---
_id: '8250'
abstract:
- lang: eng
text: 'Antibiotics that interfere with translation, when combined, interact in diverse
and difficult-to-predict ways. Here, we explain these interactions by “translation
bottlenecks”: points in the translation cycle where antibiotics block ribosomal
progression. To elucidate the underlying mechanisms of drug interactions between
translation inhibitors, we generate translation bottlenecks genetically using
inducible control of translation factors that regulate well-defined translation
cycle steps. These perturbations accurately mimic antibiotic action and drug interactions,
supporting that the interplay of different translation bottlenecks causes these
interactions. We further show that growth laws, combined with drug uptake and
binding kinetics, enable the direct prediction of a large fraction of observed
interactions, yet fail to predict suppression. However, varying two translation
bottlenecks simultaneously supports that dense traffic of ribosomes and competition
for translation factors account for the previously unexplained suppression. These
results highlight the importance of “continuous epistasis” in bacterial physiology.'
acknowledgement: "We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K.
Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive
comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support,
which rendered this\r\nwork possible. B.K. thanks all members of Guet group for
many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges
the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work.
We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A.
Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This
work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P
27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to
T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.),
and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310
(to T.B.). Open access funding provided by\r\nProjekt DEAL."
article_number: '4013'
article_processing_charge: No
article_type: original
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between
translation-inhibiting antibiotics. Nature Communications. 2020;11. doi:10.1038/s41467-020-17734-z
apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). Mechanisms of drug
interactions between translation-inhibiting antibiotics. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-020-17734-z
chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of
Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications.
Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17734-z.
ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions
between translation-inhibiting antibiotics,” Nature Communications, vol.
11. Springer Nature, 2020.
ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between
translation-inhibiting antibiotics. Nature Communications. 11, 4013.
mla: Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting
Antibiotics.” Nature Communications, vol. 11, 4013, Springer Nature, 2020,
doi:10.1038/s41467-020-17734-z.
short: B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020).
date_created: 2020-08-12T09:13:50Z
date_published: 2020-08-11T00:00:00Z
date_updated: 2026-04-26T22:30:41Z
day: '11'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1038/s41467-020-17734-z
external_id:
isi:
- '000562769300008'
pmid:
- '32782250'
file:
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checksum: 986bebb308850a55850028d3d2b5b664
content_type: application/pdf
creator: dernst
date_created: 2020-08-17T07:36:57Z
date_updated: 2020-08-17T07:36:57Z
file_id: '8275'
file_name: 2020_NatureComm_Kavcic.pdf
file_size: 1965672
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success: 1
file_date_updated: 2020-08-17T07:36:57Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
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month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
record:
- id: '8657'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Mechanisms of drug interactions between translation-inhibiting antibiotics
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 11
year: '2020'
...
---
_id: '9750'
abstract:
- lang: eng
text: Tension of the actomyosin cell cortex plays a key role in determining cell-cell
contact growth and size. The level of cortical tension outside of the cell-cell
contact, when pulling at the contact edge, scales with the total size to which
a cell-cell contact can grow1,2. Here we show in zebrafish primary germ layer
progenitor cells that this monotonic relationship only applies to a narrow range
of cortical tension increase, and that above a critical threshold, contact size
inversely scales with cortical tension. This switch from cortical tension increasing
to decreasing progenitor cell-cell contact size is caused by cortical tension
promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing
clustering and stability of E-cadherin at the contact. Once tension-mediated E-cadherin
stabilization at the contact exceeds a critical threshold level, the rate by which
the contact expands in response to pulling forces from the cortex sharply drops,
leading to smaller contacts at physiologically relevant timescales of contact
formation. Thus, the activity of cortical tension in expanding cell-cell contact
size is limited by tension stabilizing E-cadherin-actin complexes at the contact.
acknowledged_ssus:
- _id: Bio
- _id: EM-Fac
- _id: SSU
acknowledgement: We would like to thank Edouard Hannezo for discussions, Shayan Shami
Pour and Daniel Capek for help with data analysis, Vanessa Barone and other members
of the Heisenberg laboratory for thoughtful discussions and comments on the manuscript.
We also thank Jack Merrin for preparing the microwells, and the Scientific Service
Units at IST Austria, specifically Bioimaging and Electron Microscopy, and the Zebrafish
Facility for continuous support. We acknowledge Hitoshi Morita for the kind gift
of VinculinB-GFP plasmid. This research was supported by an ERC Advanced Grant (MECSPEC)
to C.-P.H, EMBO Long Term grant (ALTF 187-2013) to M.S and IST Fellow Marie-Curie
COFUND No. P_IST_EU01 to J.S.
