---
_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).
corr_author: '1'
date_created: 2022-08-01T09:04:27Z
date_published: 2022-05-13T00:00:00Z
date_updated: 2025-04-14T09:24:53Z
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: '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
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: 0000-0002-6620-9179
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).
corr_author: '1'
date_created: 2022-08-14T22:01:46Z
date_published: 2022-07-26T00:00:00Z
date_updated: 2025-04-15T07:17:32Z
day: '26'
ddc:
- '570'
department:
- _id: MiSi
- _id: CaGu
doi: 10.7554/eLife.78995
ec_funded: 1
external_id:
isi:
- '000838410200001'
pmid:
- '35881547'
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
pmid: 1
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
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).
corr_author: '1'
date_created: 2023-01-22T23:00:55Z
date_published: 2022-12-22T00:00:00Z
date_updated: 2025-03-06T14:03:50Z
day: '22'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.7554/ELIFE.82240
external_id:
isi:
- '000912674700001'
pmid:
- '36546673'
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
pmid: 1
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
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).
corr_author: '1'
date_created: 2023-01-23T09:00:37Z
date_published: 2022-12-23T00:00:00Z
date_updated: 2025-03-06T14:03:50Z
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: '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: Steinrück, Magdalena
id: 2C023F40-F248-11E8-B48F-1D18A9856A87
last_name: Steinrück
orcid: 0000-0003-1229-9719
- 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, Steinrück 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., Steinrück, 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 Steinrück, 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, Steinrück 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. Steinrück, D. Toledo-Aparicio, J.P. Bollback,
C.C. Guet, G. Tkačik, ELife 11 (2022).
corr_author: '1'
date_created: 2022-02-06T23:01:32Z
date_published: 2022-01-26T00:00:00Z
date_updated: 2025-03-31T16:00:23Z
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
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: '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: 2025-09-09T14:29:53Z
day: '18'
ddc:
- '570'
- '000'
department:
- _id: CaGu
doi: 10.1371/journal.pcbi.1009950
external_id:
isi:
- '001044208400004'
pmid:
- '35303737'
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'
isi: 1
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 18
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: '15270'
abstract:
- lang: eng
text: Various toxic compounds disrupt bacterial physiology. While bacteria harbor
defense mechanisms to mitigate the toxicity, these mechanisms are often coupled
to the physiological state of the cells and become ineffective when the physiology
is severely disrupted.
article_number: '676'
article_processing_charge: Yes
article_type: original
author:
- first_name: Dai
full_name: Le, Dai
last_name: Le
- first_name: Ekaterina
full_name: Krasnopeeva, Ekaterina
id: 1F1EE44A-BF83-11EA-B3C1-BB9CC619BF3A
last_name: Krasnopeeva
- first_name: Faris
full_name: Sinjab, Faris
last_name: Sinjab
- first_name: Teuta
full_name: Pilizota, Teuta
last_name: Pilizota
- first_name: Minsu
full_name: Kim, Minsu
last_name: Kim
citation:
ama: Le D, Krasnopeeva E, Sinjab F, Pilizota T, Kim M. Active efflux leads to heterogeneous
dissipation of proton motive force by protonophores in bacteria. mBio.
2021;12(4). doi:10.1128/mbio.00676-21
apa: Le, D., Krasnopeeva, E., Sinjab, F., Pilizota, T., & Kim, M. (2021). Active
efflux leads to heterogeneous dissipation of proton motive force by protonophores
in bacteria. MBio. American Society for Microbiology. https://doi.org/10.1128/mbio.00676-21
chicago: Le, Dai, Ekaterina Krasnopeeva, Faris Sinjab, Teuta Pilizota, and Minsu
Kim. “Active Efflux Leads to Heterogeneous Dissipation of Proton Motive Force
by Protonophores in Bacteria.” MBio. American Society for Microbiology,
2021. https://doi.org/10.1128/mbio.00676-21.
ieee: D. Le, E. Krasnopeeva, F. Sinjab, T. Pilizota, and M. Kim, “Active efflux
leads to heterogeneous dissipation of proton motive force by protonophores in
bacteria,” mBio, vol. 12, no. 4. American Society for Microbiology, 2021.
ista: Le D, Krasnopeeva E, Sinjab F, Pilizota T, Kim M. 2021. Active efflux leads
to heterogeneous dissipation of proton motive force by protonophores in bacteria.
mBio. 12(4), 676.
mla: Le, Dai, et al. “Active Efflux Leads to Heterogeneous Dissipation of Proton
Motive Force by Protonophores in Bacteria.” MBio, vol. 12, no. 4, 676,
American Society for Microbiology, 2021, doi:10.1128/mbio.00676-21.
short: D. Le, E. Krasnopeeva, F. Sinjab, T. Pilizota, M. Kim, MBio 12 (2021).
date_created: 2024-04-03T07:51:57Z
date_published: 2021-08-31T00:00:00Z
date_updated: 2024-04-10T09:13:59Z
day: '31'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1128/mbio.00676-21
external_id:
pmid:
- '34253054'
file:
- access_level: open_access
checksum: 529e3f97ae5c5f5cc743c4fc130c9440
content_type: application/pdf
creator: dernst
date_created: 2024-04-10T09:05:49Z
date_updated: 2024-04-10T09:05:49Z
file_id: '15309'
file_name: 2021_mBio_Le.pdf
file_size: 1344204
relation: main_file
success: 1
file_date_updated: 2024-04-10T09:05:49Z
has_accepted_license: '1'
intvolume: ' 12'
issue: '4'
keyword:
- Virology
- Microbiology
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: mBio
publication_identifier:
issn:
- 2150-7511
publication_status: published
publisher: American Society for Microbiology
quality_controlled: '1'
status: public
title: Active efflux leads to heterogeneous dissipation of proton motive force by
protonophores in bacteria
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2021'
...
