Tobias, and Nela Nikolic. “Time-Lapse Microscopy Data.” Institute
of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:74.
ieee: T. Bergmiller and N. Nikolic, “Time-lapse microscopy data.” Institute of Science
and Technology Austria, 2018.
ista: Bergmiller T, Nikolic N. 2018. Time-lapse microscopy data, Institute of Science
and Technology Austria, 10.15479/AT:ISTA:74.
mla: Bergmiller, Tobias, and Nela Nikolic. Time-Lapse Microscopy Data. Institute
of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:74.
short: T. Bergmiller, N. Nikolic, (2018).
datarep_id: '74'
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date_published: 2018-02-07T00:00:00Z
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month: '02'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
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related_material:
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title: Time-lapse microscopy data
tmp:
image: /images/cc_0.png
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year: '2018'
...
---
_id: '161'
abstract:
- lang: eng
text: 'Which properties of metabolic networks can be derived solely from stoichiometry?
Predictive results have been obtained by flux balance analysis (FBA), by postulating
that cells set metabolic fluxes to maximize growth rate. Here we consider a generalization
of FBA to single-cell level using maximum entropy modeling, which we extend and
test experimentally. Specifically, we define for Escherichia coli metabolism a
flux distribution that yields the experimental growth rate: the model, containing
FBA as a limit, provides a better match to measured fluxes and it makes a wide
range of predictions: on flux variability, regulation, and correlations; on the
relative importance of stoichiometry vs. optimization; on scaling relations for
growth rate distributions. We validate the latter here with single-cell data at
different sub-inhibitory antibiotic concentrations. The model quantifies growth
optimization as emerging from the interplay of competitive dynamics in the population
and regulation of metabolism at the level of single cells.'
article_number: '2988'
article_processing_charge: No
author:
- first_name: Daniele
full_name: De Martino, Daniele
id: 3FF5848A-F248-11E8-B48F-1D18A9856A87
last_name: De Martino
orcid: 0000-0002-5214-4706
- first_name: Andersson Anna
full_name: Mc, Andersson Anna
last_name: Mc
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- 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: Gasper
full_name: Tkacik, Gasper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkacik
orcid: 0000-0002-6699-1455
citation:
ama: De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. Statistical mechanics
for metabolic networks during steady state growth. Nature Communications.
2018;9(1). doi:10.1038/s41467-018-05417-9
apa: De Martino, D., Mc, A. A., Bergmiller, T., Guet, C. C., & Tkačik, G. (2018).
Statistical mechanics for metabolic networks during steady state growth. Nature
Communications. Springer Nature. https://doi.org/10.1038/s41467-018-05417-9
chicago: De Martino, Daniele, Andersson Anna Mc, Tobias Bergmiller, Calin C Guet,
and Gašper Tkačik. “Statistical Mechanics for Metabolic Networks during Steady
State Growth.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-05417-9.
ieee: D. De Martino, A. A. Mc, T. Bergmiller, C. C. Guet, and G. Tkačik, “Statistical
mechanics for metabolic networks during steady state growth,” Nature Communications,
vol. 9, no. 1. Springer Nature, 2018.
ista: De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. 2018. Statistical mechanics
for metabolic networks during steady state growth. Nature Communications. 9(1),
2988.
mla: De Martino, Daniele, et al. “Statistical Mechanics for Metabolic Networks during
Steady State Growth.” Nature Communications, vol. 9, no. 1, 2988, Springer
Nature, 2018, doi:10.1038/s41467-018-05417-9.
short: D. De Martino, A.A. Mc, T. Bergmiller, C.C. Guet, G. Tkačik, Nature Communications
9 (2018).
date_created: 2018-12-11T11:44:57Z
date_published: 2018-07-30T00:00:00Z
date_updated: 2024-02-21T13:45:39Z
day: '30'
ddc:
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department:
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call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
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publication: Nature Communications
publication_status: published
publisher: Springer Nature
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scopus_import: '1'
status: public
title: Statistical mechanics for metabolic networks during steady state growth
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
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volume: 9
year: '2018'
...
---
_id: '26'
abstract:
- lang: eng
text: Expression of genes is a fundamental molecular phenotype that is subject to
evolution by different types of mutations. Both the rate and the effect of mutations
may depend on the DNA sequence context of a particular gene or a particular promoter
sequence. In this thesis I investigate the nature of this dependence using simple
genetic systems in Escherichia coli. With these systems I explore the evolution
of constitutive gene expression from random starting sequences at different loci
on the chromosome and at different locations in sequence space. First, I dissect
chromosomal neighborhood effects that underlie locus-dependent differences in
the potential of a gene under selection to become more highly expressed. Next,
I find that the effects of point mutations in promoter sequences are dependent
on sequence context, and that an existing energy matrix model performs poorly
in predicting relative expression of unrelated sequences. Finally, I show that
a substantial fraction of random sequences contain functional promoters and I
present an extended thermodynamic model that predicts promoter strength in full
sequence space. Taken together, these results provide new insights and guides
on how to integrate information on sequence context to improve our qualitative
and quantitative understanding of bacterial gene expression, with implications
for rapid evolution of drug resistance, de novo evolution of genes, and horizontal
gene transfer.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
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full_name: Steinrück, Magdalena
id: 2C023F40-F248-11E8-B48F-1D18A9856A87
last_name: Steinrück
orcid: 0000-0003-1229-9719
citation:
ama: Steinrück M. The influence of sequence context on the evolution of bacterial
gene expression. 2018. doi:10.15479/AT:ISTA:th1059
apa: Steinrück, M. (2018). The influence of sequence context on the evolution
of bacterial gene expression. Institute of Science and Technology Austria.