article_processing_charge: No
author:
- first_name: Jana
full_name: Slovakova, Jana
id: 30F3F2F0-F248-11E8-B48F-1D18A9856A87
last_name: Slovakova
- first_name: Mateusz K
full_name: Sikora, Mateusz K
id: 2F74BCDE-F248-11E8-B48F-1D18A9856A87
last_name: Sikora
- first_name: Silvia
full_name: Caballero Mancebo, Silvia
id: 2F1E1758-F248-11E8-B48F-1D18A9856A87
last_name: Caballero Mancebo
orcid: 0000-0002-5223-3346
- first_name: Gabriel
full_name: Krens, Gabriel
id: 2B819732-F248-11E8-B48F-1D18A9856A87
last_name: Krens
orcid: 0000-0003-4761-5996
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Karla
full_name: Huljev, Karla
id: 44C6F6A6-F248-11E8-B48F-1D18A9856A87
last_name: Huljev
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
citation:
ama: Slovakova J, Sikora MK, Caballero Mancebo S, et al. Tension-dependent stabilization
of E-cadherin limits cell-cell contact expansion. bioRxiv. 2020. doi:10.1101/2020.11.20.391284
apa: Slovakova, J., Sikora, M. K., Caballero Mancebo, S., Krens, G., Kaufmann, W.,
Huljev, K., & Heisenberg, C.-P. J. (2020). Tension-dependent stabilization
of E-cadherin limits cell-cell contact expansion. bioRxiv. Cold Spring
Harbor Laboratory. https://doi.org/10.1101/2020.11.20.391284
chicago: Slovakova, Jana, Mateusz K Sikora, Silvia Caballero Mancebo, Gabriel Krens,
Walter Kaufmann, Karla Huljev, and Carl-Philipp J Heisenberg. “Tension-Dependent
Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion.” BioRxiv.
Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.11.20.391284.
ieee: J. Slovakova et al., “Tension-dependent stabilization of E-cadherin
limits cell-cell contact expansion,” bioRxiv. Cold Spring Harbor Laboratory,
2020.
ista: Slovakova J, Sikora MK, Caballero Mancebo S, Krens G, Kaufmann W, Huljev K,
Heisenberg C-PJ. 2020. Tension-dependent stabilization of E-cadherin limits cell-cell
contact expansion. bioRxiv, 10.1101/2020.11.20.391284.
mla: Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits
Cell-Cell Contact Expansion.” BioRxiv, Cold Spring Harbor Laboratory, 2020,
doi:10.1101/2020.11.20.391284.
short: J. Slovakova, M.K. Sikora, S. Caballero Mancebo, G. Krens, W. Kaufmann, K.
Huljev, C.-P.J. Heisenberg, BioRxiv (2020).
date_created: 2021-07-29T11:29:50Z
date_published: 2020-11-20T00:00:00Z
date_updated: 2026-04-26T22:30:43Z
day: '20'
department:
- _id: CaHe
- _id: EM-Fac
- _id: Bio
doi: 10.1101/2020.11.20.391284
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.11.20.391284
month: '11'
oa: 1
oa_version: Preprint
page: '41'
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 260F1432-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742573'
name: Interaction and feedback between cell mechanics and fate specification in
vertebrate gastrulation
- _id: 2521E28E-B435-11E9-9278-68D0E5697425
grant_number: 187-2013
name: Modulation of adhesion function in cell-cell contact formation by cortical
tension
publication: bioRxiv
publication_status: published
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '10766'
relation: later_version
status: public
- id: '9623'
relation: dissertation_contains
status: public
status: public
title: Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion
type: preprint
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2020'
...
---
_id: '7673'
abstract:
- lang: eng
text: Combining drugs can improve the efficacy of treatments. However, predicting
the effect of drug combinations is still challenging. The combined potency of
drugs determines the drug interaction, which is classified as synergistic, additive,
antagonistic, or suppressive. While probabilistic, non-mechanistic models exist,
there is currently no biophysical model that can predict antibiotic interactions.
Here, we present a physiologically relevant model of the combined action of antibiotics
that inhibit protein synthesis by targeting the ribosome. This model captures
the kinetics of antibiotic binding and transport, and uses bacterial growth laws
to predict growth in the presence of antibiotic combinations. We find that this
biophysical model can produce all drug interaction types except suppression. We
show analytically that antibiotics which cannot bind to the ribosome simultaneously
generally act as substitutes for one another, leading to additive drug interactions.
Previously proposed null expectations for higher-order drug interactions follow
as a limiting case of our model. We further extend the model to include the effects
of direct physical or allosteric interactions between individual drugs on the
ribosome. Notably, such direct interactions profoundly change the combined drug
effect, depending on the kinetic parameters of the drugs used. The model makes
additional predictions for the effects of resistance genes on drug interactions
and for interactions between ribosome-targeting antibiotics and antibiotics with
other targets. These findings enhance our understanding of the interplay between
drug action and cell physiology and are a key step toward a general framework
for predicting drug interactions.
article_processing_charge: No
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined
antibiotic action. bioRxiv. 2020. doi:10.1101/2020.04.18.047886
apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). A minimal biophysical
model of combined antibiotic action. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2020.04.18.047886
chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical
Model of Combined Antibiotic Action.” BioRxiv. Cold Spring Harbor Laboratory,
2020. https://doi.org/10.1101/2020.04.18.047886.
ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “A minimal biophysical model of
combined antibiotic action,” bioRxiv. Cold Spring Harbor Laboratory, 2020.
ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined
antibiotic action. bioRxiv, 10.1101/2020.04.18.047886.
mla: Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.”
BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.18.047886.
short: B. Kavcic, G. Tkačik, M.T. Bollenbach, BioRxiv (2020).
date_created: 2020-04-22T08:27:56Z
date_published: 2020-04-18T00:00:00Z
date_updated: 2026-04-26T22:30:41Z
day: '18'
department:
- _id: GaTk
doi: 10.1101/2020.04.18.047886
language:
- iso: eng
main_file_link:
- open_access: '1'
url: 'https://doi.org/10.1101/2020.04.18.047886 '
month: '04'
oa: 1
oa_version: Preprint
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: bioRxiv
publication_status: published
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '8997'
relation: later_version
status: public
- id: '8657'
relation: dissertation_contains
status: public
status: public
title: A minimal biophysical model of combined antibiotic action
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
OA_place: publisher
_id: '7258'
abstract:
- lang: eng
text: Many flows encountered in nature and applications are characterized by a chaotic
motion known as turbulence. Turbulent flows generate intense friction with pipe
walls and are responsible for considerable amounts of energy losses at world scale.
The nature of turbulent friction and techniques aimed at reducing it have been
subject of extensive research over the last century, but no definite answer has
been found yet. In this thesis we show that in pipes at moderate turbulent Reynolds
numbers friction is better described by the power law first introduced by Blasius
and not by the Prandtl–von Kármán formula. At higher Reynolds numbers, large scale
motions gradually become more important in the flow and can be related to the
change in scaling of friction. Next, we present a series of new techniques that
can relaminarize turbulence by suppressing a key mechanism that regenerates it
at walls, the lift–up effect. In addition, we investigate the process of turbulence
decay in several experiments and discuss the drag reduction potential. Finally,
we examine the behavior of friction under pulsating conditions inspired by the
human heart cycle and we show that under such circumstances turbulent friction
can be reduced to produce energy savings.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Davide
full_name: Scarselli, Davide
id: 40315C30-F248-11E8-B48F-1D18A9856A87
last_name: Scarselli
orcid: 0000-0001-5227-4271
citation:
ama: Scarselli D. New approaches to reduce friction in turbulent pipe flow. 2020.
doi:10.15479/AT:ISTA:7258
apa: Scarselli, D. (2020). New approaches to reduce friction in turbulent pipe
flow. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7258
chicago: Scarselli, Davide. “New Approaches to Reduce Friction in Turbulent Pipe
Flow.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7258.
ieee: D. Scarselli, “New approaches to reduce friction in turbulent pipe flow,”
Institute of Science and Technology Austria, 2020.
ista: Scarselli D. 2020. New approaches to reduce friction in turbulent pipe flow.
Institute of Science and Technology Austria.
mla: Scarselli, Davide. New Approaches to Reduce Friction in Turbulent Pipe Flow.
Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7258.
short: D. Scarselli, New Approaches to Reduce Friction in Turbulent Pipe Flow, Institute
of Science and Technology Austria, 2020.
corr_author: '1'
date_created: 2020-01-12T16:07:26Z
date_published: 2020-01-13T00:00:00Z
date_updated: 2026-04-08T07:28:22Z
day: '13'
ddc:
- '532'
degree_awarded: PhD
department:
- _id: BjHo
doi: 10.15479/AT:ISTA:7258
ec_funded: 1
file:
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checksum: 4df1ab24e9896635106adde5a54615bf
content_type: application/zip
creator: dscarsel
date_created: 2020-01-12T15:57:14Z
date_updated: 2021-01-13T23:30:05Z
embargo_to: open_access
file_id: '7259'
file_name: 2020_Scarselli_Thesis.zip
file_size: 26640830
relation: source_file
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checksum: 48659ab98e3414293c7a721385c2fd1c
content_type: application/pdf
creator: dscarsel
date_created: 2020-01-12T15:56:14Z
date_updated: 2021-01-13T23:30:05Z
embargo: 2021-01-12
file_id: '7260'
file_name: 2020_Scarselli_Thesis.pdf
file_size: 8515844
relation: main_file
file_date_updated: 2021-01-13T23:30:05Z
has_accepted_license: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: None
page: '174'
project:
- _id: 25152F3A-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '306589'
name: Decoding the complexity of turbulence at its origin
- _id: 25104D44-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '737549'
name: Eliminating turbulence in oil pipelines
- _id: 25136C54-B435-11E9-9278-68D0E5697425
grant_number: HO 4393/1-2
name: Experimental studies of the turbulence transition and transport processes
in turbulent Taylor-Couette currents
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '422'
relation: part_of_dissertation
status: public
- id: '461'
relation: part_of_dissertation
status: public
- id: '6228'
relation: part_of_dissertation
status: public
- id: '6486'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
title: New approaches to reduce friction in turbulent pipe flow
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2020'
...