---
_id: '10363'
abstract:
- lang: eng
text: Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death,
but its pro-thrombotic activity is problematic for use of erythropoietin in treating
hypoxia. We constructed a fusion protein that stimulates red blood cell production
and neuroprotection without triggering platelet production, a marker for thrombosis.
The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant
(L108A). The mutation reduces activation of erythropoietin receptor homodimers
that induce erythropoiesis and thrombosis, but maintains the tissue-protective
signaling. The binding of the nanobody element to glycophorin A rescues homodimeric
erythropoietin receptor activation on red blood cell precursors. In a cell proliferation
assay, the fusion protein is active at 10−14 M, allowing an estimate of the number
of receptor–ligand complexes needed for signaling. This fusion protein stimulates
erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity
in vitro. Our erythropoietin fusion protein presents a novel molecule for treating
hypoxia.
acknowledgement: This work was supported by funds from the Wyss Institute for Biologically
Inspired Engineering and the Boston Biomedical Innovation Center (Pilot Award 112475;
Drive Award U54HL119145). J.L., K.M.K., D.R.B., J.C.W. and P.A.S. were supported
by the Harvard Medical School Department of Systems Biology. J.C.W. was further
supported by the Harvard Medical School Laboratory of Systems Pharmacology. A.V.,
D.R.B. and P.A.S. were further supported by the Wyss Institute for Biologically
Inspired Engineering. N.G.G. was sponsored by the Army Research Office under Grant
Number W911NF-17-2-0092. The views and conclusions contained in this document are
those of the authors and should not be interpreted as representing the official
policies, either expressed or implied, of the Army Research Office or the U.S. Government.
The U.S. Government is authorized to reproduce and distribute reprints for Government
purposes notwithstanding any copyright notation herein. We sincerely thank Amanda
Graveline and the Wyss Institute at Harvard for their scientific support.
article_number: gzab025
article_processing_charge: No
article_type: original
author:
- first_name: Jungmin
full_name: Lee, Jungmin
last_name: Lee
- first_name: Andyna
full_name: Vernet, Andyna
last_name: Vernet
- first_name: Nathalie
full_name: Gruber, Nathalie
id: 2C9C8316-AA17-11E9-B5C2-8BC2E5697425
last_name: Gruber
- first_name: Kasia M.
full_name: Kready, Kasia M.
last_name: Kready
- first_name: Devin R.
full_name: Burrill, Devin R.
last_name: Burrill
- first_name: Jeffrey C.
full_name: Way, Jeffrey C.
last_name: Way
- first_name: Pamela A.
full_name: Silver, Pamela A.
last_name: Silver
citation:
ama: Lee J, Vernet A, Gruber N, et al. Rational engineering of an erythropoietin
fusion protein to treat hypoxia. Protein Engineering, Design and Selection.
2021;34. doi:10.1093/protein/gzab025
apa: Lee, J., Vernet, A., Gruber, N., Kready, K. M., Burrill, D. R., Way, J. C.,
& Silver, P. A. (2021). Rational engineering of an erythropoietin fusion protein
to treat hypoxia. Protein Engineering, Design and Selection. Oxford University
Press. https://doi.org/10.1093/protein/gzab025
chicago: Lee, Jungmin, Andyna Vernet, Nathalie Gruber, Kasia M. Kready, Devin R.
Burrill, Jeffrey C. Way, and Pamela A. Silver. “Rational Engineering of an Erythropoietin
Fusion Protein to Treat Hypoxia.” Protein Engineering, Design and Selection.
Oxford University Press, 2021. https://doi.org/10.1093/protein/gzab025.
ieee: J. Lee et al., “Rational engineering of an erythropoietin fusion protein
to treat hypoxia,” Protein Engineering, Design and Selection, vol. 34.
Oxford University Press, 2021.
ista: Lee J, Vernet A, Gruber N, Kready KM, Burrill DR, Way JC, Silver PA. 2021.
Rational engineering of an erythropoietin fusion protein to treat hypoxia. Protein
Engineering, Design and Selection. 34, gzab025.
mla: Lee, Jungmin, et al. “Rational Engineering of an Erythropoietin Fusion Protein
to Treat Hypoxia.” Protein Engineering, Design and Selection, vol. 34,
gzab025, Oxford University Press, 2021, doi:10.1093/protein/gzab025.
short: J. Lee, A. Vernet, N. Gruber, K.M. Kready, D.R. Burrill, J.C. Way, P.A. Silver,
Protein Engineering, Design and Selection 34 (2021).