https://doi.org/10.15479/AT:ISTA:th1059
chicago: Steinrück, Magdalena. “The Influence of Sequence Context on the Evolution
of Bacterial Gene Expression.” Institute of Science and Technology Austria, 2018.
https://doi.org/10.15479/AT:ISTA:th1059.
ieee: M. Steinrück, “The influence of sequence context on the evolution of bacterial
gene expression,” Institute of Science and Technology Austria, 2018.
ista: Steinrück M. 2018. The influence of sequence context on the evolution of bacterial
gene expression. Institute of Science and Technology Austria.
mla: Steinrück, Magdalena. The Influence of Sequence Context on the Evolution
of Bacterial Gene Expression. Institute of Science and Technology Austria,
2018, doi:10.15479/AT:ISTA:th1059.
short: M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial
Gene Expression, Institute of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:44:14Z
date_published: 2018-10-30T00:00:00Z
date_updated: 2023-09-07T12:48:43Z
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issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8029'
pubrep_id: '1059'
related_material:
record:
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relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
title: The influence of sequence context on the evolution of bacterial gene expression
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '67'
abstract:
- lang: eng
text: 'Gene regulatory networks evolve through rewiring of individual components—that
is, through changes in regulatory connections. However, the mechanistic basis
of regulatory rewiring is poorly understood. Using a canonical gene regulatory
system, we quantify the properties of transcription factors that determine the
evolutionary potential for rewiring of regulatory connections: robustness, tunability
and evolvability. In vivo repression measurements of two repressors at mutated
operator sites reveal their contrasting evolutionary potential: while robustness
and evolvability were positively correlated, both were in trade-off with tunability.
Epistatic interactions between adjacent operators alleviated this trade-off. A
thermodynamic model explains how the differences in robustness, tunability and
evolvability arise from biophysical characteristics of repressor–DNA binding.
The model also uncovers that the energy matrix, which describes how mutations
affect repressor–DNA binding, encodes crucial information about the evolutionary
potential of a repressor. The biophysical determinants of evolutionary potential
for regulatory rewiring constitute a mechanistic framework for understanding network
evolution.'
article_processing_charge: No
article_type: original
author:
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Gasper
full_name: Tkacik, Gasper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkacik
orcid: 0000-0002-6699-1455
- 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: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential
of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution.
2018;2(10):1633-1643. doi:10.1038/s41559-018-0651-y
apa: Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018).
Evolutionary potential of transcription factors for gene regulatory rewiring.
Nature Ecology and Evolution. Nature Publishing Group. https://doi.org/10.1038/s41559-018-0651-y
chicago: Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin
C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.”
Nature Ecology and Evolution. Nature Publishing Group, 2018. https://doi.org/10.1038/s41559-018-0651-y.
ieee: C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary
potential of transcription factors for gene regulatory rewiring,” Nature Ecology
and Evolution, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018.
ista: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential
of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution.
2(10), 1633–1643.
mla: Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for
Gene Regulatory Rewiring.” Nature Ecology and Evolution, vol. 2, no. 10,
Nature Publishing Group, 2018, pp. 1633–43, doi:10.1038/s41559-018-0651-y.
short: C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology
and Evolution 2 (2018) 1633–1643.
date_created: 2018-12-11T11:44:27Z
date_published: 2018-09-10T00:00:00Z
date_updated: 2024-03-28T23:30:49Z
day: '10'
ddc:
- '570'
department:
- _id: CaGu
- _id: GaTk
- _id: JoBo
doi: 10.1038/s41559-018-0651-y
ec_funded: 1
external_id:
isi:
- '000447947600021'
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content_type: application/pdf
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isi: 1
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language:
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month: '09'
oa: 1
oa_version: Submitted Version
page: 1633 - 1643
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 2578D616-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
grant_number: '24573'
name: Design principles underlying genetic switch architecture (DOC Fellowship)
publication: Nature Ecology and Evolution
publication_status: published
publisher: Nature Publishing Group
publist_id: '7987'
quality_controlled: '1'
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record:
- id: '5585'
relation: popular_science
status: public
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relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Evolutionary potential of transcription factors for gene regulatory rewiring
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 2
year: '2018'
...
---
_id: '5585'
abstract:
- lang: eng
text: Mean repression values and standard error of the mean are given for all operator
mutant libraries.
article_processing_charge: No
author:
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Gasper
full_name: Tkacik, Gasper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkacik
orcid: 0000-0002-6699-1455
- 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: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Data for the paper Evolutionary
potential of transcription factors for gene regulatory rewiring. 2018. doi:10.15479/AT:ISTA:108
apa: Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018).