---
_id: '7427'
abstract:
- lang: eng
text: Plants, like other multicellular organisms, survive through a delicate balance
between growth and defense against pathogens. Salicylic acid (SA) is a major defense
signal in plants, and the perception mechanism as well as downstream signaling
activating the immune response are known. Here, we identify a parallel SA signaling
that mediates growth attenuation. SA directly binds to A subunits of protein phosphatase
2A (PP2A), inhibiting activity of this complex. Among PP2A targets, the PIN2 auxin
transporter is hyperphosphorylated in response to SA, leading to changed activity
of this important growth regulator. Accordingly, auxin transport and auxin-mediated
root development, including growth, gravitropic response, and lateral root organogenesis,
are inhibited. This study reveals how SA, besides activating immunity, concomitantly
attenuates growth through crosstalk with the auxin distribution network. Further
analysis of this dual role of SA and characterization of additional SA-regulated
PP2A targets will provide further insights into mechanisms maintaining a balance
between growth and defense.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: "We thank Shigeyuki Betsuyaku (University of Tsukuba), Alison Delong
(Brown University), Xinnian Dong (Duke University), Dolf Weijers (Wageningen University),
Yuelin Zhang (UBC), and Martine Pastuglia (Institut Jean-Pierre Bourgin) for sharing
published materials; Jana Riederer for help with cantharidin physiological analysis;
David Domjan for help with cloning pET28a-PIN2HL; Qing Lu for help with DARTS; Hana
Kozubı´kova´ for technical support on SA derivative synthesis; Zuzana Vondra´ kova´
for technical support with tobacco cells; Lucia Strader (Washington University),
Bert De Rybel (Ghent University), Bartel Vanholme (Ghent University), and Lukas
Mach (BOKU) for helpful discussions; and bioimaging and life science facilities
of IST Austria for continuous support. We gratefully acknowledge the Nottingham
Arabidopsis Stock Center (NASC) for providing T-DNA insertional mutants. The DSC
and SPR instruments were provided by the EQ-BOKU VIBT GmbH and the BOKU Core Facility
for Biomolecular and Cellular Analysis, with help of Irene Schaffner. The research
leading to these results has received funding from the European Union’s Horizon
2020 program (ERC grant agreement no. 742985 to J.F.) and the People Programme (Marie
Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013)
under REA grant agreement no. 291734. S.T. was supported by a European Molecular
Biology Organization (EMBO) long-term postdoctoral fellowship (ALTF 723-2015). O.N.
was supported by the Ministry of Education, Youth and Sports of the Czech Republic
(European Regional Development Fund-Project ‘‘Centre for Experimental Plant Biology’’
no. CZ.02.1.01/0.0/0.0/16_019/0000738). J. Pospısil was supported by European Regional
Development Fund Project ‘‘Centre for Experimental Plant Biology’’\r\n(no. CZ.02.1.01/0.0/0.0/16_019/0000738).
J. Petrasek was supported by EU Operational Programme Prague-Competitiveness (no.
CZ.2.16/3.1.00/21519). "
article_processing_charge: No
article_type: original
author:
- first_name: Shutang
full_name: Tan, Shutang
id: 2DE75584-F248-11E8-B48F-1D18A9856A87
last_name: Tan
orcid: 0000-0002-0471-8285
- first_name: Melinda F
full_name: Abas, Melinda F
id: 3CFB3B1C-F248-11E8-B48F-1D18A9856A87
last_name: Abas
- first_name: Inge
full_name: Verstraeten, Inge
id: 362BF7FE-F248-11E8-B48F-1D18A9856A87
last_name: Verstraeten
orcid: 0000-0001-7241-2328
- first_name: Matous
full_name: Glanc, Matous
id: 1AE1EA24-02D0-11E9-9BAA-DAF4881429F2
last_name: Glanc
orcid: 0000-0003-0619-7783
- first_name: Gergely
full_name: Molnar, Gergely
id: 34F1AF46-F248-11E8-B48F-1D18A9856A87
last_name: Molnar
- first_name: Jakub
full_name: Hajny, Jakub
id: 4800CC20-F248-11E8-B48F-1D18A9856A87
last_name: Hajny
orcid: 0000-0003-2140-7195
- first_name: Pavel
full_name: Lasák, Pavel
last_name: Lasák
- first_name: Ivan
full_name: Petřík, Ivan
last_name: Petřík
- first_name: Eugenia
full_name: Russinova, Eugenia
last_name: Russinova
- first_name: Jan
full_name: Petrášek, Jan
last_name: Petrášek
- first_name: Ondřej
full_name: Novák, Ondřej
last_name: Novák
- first_name: Jiří
full_name: Pospíšil, Jiří
last_name: Pospíšil
- first_name: Jiří
full_name: Friml, Jiří
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
citation:
ama: Tan S, Abas MF, Verstraeten I, et al. Salicylic acid targets protein phosphatase
2A to attenuate growth in plants. Current Biology. 2020;30(3):381-395.e8.
doi:10.1016/j.cub.2019.11.058
apa: Tan, S., Abas, M. F., Verstraeten, I., Glanc, M., Molnar, G., Hajny, J., …
Friml, J. (2020). Salicylic acid targets protein phosphatase 2A to attenuate growth
in plants. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2019.11.058
chicago: Tan, Shutang, Melinda F Abas, Inge Verstraeten, Matous Glanc, Gergely Molnar,
Jakub Hajny, Pavel Lasák, et al. “Salicylic Acid Targets Protein Phosphatase 2A
to Attenuate Growth in Plants.” Current Biology. Cell Press, 2020. https://doi.org/10.1016/j.cub.2019.11.058.
ieee: S. Tan et al., “Salicylic acid targets protein phosphatase 2A to attenuate
growth in plants,” Current Biology, vol. 30, no. 3. Cell Press, p. 381–395.e8,
2020.
ista: Tan S, Abas MF, Verstraeten I, Glanc M, Molnar G, Hajny J, Lasák P, Petřík
I, Russinova E, Petrášek J, Novák O, Pospíšil J, Friml J. 2020. Salicylic acid
targets protein phosphatase 2A to attenuate growth in plants. Current Biology.
30(3), 381–395.e8.
mla: Tan, Shutang, et al. “Salicylic Acid Targets Protein Phosphatase 2A to Attenuate
Growth in Plants.” Current Biology, vol. 30, no. 3, Cell Press, 2020, p.