date_created: 2021-11-28T23:01:28Z
date_published: 2021-11-01T00:00:00Z
date_updated: 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: '9046'
acknowledgement: Our work was supported by the Swedish Research Council (grant 2017-01527)
to DIA
article_number: e1009172
article_processing_charge: No
article_type: original
author:
- first_name: Roderich
full_name: Römhild, Roderich
id: 68E56E44-62B0-11EA-B963-444F3DDC885E
last_name: Römhild
orcid: 0000-0001-9480-5261
- first_name: Dan I.
full_name: Andersson, Dan I.
last_name: Andersson
citation:
ama: Römhild R, Andersson DI. Mechanisms and therapeutic potential of collateral
sensitivity to antibiotics. PLoS Pathogens. 2021;17(1). doi:10.1371/journal.ppat.1009172
apa: Römhild, R., & Andersson, D. I. (2021). Mechanisms and therapeutic potential
of collateral sensitivity to antibiotics. PLoS Pathogens. Public Library
of Science. https://doi.org/10.1371/journal.ppat.1009172
chicago: Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential
of Collateral Sensitivity to Antibiotics.” PLoS Pathogens. Public Library
of Science, 2021. https://doi.org/10.1371/journal.ppat.1009172.
ieee: R. Römhild and D. I. Andersson, “Mechanisms and therapeutic potential of collateral
sensitivity to antibiotics,” PLoS Pathogens, vol. 17, no. 1. Public Library
of Science, 2021.
ista: Römhild R, Andersson DI. 2021. Mechanisms and therapeutic potential of collateral
sensitivity to antibiotics. PLoS Pathogens. 17(1), e1009172.
mla: Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential
of Collateral Sensitivity to Antibiotics.” PLoS Pathogens, vol. 17, no.
1, e1009172, Public Library of Science, 2021, doi:10.1371/journal.ppat.1009172.
short: R. Römhild, D.I. Andersson, PLoS Pathogens 17 (2021).
date_created: 2021-01-31T23:01:21Z
date_published: 2021-01-14T00:00:00Z
date_updated: 2025-07-10T12:01:33Z
day: '14'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1371/journal.ppat.1009172
external_id:
isi:
- '000610190400007'
pmid:
- '33444399'
file:
- access_level: open_access
checksum: d745d7f8fcbb9b95fea16a36f94dee31
content_type: application/pdf
creator: dernst
date_created: 2021-02-03T12:13:03Z
date_updated: 2021-02-03T12:13:03Z
file_id: '9070'
file_name: 2021_PlosPathogens_Roemhild.pdf
file_size: 570066
relation: main_file
success: 1
file_date_updated: 2021-02-03T12:13:03Z
has_accepted_license: '1'
intvolume: ' 17'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
publication: PLoS Pathogens
publication_identifier:
eissn:
- 1553-7374
issn:
- 1553-7366
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mechanisms and therapeutic potential of collateral sensitivity to antibiotics
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2021'
...
---
_id: '9283'
abstract:
- lang: eng
text: Gene expression levels are influenced by multiple coexisting molecular mechanisms.
Some of these interactions such as those of transcription factors and promoters
have been studied extensively. However, predicting phenotypes of gene regulatory
networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic
GRN to study in Escherichia coli how network phenotypes depend on local genetic
context, i.e. the genetic neighborhood of a transcription factor and its relative
position. We show that one GRN with fixed topology can display not only quantitatively
but also qualitatively different phenotypes, depending solely on the local genetic
context of its components. Transcriptional read-through is the main molecular
mechanism that places one transcriptional unit (TU) within two separate regulons
without the need for complex regulatory sequences. We propose that relative order
of individual TUs, with its potential for combinatorial complexity, plays an important
role in shaping phenotypes of GRNs.
acknowledgement: "We thank J Bollback, L Hurst, M Lagator, C Nizak, O Rivoire, M Savageau,
G Tkacik, and B Vicozo\r\nfor helpful discussions; A Dolinar and A Greshnova for
technical assistance; T Bollenbach for supplying the strain JW0336; C Rusnac, and
members of the Guet lab for comments. The research leading to these results has
received funding from the People Programme (Marie Curie Actions) of the European
Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n˚\r\n628377
(ANS) and an Austrian Science Fund (FWF) grant n˚ I 3901-B32 (CCG)."
article_number: e65993
article_processing_charge: Yes
article_type: original
author:
- first_name: Anna A
full_name: Nagy-Staron, Anna A
id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
last_name: Nagy-Staron
orcid: 0000-0002-1391-8377
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
- first_name: Caroline
full_name: Caruso Carter, Caroline
last_name: Caruso Carter
- first_name: Elisabeth
full_name: Sonnleitner, Elisabeth
last_name: Sonnleitner
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: Tiago
full_name: Paixão, Tiago
last_name: Paixão
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Nagy-Staron AA, Tomasek K, Caruso Carter C, et al. Local genetic context shapes
the function of a gene regulatory network. eLife. 2021;10. doi:10.7554/elife.65993
apa: Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic,
B., Paixão, T., & Guet, C. C. (2021). Local genetic context shapes the function
of a gene regulatory network. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.65993
chicago: Nagy-Staron, Anna A, Kathrin Tomasek, Caroline Caruso Carter, Elisabeth
Sonnleitner, Bor Kavcic, Tiago Paixão, and Calin C Guet. “Local Genetic Context
Shapes the Function of a Gene Regulatory Network.” ELife. eLife Sciences
Publications, 2021. https://doi.org/10.7554/elife.65993.