Data for the paper Evolutionary potential of transcription factors for gene regulatory
rewiring. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:108
chicago: Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin
C Guet. “Data for the Paper Evolutionary Potential of Transcription Factors for
Gene Regulatory Rewiring.” Institute of Science and Technology Austria, 2018.
https://doi.org/10.15479/AT:ISTA:108.
ieee: C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Data for
the paper Evolutionary potential of transcription factors for gene regulatory
rewiring.” Institute of Science and Technology Austria, 2018.
ista: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Data for the paper
Evolutionary potential of transcription factors for gene regulatory rewiring,
Institute of Science and Technology Austria, 10.15479/AT:ISTA:108.
mla: Igler, Claudia, et al. Data for the Paper Evolutionary Potential of Transcription
Factors for Gene Regulatory Rewiring. Institute of Science and Technology
Austria, 2018, doi:10.15479/AT:ISTA:108.
short: C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, (2018).
datarep_id: '108'
date_created: 2018-12-12T12:31:40Z
date_published: 2018-07-20T00:00:00Z
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- _id: GaTk
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ec_funded: 1
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month: '07'
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
- _id: 2578D616-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
grant_number: '24573'
name: Design principles underlying genetic switch architecture (DOC Fellowship)
publisher: Institute of Science and Technology Austria
related_material:
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relation: research_paper
status: public
- id: '6371'
relation: research_paper
status: public
status: public
title: Data for the paper Evolutionary potential of transcription factors for gene
regulatory rewiring
tmp:
image: /images/cc_0.png
legal_code_url: https://creativecommons.org/publicdomain/zero/1.0/legalcode
name: Creative Commons Public Domain Dedication (CC0 1.0)
short: CC0 (1.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2018'
...
---
_id: '538'
abstract:
- lang: ger
text: 'Optogenetik und Photopharmakologie ermöglichen präzise räumliche und zeitliche
Kontrolle von Proteinwechselwirkung und -funktion in Zellen und Tieren. Optogenetische
Methoden, die auf grünes Licht ansprechen und zum Trennen von Proteinkomplexen
geeignet sind, sind nichtweitläufig verfügbar, würden jedoch mehrfarbige Experimente
zur Beantwortung von biologischen Fragestellungen ermöglichen. Hier demonstrieren
wir die Verwendung von Cobalamin(Vitamin B12)-bindenden Domänen von bakteriellen
CarH-Transkriptionsfaktoren zur Grünlicht-induzierten Dissoziation von Rezeptoren.
Fusioniert mit dem Fibroblasten-W achstumsfaktor-Rezeptor 1 führten diese im Dunkeln
in kultivierten Zellen zu Signalaktivität durch Oligomerisierung, welche durch
Beleuchten umgehend aufgehoben wurde. In Zebrafischembryonen, die einen derartigen
Rezeptor exprimieren, ermöglichte grünes Licht die Kontrolle über abnormale Signalaktivität
während der Embryonalentwicklung. '
author:
- first_name: Stephanie
full_name: Kainrath, Stephanie
id: 32CFBA64-F248-11E8-B48F-1D18A9856A87
last_name: Kainrath
- first_name: Manuela
full_name: Stadler, Manuela
last_name: Stadler
- first_name: Eva
full_name: Gschaider-Reichhart, Eva
id: 3FEE232A-F248-11E8-B48F-1D18A9856A87
last_name: Gschaider-Reichhart
orcid: 0000-0002-7218-7738
- first_name: Martin
full_name: Distel, Martin
last_name: Distel
- 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, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. Grünlicht-induzierte
Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte Chemie.
2017;129(16):4679-4682. doi:10.1002/ange.201611998
apa: Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., & Janovjak,
H. L. (2017). Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende
Domänen. Angewandte Chemie. Wiley. https://doi.org/10.1002/ange.201611998
chicago: Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel,
and Harald L Janovjak. “Grünlicht-Induzierte Rezeptorinaktivierung Durch Cobalamin-Bindende
Domänen.” Angewandte Chemie. Wiley, 2017. https://doi.org/10.1002/ange.201611998.
ieee: S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak,
“Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen,”
Angewandte Chemie, vol. 129, no. 16. Wiley, pp. 4679–4682, 2017.
ista: Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017.
Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte
Chemie. 129(16), 4679–4682.
mla: Kainrath, Stephanie, et al. “Grünlicht-Induzierte Rezeptorinaktivierung Durch
Cobalamin-Bindende Domänen.” Angewandte Chemie, vol. 129, no. 16, Wiley,
2017, pp. 4679–82, doi:10.1002/ange.201611998.
short: S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak,
Angewandte Chemie 129 (2017) 4679–4682.
date_created: 2018-12-11T11:47:02Z
date_published: 2017-05-20T00:00:00Z
date_updated: 2021-01-12T08:01:33Z
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department:
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- _id: HaJa
doi: 10.1002/ange.201611998
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title: Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen
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