381–395.e8, doi:10.1016/j.cub.2019.11.058.
short: S. Tan, M.F. Abas, I. Verstraeten, M. Glanc, G. Molnar, J. Hajny, P. Lasák,
I. Petřík, E. Russinova, J. Petrášek, O. Novák, J. Pospíšil, J. Friml, Current
Biology 30 (2020) 381–395.e8.
corr_author: '1'
date_created: 2020-02-02T23:01:00Z
date_published: 2020-02-03T00:00:00Z
date_updated: 2026-04-26T22:30:45Z
day: '03'
ddc:
- '580'
department:
- _id: JiFr
- _id: EvBe
doi: 10.1016/j.cub.2019.11.058
ec_funded: 1
external_id:
isi:
- '000511287900018'
pmid:
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page: 381-395.e8
pmid: 1
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742985'
name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 256FEF10-B435-11E9-9278-68D0E5697425
grant_number: 723-2015
name: Molecular Mechanism underlying Salicylic Acid Regulation of Endocytic Trafficking
in Arabidopsis
publication: Current Biology
publication_identifier:
issn:
- '09609822'
publication_status: published
publisher: Cell Press
quality_controlled: '1'
related_material:
record:
- id: '8822'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Salicylic acid targets protein phosphatase 2A to attenuate growth in plants
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 30
year: '2020'
...
---
_id: '7500'
abstract:
- lang: eng
text: "Plant survival depends on vascular tissues, which originate in a self‐organizing
manner as strands of cells co‐directionally transporting the plant hormone auxin.
The latter phenomenon (also known as auxin canalization) is classically hypothesized
to be regulated by auxin itself via the effect of this hormone on the polarity
of its own intercellular transport. Correlative observations supported this concept,
but molecular insights remain limited.\r\nIn the current study, we established
an experimental system based on the model Arabidopsis thaliana, which exhibits
auxin transport channels and formation of vasculature strands in response to local
auxin application.\r\nOur methodology permits the genetic analysis of auxin canalization
under controllable experimental conditions. By utilizing this opportunity, we
confirmed the dependence of auxin canalization on a PIN‐dependent auxin transport
and nuclear, TIR1/AFB‐mediated auxin signaling. We also show that leaf venation
and auxin‐mediated PIN repolarization in the root require TIR1/AFB signaling.\r\nFurther
studies based on this experimental system are likely to yield better understanding
of the mechanisms underlying auxin transport polarization in other developmental
contexts."
acknowledgement: We thank Mark Estelle, José M. Alonso and the Arabidopsis Stock Centre
for providing seeds. We acknowledge the core facility CELLIM of CEITEC supported
by the MEYS CR (LM2015062 Czech‐BioImaging) and Plant Sciences Core Facility of
CEITEC Masaryk University for help in generating essential data. This project received
funding from the European Research Council (ERC) under the European Union's Horizon
2020 research and innovation program (grant agreement no. 742985) and the Czech
Science Foundation GAČR (GA13‐40637S and GA18‐26981S) to JF. JH is the recipient
of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Science
and Technology. The authors declare no competing interests.
article_processing_charge: No
article_type: original
author:
- first_name: E
full_name: Mazur, E
last_name: Mazur
- first_name: Ivan
full_name: Kulik, Ivan
id: F0AB3FCE-02D1-11E9-BD0E-99399A5D3DEB
last_name: Kulik
- first_name: Jakub
full_name: Hajny, Jakub
id: 4800CC20-F248-11E8-B48F-1D18A9856A87
last_name: Hajny
orcid: 0000-0003-2140-7195
- first_name: Jiří
full_name: Friml, Jiří
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
citation:
ama: Mazur E, Kulik I, Hajny J, Friml J. Auxin canalization and vascular tissue
formation by TIR1/AFB-mediated auxin signaling in arabidopsis. New Phytologist.
2020;226(5):1375-1383. doi:10.1111/nph.16446
apa: Mazur, E., Kulik, I., Hajny, J., & Friml, J. (2020). Auxin canalization
and vascular tissue formation by TIR1/AFB-mediated auxin signaling in arabidopsis.
New Phytologist. Wiley. https://doi.org/10.1111/nph.16446
chicago: Mazur, E, Ivan Kulik, Jakub Hajny, and Jiří Friml. “Auxin Canalization
and Vascular Tissue Formation by TIR1/AFB-Mediated Auxin Signaling in Arabidopsis.”
New Phytologist. Wiley, 2020. https://doi.org/10.1111/nph.16446.
ieee: E. Mazur, I. Kulik, J. Hajny, and J. Friml, “Auxin canalization and vascular
tissue formation by TIR1/AFB-mediated auxin signaling in arabidopsis,” New
Phytologist, vol. 226, no. 5. Wiley, pp. 1375–1383, 2020.
ista: Mazur E, Kulik I, Hajny J, Friml J. 2020. Auxin canalization and vascular
tissue formation by TIR1/AFB-mediated auxin signaling in arabidopsis. New Phytologist.