ieee: A. A. Nagy-Staron et al., “Local genetic context shapes the function
of a gene regulatory network,” eLife, vol. 10. eLife Sciences Publications,
2021.
ista: Nagy-Staron AA, Tomasek K, Caruso Carter C, Sonnleitner E, Kavcic B, Paixão
T, Guet CC. 2021. Local genetic context shapes the function of a gene regulatory
network. eLife. 10, e65993.
mla: Nagy-Staron, Anna A., et al. “Local Genetic Context Shapes the Function of
a Gene Regulatory Network.” ELife, vol. 10, e65993, eLife Sciences Publications,
2021, doi:10.7554/elife.65993.
short: A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic,
T. Paixão, C.C. Guet, ELife 10 (2021).
corr_author: '1'
date_created: 2021-03-23T10:11:46Z
date_published: 2021-03-08T00:00:00Z
date_updated: 2025-06-12T06:36:17Z
day: '08'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.7554/elife.65993
ec_funded: 1
external_id:
isi:
- '000631050900001'
pmid:
- '33683203'
file:
- access_level: open_access
checksum: 3c2f44058c2dd45a5a1027f09d263f8e
content_type: application/pdf
creator: bkavcic
date_created: 2021-03-23T10:12:58Z
date_updated: 2021-03-23T10:12:58Z
file_id: '9284'
file_name: elife-65993-v2.pdf
file_size: 1390469
relation: main_file
success: 1
file_date_updated: 2021-03-23T10:12:58Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
keyword:
- Genetics and Molecular Biology
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2517526A-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '628377'
name: 'The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic
Networks to Genomic Studies'
- _id: 268BFA92-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03901
name: Cybergenetic circuits to test composability of gene networks
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
record:
- id: '8951'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Local genetic context shapes the function of a gene regulatory network
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 10
year: '2021'
...
---
_id: '9647'
abstract:
- lang: eng
text: 'Gene expression is regulated by the set of transcription factors (TFs) that
bind to the promoter. The ensuing regulating function is often represented as
a combinational logic circuit, where output (gene expression) is determined by
current input values (promoter bound TFs) only. However, the simultaneous arrival
of TFs is a strong assumption, since transcription and translation of genes introduce
intrinsic time delays and there is no global synchronisation among the arrival
times of different molecular species at their targets. We present an experimentally
implementable genetic circuit with two inputs and one output, which in the presence
of small delays in input arrival, exhibits qualitatively distinct population-level
phenotypes, over timescales that are longer than typical cell doubling times.
From a dynamical systems point of view, these phenotypes represent long-lived
transients: although they converge to the same value eventually, they do so after
a very long time span. The key feature of this toy model genetic circuit is that,
despite having only two inputs and one output, it is regulated by twenty-three
distinct DNA-TF configurations, two of which are more stable than others (DNA
looped states), one promoting and another blocking the expression of the output
gene. Small delays in input arrival time result in a majority of cells in the
population quickly reaching the stable state associated with the first input,
while exiting of this stable state occurs at a slow timescale. In order to mechanistically
model the behaviour of this genetic circuit, we used a rule-based modelling language,
and implemented a grid-search to find parameter combinations giving rise to long-lived
transients. Our analysis shows that in the absence of feedback, there exist path-dependent
gene regulatory mechanisms based on the long timescale of transients. The behaviour
of this toy model circuit suggests that gene regulatory networks can exploit event
timing to create phenotypes, and it opens the possibility that they could use
event timing to memorise events, without regulatory feedback. The model reveals
the importance of (i) mechanistically modelling the transitions between the different
DNA-TF states, and (ii) employing transient analysis thereof.'
acknowledgement: 'Tatjana Petrov’s research was supported in part by SNSF Advanced
Postdoctoral Mobility Fellowship grant number P300P2 161067, the Ministry of Science,
Research and the Arts of the state of Baden-Wurttemberg, and the DFG Centre of Excellence
2117 ‘Centre for the Advanced Study of Collective Behaviour’ (ID: 422037984). Claudia
Igler is the recipient of a DOC Fellowship of the Austrian Academy of Sciences.
Thomas A. Henzinger’s research was supported in part by the Austrian Science Fund
(FWF) under grant Z211-N23 (Wittgenstein Award).'
article_processing_charge: No
article_type: original
author:
- first_name: Tatjana
full_name: Petrov, Tatjana
last_name: Petrov
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
- first_name: Ali
full_name: Sezgin, Ali
id: 4C7638DA-F248-11E8-B48F-1D18A9856A87
last_name: Sezgin
- first_name: Thomas A
full_name: Henzinger, Thomas A
id: 40876CD8-F248-11E8-B48F-1D18A9856A87
last_name: Henzinger
orcid: 0000-0002-2985-7724
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. Long lived transients in
gene regulation. Theoretical Computer Science. 2021;893:1-16. doi:10.1016/j.tcs.2021.05.023
apa: Petrov, T., Igler, C., Sezgin, A., Henzinger, T. A., & Guet, C. C. (2021).
Long lived transients in gene regulation. Theoretical Computer Science.
Elsevier. https://doi.org/10.1016/j.tcs.2021.05.023
chicago: Petrov, Tatjana, Claudia Igler, Ali Sezgin, Thomas A Henzinger, and Calin
C Guet. “Long Lived Transients in Gene Regulation.” Theoretical Computer Science.
Elsevier, 2021. https://doi.org/10.1016/j.tcs.2021.05.023.
ieee: T. Petrov, C. Igler, A. Sezgin, T. A. Henzinger, and C. C. Guet, “Long lived
transients in gene regulation,” Theoretical Computer Science, vol. 893.
Elsevier, pp. 1–16, 2021.
ista: Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. 2021. Long lived transients
in gene regulation. Theoretical Computer Science. 893, 1–16.
mla: Petrov, Tatjana, et al. “Long Lived Transients in Gene Regulation.” Theoretical
Computer Science, vol. 893, Elsevier, 2021, pp. 1–16, doi:10.1016/j.tcs.2021.05.023.
short: T. Petrov, C. Igler, A. Sezgin, T.A. Henzinger, C.C. Guet, Theoretical Computer
Science 893 (2021) 1–16.
corr_author: '1'
date_created: 2021-07-11T22:01:18Z
date_published: 2021-06-04T00:00:00Z
date_updated: 2025-04-15T06:25:56Z
day: '04'
ddc:
- '004'
department:
- _id: ToHe
- _id: CaGu
doi: 10.1016/j.tcs.2021.05.023
external_id:
isi:
- '000710180500002'
file:
- access_level: open_access
checksum: d3aef34cfb13e53bba4cf44d01680793
content_type: application/pdf
creator: dernst
date_created: 2022-05-12T12:13:27Z
date_updated: 2022-05-12T12:13:27Z
file_id: '11364'
file_name: 2021_TheoreticalComputerScience_Petrov.pdf
file_size: 2566504
relation: main_file
success: 1
file_date_updated: 2022-05-12T12:13:27Z
has_accepted_license: '1'
intvolume: ' 893'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 1-16
project:
- _id: 25F42A32-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z211
name: Formal methods for the design and analysis of complex systems
publication: Theoretical Computer Science
publication_identifier:
issn:
- 0304-3975
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Long lived transients in gene regulation
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 893
year: '2021'
...
---
_id: '9746'
abstract:
- lang: eng
text: Evolutionary adaptation is a major source of antibiotic resistance in bacterial
pathogens. Evolution-informed therapy aims to constrain resistance by accounting
for bacterial evolvability. Sequential treatments with antibiotics that target
different bacterial processes were previously shown to limit adaptation through
genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous
sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly
lead to cross-resistance. We here challenged this assumption by determining the
evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments
involving both heterogenous and homogeneous antibiotic sets. To our surprise,
we found that fast switching between only β-lactam antibiotics resulted in increased
extinction of bacterial populations. We demonstrate that extinction is favored
by low rates of spontaneous resistance emergence and low levels of spontaneous
cross-resistance among the antibiotics in sequence. The uncovered principles may
help to guide the optimized use of available antibiotics in highly potent, evolution-informed
treatment designs.
acknowledgement: We would like to thank Leif Tueffers and João Botelho for discussions
and suggestions as well as Kira Haas and Julia Bunk for technical support. We acknowledge
financial support from the German Science Foundation (grant SCHU 1415/12-2 to HS,
and funding under Germany’s Excellence Strategy EXC 2167–390884018 as well as the
Research Training Group 2501 TransEvo to HS and SN), the Max Planck Society (IMPRS
scholarship to AB; Max-Planck fellowship to HS), and the Leibniz Science Campus
Evolutionary Medicine of the Lung (EvoLUNG, to HS and SN). This work was further
supported by the German Science Foundation Research Infrastructure NGS_CC (project
407495230) as part of the Next Generation Sequencing Competence Network (project
423957469). NGS analyses were carried out at the Competence Centre for Genomic Analysis
Kiel (CCGA Kiel).
article_number: e68876
article_processing_charge: No
article_type: original
author:
- first_name: Aditi
full_name: Batra, Aditi
last_name: Batra
- first_name: Roderich
full_name: Römhild, Roderich
id: 68E56E44-62B0-11EA-B963-444F3DDC885E
last_name: Römhild
orcid: 0000-0001-9480-5261
- first_name: Emilie
full_name: Rousseau, Emilie
last_name: Rousseau
- first_name: Sören
full_name: Franzenburg, Sören
last_name: Franzenburg
- first_name: Stefan
full_name: Niemann, Stefan
last_name: Niemann
- first_name: Hinrich
full_name: Schulenburg, Hinrich
last_name: Schulenburg
citation:
ama: Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. High
potency of sequential therapy with only beta-lactam antibiotics. eLife.
2021;10. doi:10.7554/elife.68876
apa: Batra, A., Römhild, R., Rousseau, E., Franzenburg, S., Niemann, S., & Schulenburg,
H. (2021). High potency of sequential therapy with only beta-lactam antibiotics.
ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.68876
chicago: Batra, Aditi, Roderich Römhild, Emilie Rousseau, Sören Franzenburg, Stefan
Niemann, and Hinrich Schulenburg. “High Potency of Sequential Therapy with Only
Beta-Lactam Antibiotics.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.68876.
ieee: A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, and H. Schulenburg,
“High potency of sequential therapy with only beta-lactam antibiotics,” eLife,
vol. 10. eLife Sciences Publications, 2021.
ista: Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. 2021.