226(5), 1375–1383.
mla: Mazur, E., et al. “Auxin Canalization and Vascular Tissue Formation by TIR1/AFB-Mediated
Auxin Signaling in Arabidopsis.” New Phytologist, vol. 226, no. 5, Wiley,
2020, pp. 1375–83, doi:10.1111/nph.16446.
short: E. Mazur, I. Kulik, J. Hajny, J. Friml, New Phytologist 226 (2020) 1375–1383.
corr_author: '1'
date_created: 2020-02-18T10:03:47Z
date_published: 2020-06-01T00:00:00Z
date_updated: 2026-04-26T22:30:45Z
day: '01'
ddc:
- '580'
department:
- _id: JiFr
doi: 10.1111/nph.16446
ec_funded: 1
external_id:
isi:
- '000514939700001'
pmid:
- '31971254'
file:
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checksum: 17de728b0205979feb95ce663ba918c2
content_type: application/pdf
creator: dernst
date_created: 2020-11-20T09:32:10Z
date_updated: 2020-11-20T09:32:10Z
file_id: '8781'
file_name: 2020_NewPhytologist_Mazur.pdf
file_size: 2106888
relation: main_file
success: 1
file_date_updated: 2020-11-20T09:32:10Z
has_accepted_license: '1'
intvolume: ' 226'
isi: 1
issue: '5'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 1375-1383
pmid: 1
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742985'
name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 2699E3D2-B435-11E9-9278-68D0E5697425
grant_number: '25239'
name: Cell surface receptor complexes for PIN polarity and auxin-mediated development
publication: New Phytologist
publication_identifier:
eissn:
- 1469-8137
issn:
- 0028-646x
publication_status: published
publisher: Wiley
quality_controlled: '1'
related_material:
record:
- id: '8822'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Auxin canalization and vascular tissue formation by TIR1/AFB-mediated auxin
signaling in arabidopsis
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 226
year: '2020'
...
---
OA_place: publisher
_id: '8822'
abstract:
- lang: eng
text: "Self-organization is a hallmark of plant development manifested e.g. by intricate
leaf vein patterns, flexible formation of vasculature during organogenesis or
its regeneration following wounding. Spontaneously arising channels transporting
the phytohormone auxin, created by coordinated polar localizations of PIN-FORMED
1 (PIN1) auxin exporter, provide positional cues for these as well as other plant
patterning processes. To find regulators acting downstream of auxin and the TIR1/AFB
auxin signaling pathway essential for PIN1 coordinated polarization during auxin
canalization, we performed microarray experiments. Besides the known components
of general PIN polarity maintenance, such as PID and PIP5K kinases, we identified
and characterized a new regulator of auxin canalization, the transcription factor
WRKY DNA-BINDING PROTEIN 23 (WRKY23).\r\nNext, we designed a subsequent microarray
experiment to further uncover other molecular players, downstream of auxin-TIR1/AFB-WRKY23
involved in the regulation of auxin-mediated PIN repolarization. We identified
a novel and crucial part of the molecular machinery underlying auxin canalization.
The auxin-regulated malectin-type receptor-like kinase CAMEL and the associated
leucine-rich repeat receptor-like kinase CANAR target and directly phosphorylate
PIN auxin transporters. camel and canar mutants are impaired in PIN1 subcellular
trafficking and auxin-mediated repolarization leading to defects in auxin transport,
ultimately to leaf venation and vasculature regeneration defects. Our results
describe the CAMEL-CANAR receptor complex, which is required for auxin feed-back
on its own transport and thus for coordinated tissue polarization during auxin
canalization."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Jakub
full_name: Hajny, Jakub
id: 4800CC20-F248-11E8-B48F-1D18A9856A87
last_name: Hajny
orcid: 0000-0003-2140-7195
citation:
ama: Hajny J. Identification and characterization of the molecular machinery of
auxin-dependent canalization during vasculature formation and regeneration. 2020.
doi:10.15479/AT:ISTA:8822
apa: Hajny, J. (2020). Identification and characterization of the molecular machinery
of auxin-dependent canalization during vasculature formation and regeneration.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8822
chicago: Hajny, Jakub. “Identification and Characterization of the Molecular Machinery
of Auxin-Dependent Canalization during Vasculature Formation and Regeneration.”
Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8822.
ieee: J. Hajny, “Identification and characterization of the molecular machinery
of auxin-dependent canalization during vasculature formation and regeneration,”
Institute of Science and Technology Austria, 2020.
ista: Hajny J. 2020. Identification and characterization of the molecular machinery
of auxin-dependent canalization during vasculature formation and regeneration.
Institute of Science and Technology Austria.
mla: Hajny, Jakub. Identification and Characterization of the Molecular Machinery
of Auxin-Dependent Canalization during Vasculature Formation and Regeneration.
Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8822.
short: J. Hajny, Identification and Characterization of the Molecular Machinery
of Auxin-Dependent Canalization during Vasculature Formation and Regeneration,
Institute of Science and Technology Austria, 2020.
corr_author: '1'
date_created: 2020-12-01T12:38:18Z
date_published: 2020-12-01T00:00:00Z
date_updated: 2026-04-08T07:28:35Z
day: '01'
ddc:
- '580'
degree_awarded: PhD
department:
- _id: JiFr
doi: 10.15479/AT:ISTA:8822
file:
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content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: jhajny
date_created: 2020-12-04T07:27:52Z
date_updated: 2021-07-16T22:30:03Z
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file_id: '8919'
file_name: Jakub Hajný IST Austria final_JH.docx
file_size: 91279806
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date_created: 2020-12-09T15:04:41Z
date_updated: 2021-12-08T23:30:03Z
embargo: 2021-12-07
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file_size: 68707697
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has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: '249'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '449'
relation: part_of_dissertation
status: public
- id: '7500'
relation: part_of_dissertation
status: public
- id: '6260'
relation: part_of_dissertation
status: public
- id: '7427'
relation: part_of_dissertation
status: public
- id: '191'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Jiří
full_name: Friml, Jiří
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
title: Identification and characterization of the molecular machinery of auxin-dependent
canalization during vasculature formation and regeneration
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2020'
...