High potency of sequential therapy with only beta-lactam antibiotics. eLife. 10,
e68876.
mla: Batra, Aditi, et al. “High Potency of Sequential Therapy with Only Beta-Lactam
Antibiotics.” ELife, vol. 10, e68876, eLife Sciences Publications, 2021,
doi:10.7554/elife.68876.
short: A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, H. Schulenburg,
ELife 10 (2021).
date_created: 2021-07-28T13:36:57Z
date_published: 2021-07-28T00:00:00Z
date_updated: 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: '9822'
abstract:
- lang: eng
text: Attachment of adhesive molecules on cell culture surfaces to restrict cell
adhesion to defined areas and shapes has been vital for the progress of in vitro
research. In currently existing patterning methods, a combination of pattern properties
such as stability, precision, specificity, high-throughput outcome, and spatiotemporal
control is highly desirable but challenging to achieve. Here, we introduce a versatile
and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent
patterning step and a subsequent functionalization of the pattern via click chemistry.
This two-step process is feasible on arbitrary surfaces and allows for generation
of sustainable patterns and gradients. The method is validated in different biological
systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining
the growth and migration of cells to the designated areas. We then implement a
sequential photopatterning approach by adding a second switchable patterning step,
allowing for spatiotemporal control over two distinct surface patterns. As a proof
of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis.
Our results show that the spatiotemporal control provided by our “sequential photopatterning”
system is essential for mimicking dynamic biological processes and that our innovative
approach has great potential for further applications in cell science.
acknowledgement: We would like to thank Charlott Leu for the production of our chromium
wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh
Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim
Rädler for his valuable scientific guidance.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Themistoklis
full_name: Zisis, Themistoklis
last_name: Zisis
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Miriam
full_name: Balles, Miriam
last_name: Balles
- first_name: Maibritt
full_name: Kretschmer, Maibritt
last_name: Kretschmer
- first_name: Maria
full_name: Nemethova, Maria
id: 34E27F1C-F248-11E8-B48F-1D18A9856A87
last_name: Nemethova
- first_name: Remy P
full_name: Chait, Remy P
id: 3464AE84-F248-11E8-B48F-1D18A9856A87
last_name: Chait
orcid: 0000-0003-0876-3187
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Janina
full_name: Lange, Janina
last_name: Lange
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
- first_name: Stefan
full_name: Zahler, Stefan
last_name: Zahler
citation:
ama: Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for
studying cellular processes under spatiotemporal control. ACS Applied Materials
and Interfaces. 2021;13(30):35545–35560. doi:10.1021/acsami.1c09850
apa: Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R.
P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular
processes under spatiotemporal control. ACS Applied Materials and Interfaces.
American Chemical Society. https://doi.org/10.1021/acsami.1c09850
chicago: Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria
Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning
for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied
Materials and Interfaces. American Chemical Society, 2021. https://doi.org/10.1021/acsami.1c09850.
ieee: T. Zisis et al., “Sequential and switchable patterning for studying
cellular processes under spatiotemporal control,” ACS Applied Materials and
Interfaces, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021.
ista: Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild
R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning
for studying cellular processes under spatiotemporal control. ACS Applied Materials
and Interfaces. 13(30), 35545–35560.
mla: Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying
Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and
Interfaces, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560,
doi:10.1021/acsami.1c09850.
short: T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait,
R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials
and Interfaces 13 (2021) 35545–35560.
corr_author: '1'
date_created: 2021-08-08T22:01:28Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2025-07-10T12:02:02Z
day: '04'
ddc:
- '620'
- '570'
department:
- _id: MiSi
- _id: GaTk
- _id: Bio
- _id: CaGu
doi: 10.1021/acsami.1c09850
ec_funded: 1
external_id:
isi:
- '000683741400026'
pmid:
- '34283577'
file:
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creator: asandaue
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file_id: '9833'
file_name: 2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf
file_size: 7123293
relation: main_file
success: 1
file_date_updated: 2021-08-09T09:44:03Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
issue: '30'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 35545–35560
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
publication: ACS Applied Materials and Interfaces
publication_identifier:
eissn:
- 1944-8252
issn:
- 1944-8244
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Sequential and switchable patterning for studying cellular processes under
spatiotemporal control
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 13
year: '2021'
...
---
OA_place: publisher
_id: '10307'
abstract:
- lang: eng
text: Bacteria-host interactions represent a continuous trade-off between benefit
and risk. Thus, the host immune response is faced with a non-trivial problem –
accommodate beneficial commensals and remove harmful pathogens. This is especially
difficult as molecular patterns, such as lipopolysaccharide or specific surface
organelles such as pili, are conserved in both, commensal and pathogenic bacteria.
Type 1 pili, tightly regulated by phase variation, are considered an important
virulence factor of pathogenic bacteria as they facilitate invasion into host
cells. While invasion represents a de facto passive mechanism for pathogens to
escape the host immune response, we demonstrate a fundamental role of type 1 pili
as active modulators of the innate and adaptive immune response.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: PreCl
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
citation:
ama: Tomasek K. Pathogenic Escherichia coli hijack the host immune response. 2021.
doi:10.15479/at:ista:10307
apa: Tomasek, K. (2021). Pathogenic Escherichia coli hijack the host immune response.
Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:10307
chicago: Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.”
Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:10307.
ieee: K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,”
Institute of Science and Technology Austria, 2021.
ista: Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response.
Institute of Science and Technology Austria.
mla: Tomasek, Kathrin. Pathogenic Escherichia Coli Hijack the Host Immune Response.
Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:10307.
short: K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response,
Institute of Science and Technology Austria, 2021.
corr_author: '1'
date_created: 2021-11-18T15:05:06Z
date_published: 2021-11-18T00:00:00Z
date_updated: 2026-04-08T07:14:01Z
day: '18'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MiSi
- _id: CaGu
- _id: GradSch
doi: 10.15479/at:ista:10307
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date_created: 2021-11-18T15:07:46Z
date_updated: 2022-12-20T23:30:05Z
embargo_to: open_access
file_id: '10309'
file_name: ThesisTomasekKathrin.docx
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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: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2021'
...
---
_id: '10316'
abstract:
- lang: eng
text: A key attribute of persistent or recurring bacterial infections is the ability
of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express
type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and
establish persistent infections. However, the molecular mechanisms and strategies
by which bacteria actively circumvent the immune response of the host remain poorly
understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide
detection, on dendritic cells as a previously undescribed binding partner of FimH,
the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH
amino acids involved in CD14 binding are highly conserved across pathogenic and
non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced
dendritic cell migration and blunted expression of co-stimulatory molecules, both
rate-limiting factors of T cell activation. While defining an active molecular
mechanism of immune evasion by pathogens, the interaction between FimH and CD14
represents a potential target to interfere with persistent and recurrent infections,
such as urinary tract infections or Crohn’s disease.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra
and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments
and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis.
We thank the IST Austria Scientific Service Units, especially the Bioimaging facility,
the Preclinical facility and the Electron microscopy facility for technical support,
Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions
and Daria Siekhaus for critically reading the manuscript. This work was supported
by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G.,
the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911)
to M.S.
article_processing_charge: No
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Ivana
full_name: Glatzová, Ivana
id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d
last_name: Glatzová
- first_name: Michael S.
full_name: Lukesch, Michael S.
last_name: Lukesch
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
citation:
ama: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
bioRxiv. doi:10.1101/2021.10.18.464770
apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &
Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the
host immune response by binding to CD14. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2021.10.18.464770
chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch,
Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli
Hijack the Host Immune Response by Binding to CD14.” BioRxiv. Cold Spring
Harbor Laboratory, n.d. https://doi.org/10.1101/2021.10.18.464770.
ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M.
K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune
response by binding to CD14,” bioRxiv. Cold Spring Harbor Laboratory.
ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
bioRxiv, 10.1101/2021.10.18.464770.
mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack
the Host Immune Response by Binding to CD14.” BioRxiv, Cold Spring Harbor
Laboratory, doi:10.1101/2021.10.18.464770.
short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt,
BioRxiv (n.d.).
corr_author: '1'
date_created: 2021-11-19T12:24:16Z
date_published: 2021-10-18T00:00:00Z
date_updated: 2026-06-05T22:33:36Z
day: '18'
department:
- _id: CaGu
- _id: MiSi
doi: 10.1101/2021.10.18.464770
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1
month: '10'
oa: 1
oa_version: Preprint
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
publication: bioRxiv
publication_status: draft
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '11843'
relation: later_version
status: public
- id: '10307'
relation: dissertation_contains
status: public
status: public
title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response
by binding to CD14
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2021'
...
---
_id: '8951'
abstract:
- lang: eng
text: Gene expression levels are influenced by multiple coexisting molecular mechanisms.
Some of these interactions, such as those of transcription factors and promoters
have been studied extensively. However, predicting phenotypes of gene regulatory
networks remains a major challenge. Here, we use a well-defined synthetic gene
regulatory network to study how network phenotypes depend on local genetic context,
i.e. the genetic neighborhood of a transcription factor and its relative position.
We show that one gene regulatory network with fixed topology can display not only
quantitatively but also qualitatively different phenotypes, depending solely on
the local genetic context of its components. Our results demonstrate that changes
in local genetic context can place a single transcriptional unit within two separate
regulons without the need for complex regulatory sequences. We propose that relative
order of individual transcriptional units, with its potential for combinatorial
complexity, plays an important role in shaping phenotypes of gene regulatory networks.
article_processing_charge: No
author:
- first_name: Anna A
full_name: Nagy-Staron, Anna A
id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
last_name: Nagy-Staron
orcid: 0000-0002-1391-8377
citation:
ama: Nagy-Staron AA. Sequences of gene regulatory network permutations for the article
“Local genetic context shapes the function of a gene regulatory network.” 2020.
doi:10.15479/AT:ISTA:8951
apa: Nagy-Staron, A. A. (2020). Sequences of gene regulatory network permutations
for the article “Local genetic context shapes the function of a gene regulatory
network.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8951
chicago: Nagy-Staron, Anna A. “Sequences of Gene Regulatory Network Permutations
for the Article ‘Local Genetic Context Shapes the Function of a Gene Regulatory
Network.’” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8951.
ieee: A. A. Nagy-Staron, “Sequences of gene regulatory network permutations for
the article ‘Local genetic context shapes the function of a gene regulatory network.’”