---
OA_place: publisher
_id: '8983'
abstract:
- lang: eng
text: Metabolic adaptation is a critical feature of migrating cells. It tunes the
metabolic programs of migrating cells to allow them to efficiently exert their
crucial roles in development, inflammatory responses and tumor metastasis. Cell
migration through physically challenging contexts requires energy. However, how
the metabolic reprogramming that underlies in vivo cell invasion is controlled
is still unanswered. In my PhD project, I identify a novel conserved metabolic
shift in Drosophila melanogaster immune cells that by modulating their bioenergetic
potential controls developmentally programmed tissue invasion. We show that this
regulation requires a novel conserved nuclear protein, named Atossa. Atossa enhances
the transcription of a set of proteins, including an RNA helicase Porthos and
two metabolic enzymes, each of which increases the tissue invasion of leading
Drosophila macrophages and can rescue the atossa mutant phenotype. Porthos selectively
regulates the translational efficiency of a subset of mRNAs containing a 5’-UTR
cis-regulatory TOP-like sequence. These 5’TOPL mRNA targets encode mitochondrial-related
proteins, including subunits of mitochondrial oxidative phosphorylation (OXPHOS)
components III and V and other metabolic-related proteins. Porthos powers up mitochondrial
OXPHOS to engender a sufficient ATP supply, which is required for tissue invasion
of leading macrophages. Atossa’s two vertebrate orthologs rescue the invasion
defect. In my PhD project, I elucidate that Atossa displays a conserved developmental
metabolic control to modulate metabolic capacities and the cellular energy state,
through altered transcription and translation, to aid the tissue infiltration
of leading cells into energy demanding barriers.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: E-Lib
- _id: CampIT
acknowledgement: Also, I would like to express my appreciation and thanks to the Bioimaging
facility, LSF, GSO, library, and IT people at IST Austria.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Shamsi
full_name: Emtenani, Shamsi
id: 49D32318-F248-11E8-B48F-1D18A9856A87
last_name: Emtenani
orcid: 0000-0001-6981-6938
citation:
ama: Emtenani S. Metabolic regulation of Drosophila macrophage tissue invasion.
2020. doi:10.15479/AT:ISTA:8983
apa: Emtenani, S. (2020). Metabolic regulation of Drosophila macrophage tissue
invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8983
chicago: Emtenani, Shamsi. “Metabolic Regulation of Drosophila Macrophage Tissue
Invasion.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8983.
ieee: S. Emtenani, “Metabolic regulation of Drosophila macrophage tissue invasion,”
Institute of Science and Technology Austria, 2020.
ista: Emtenani S. 2020. Metabolic regulation of Drosophila macrophage tissue invasion.
Institute of Science and Technology Austria.
mla: Emtenani, Shamsi. Metabolic Regulation of Drosophila Macrophage Tissue Invasion.
Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8983.
short: S. Emtenani, Metabolic Regulation of Drosophila Macrophage Tissue Invasion,
Institute of Science and Technology Austria, 2020.
corr_author: '1'
date_created: 2020-12-30T15:41:26Z
date_published: 2020-12-30T00:00:00Z
date_updated: 2026-04-08T07:28:54Z
day: '30'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: DaSi
doi: 10.15479/AT:ISTA:8983
file:
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checksum: ec2797ab7a6f253b35df0572b36d1b43
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creator: semtenan
date_created: 2020-12-30T15:34:01Z
date_updated: 2021-12-31T23:30:04Z
embargo: 2021-12-30
file_id: '8984'
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file_size: 10848175
relation: main_file
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checksum: cc30e6608a9815414024cf548dff3b3a
content_type: application/pdf
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date_updated: 2021-12-31T23:30:04Z
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file_id: '8985'
file_name: Thesis_Shamsi_Emtenani_source file.pdf
file_size: 10073648
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file_date_updated: 2021-12-31T23:30:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: '141'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '8557'
relation: part_of_dissertation
status: public
- id: '6187'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Daria E
full_name: Siekhaus, Daria E
id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
last_name: Siekhaus
orcid: 0000-0001-8323-8353
title: Metabolic regulation of Drosophila macrophage tissue invasion
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2020'
...
---
_id: '8557'
abstract:
- lang: eng
text: The infiltration of immune cells into tissues underlies the establishment
of tissue resident macrophages, and responses to infections and tumors. Yet the
mechanisms immune cells utilize to negotiate tissue barriers in living organisms
are not well understood, and a role for cortical actin has not been examined.
Here we find that the tissue invasion of Drosophila macrophages, also known as
plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated
by the Drosophila member of the fos proto oncogene transcription factor family
(Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances
F-actin levels around the entire macrophage surface by increasing mRNA levels
of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking
filamin Cheerio which are themselves required for invasion. Cortical F-actin levels
are critical as expressing a dominant active form of Diaphanous, a actin polymerizing
Formin, can rescue the Dfos Dominant Negative macrophage invasion defect. In vivo
imaging shows that Dfos is required to enhance the efficiency of the initial phases
of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program
in macrophages counteracts the constraint produced by the tension of surrounding
tissues and buffers the mechanical properties of the macrophage nucleus from affecting
tissue entry. We thus identify tuning the cortical actin cytoskeleton through
Dfos as a key process allowing efficient forward movement of an immune cell into
surrounding tissues.
acknowledged_ssus:
- _id: LifeSc
acknowledgement: 'We thank the following for their contributions: The Drosophila Genomics
Resource Center supported by NIH grant 2P40OD010949-10A1 for plasmids, K. Brueckner.