Institute of Science and Technology Austria, 2020.
ista: Nagy-Staron AA. 2020. Sequences of gene regulatory network permutations for
the article ‘Local genetic context shapes the function of a gene regulatory network’,
Institute of Science and Technology Austria, 10.15479/AT:ISTA:8951.
mla: Nagy-Staron, Anna A. Sequences of Gene Regulatory Network Permutations for
the Article “Local Genetic Context Shapes the Function of a Gene Regulatory Network.”
Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8951.
short: A.A. Nagy-Staron, (2020).
contributor:
- contributor_type: project_member
first_name: Anna A
id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
last_name: Nagy-Staron
- contributor_type: project_member
first_name: Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
- contributor_type: project_member
first_name: Caroline
last_name: Caruso Carter
- contributor_type: project_member
first_name: Elisabeth
last_name: Sonnleitner
- contributor_type: project_member
first_name: Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- contributor_type: project_member
first_name: Tiago
last_name: Paixão
- contributor_type: project_manager
first_name: Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
corr_author: '1'
date_created: 2020-12-20T10:00:26Z
date_published: 2020-12-21T00:00:00Z
date_updated: 2025-06-12T06:36:16Z
day: '21'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:8951
file:
- 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
- access_level: open_access
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
corr_author: '1'
date_created: 2020-01-28T10:41:49Z
date_published: 2020-01-28T00:00:00Z
date_updated: 2025-06-12T07:34:12Z
day: '28'
department:
- _id: CaGu
- _id: GaTk
doi: 10.15479/AT:ISTA:7383
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date_created: 2020-01-28T10:39:40Z
date_updated: 2020-07-14T12:47:57Z
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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: '7569'
abstract:
- lang: eng
text: 'Genes differ in the frequency at which they are expressed and in the form
of regulation used to control their activity. In particular, positive or negative
regulation can lead to activation of a gene in response to an external signal.
Previous works proposed that the form of regulation of a gene correlates with
its frequency of usage: positive regulation when the gene is frequently expressed
and negative regulation when infrequently expressed. Such network design means
that, in the absence of their regulators, the genes are found in their least required
activity state, hence regulatory intervention is often necessary. Due to the multitude
of genes and regulators, spurious binding and unbinding events, called “crosstalk”,
could occur. To determine how the form of regulation affects the global crosstalk
in the network, we used a mathematical model that includes multiple regulators
and multiple target genes. We found that crosstalk depends non-monotonically on
the availability of regulators. Our analysis showed that excess use of regulation
entailed by the formerly suggested network design caused high crosstalk levels
in a large part of the parameter space. We therefore considered the opposite ‘idle’
design, where the default unregulated state of genes is their frequently required
activity state. We found, that ‘idle’ design minimized the use of regulation and
thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae
using transcription factors binding data. We demonstrated that even partial network
data could suffice to estimate its global crosstalk, suggesting its applicability
to additional organisms. We found that S. cerevisiae estimated crosstalk is lower
than that of a random network, suggesting that natural selection reduces crosstalk.
In summary, our study highlights a new type of protein production cost which is
typically overlooked: that of regulatory interference caused by the presence of
excess regulators in the cell. It demonstrates the importance of whole-network
descriptions, which could show effects missed by single-gene models.'
article_number: e1007642
article_processing_charge: No
article_type: original
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Tamar
full_name: Friedlander, Tamar
last_name: Friedlander
citation:
ama: Grah R, Friedlander T. The relation between crosstalk and gene regulation form
revisited. PLOS Computational Biology. 2020;16(2). doi:10.1371/journal.pcbi.1007642
apa: Grah, R., & Friedlander, T. (2020). The relation between crosstalk and
gene regulation form revisited. PLOS Computational Biology. Public Library
of Science. https://doi.org/10.1371/journal.pcbi.1007642
chicago: Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene
Regulation Form Revisited.” PLOS Computational Biology. Public Library
of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.
ieee: R. Grah and T. Friedlander, “The relation between crosstalk and gene regulation
form revisited,” PLOS Computational Biology, vol. 16, no. 2. Public Library
of Science, 2020.
ista: Grah R, Friedlander T. 2020. The relation between crosstalk and gene regulation
form revisited. PLOS Computational Biology. 16(2), e1007642.
mla: Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene
Regulation Form Revisited.” PLOS Computational Biology, vol. 16, no. 2,
e1007642, Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642.
short: R. Grah, T. Friedlander, PLOS Computational Biology 16 (2020).
date_created: 2020-03-06T07:39:38Z
date_published: 2020-02-25T00:00:00Z
date_updated: 2026-04-08T07:25:08Z
day: '25'
ddc:
- '000'
- '570'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642
external_id:
isi:
- '000526725200019'
pmid:
- '32097416'
file:
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checksum: 5239dd134dc6e1c71fe7b3ce2953da37
content_type: application/pdf
creator: dernst
date_created: 2020-03-09T15:12:21Z
date_updated: 2020-07-14T12:48:00Z
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file_name: 2020_PlosCompBio_Grah.pdf
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intvolume: ' 16'
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language:
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month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: PLOS Computational Biology
publication_identifier:
issn:
- 1553-7358
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
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status: deleted
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status: public
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scopus_import: '1'
status: public
title: The relation between crosstalk and gene regulation form revisited
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2020'
...