B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington Drosophila Stock Center
supported by NIH grant P40OD018537 and the Vienna Drosophila Resource Center for
fly stocks, FlyBase (Thurmond et al., 2019) for essential genomic information, and
the BDGP in situ database for data (Tomancak et al., 2002, 2007). For antibodies,
we thank the Developmental Studies Hybridoma Bank, which was created by the Eunice
Kennedy Shriver National Institute of Child Health and Human Development of the
NIH, and is maintained at the University of Iowa, as well as J. Zeitlinger for her
generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities for
RNA sequencing and analysis and the Life Scientific Service Units at IST Austria
for technical support and assistance with microscopy and FACS analysis. We thank
C.P. Heisenberg, P. Martin, M. Sixt and Siekhaus group members for discussions and
T.Hurd, A. Ratheesh and P. Rangan for comments on the manuscript. A.G. was supported
by the Austrian Science Fund (FWF) grant DASI_FWF01_P29638S, D.E.S. by Marie Curie
CIG 334077/IRTIM. M.S. is supported by the FWF, PhD program W1212 915 and the European
Research Council (ERC) Advanced grant (ERC-2015-AdG TNT-Tumors 694883). S.W. is
supported by an OEAW, DOC fellowship.'
article_processing_charge: No
author:
- first_name: Vera
full_name: Belyaeva, Vera
id: 47F080FE-F248-11E8-B48F-1D18A9856A87
last_name: Belyaeva
- first_name: Stephanie
full_name: Wachner, Stephanie
id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87
last_name: Wachner
- first_name: Igor
full_name: Gridchyn, Igor
id: 4B60654C-F248-11E8-B48F-1D18A9856A87
last_name: Gridchyn
orcid: 0000-0002-1807-1929
- first_name: Markus
full_name: Linder, Markus
last_name: Linder
- first_name: Shamsi
full_name: Emtenani, Shamsi
id: 49D32318-F248-11E8-B48F-1D18A9856A87
last_name: Emtenani
orcid: 0000-0001-6981-6938
- first_name: Attila
full_name: György, Attila
id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
last_name: György
orcid: 0000-0002-1819-198X
- first_name: Maria
full_name: Sibilia, Maria
last_name: Sibilia
- first_name: Daria E
full_name: Siekhaus, Daria E
id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
last_name: Siekhaus
orcid: 0000-0001-8323-8353
citation:
ama: Belyaeva V, Wachner S, Gridchyn I, et al. Cortical actin properties controlled
by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance.
bioRxiv. doi:10.1101/2020.09.18.301481
apa: Belyaeva, V., Wachner, S., Gridchyn, I., Linder, M., Emtenani, S., György,
A., … Siekhaus, D. E. (n.d.). Cortical actin properties controlled by Drosophila
Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv.
https://doi.org/10.1101/2020.09.18.301481
chicago: Belyaeva, Vera, Stephanie Wachner, Igor Gridchyn, Markus Linder, Shamsi
Emtenani, Attila György, Maria Sibilia, and Daria E Siekhaus. “Cortical Actin
Properties Controlled by Drosophila Fos Aid Macrophage Infiltration against Surrounding
Tissue Resistance.” BioRxiv, n.d. https://doi.org/10.1101/2020.09.18.301481.
ieee: V. Belyaeva et al., “Cortical actin properties controlled by Drosophila
Fos aid macrophage infiltration against surrounding tissue resistance,” bioRxiv.
.
ista: Belyaeva V, Wachner S, Gridchyn I, Linder M, Emtenani S, György A, Sibilia
M, Siekhaus DE. Cortical actin properties controlled by Drosophila Fos aid macrophage
infiltration against surrounding tissue resistance. bioRxiv, 10.1101/2020.09.18.301481.
mla: Belyaeva, Vera, et al. “Cortical Actin Properties Controlled by Drosophila
Fos Aid Macrophage Infiltration against Surrounding Tissue Resistance.” BioRxiv,
doi:10.1101/2020.09.18.301481.
short: V. Belyaeva, S. Wachner, I. Gridchyn, M. Linder, S. Emtenani, A. György,
M. Sibilia, D.E. Siekhaus, BioRxiv (n.d.).
corr_author: '1'
date_created: 2020-09-23T09:36:47Z
date_published: 2020-09-18T00:00:00Z
date_updated: 2026-04-26T22:30:46Z
day: '18'
department:
- _id: DaSi
- _id: JoCs
doi: 10.1101/2020.09.18.301481
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.09.18.301481
month: '09'
oa: 1
oa_version: Preprint
project:
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29638
name: The role of Drosophila TNF alpha in immune cell invasion
- _id: 2536F660-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '334077'
name: Investigating the role of transporters in invasive migration through junctions
- _id: 26199CA4-B435-11E9-9278-68D0E5697425
grant_number: '24800'
name: Implications of a TGFβ/Dpp-activated subpopulation for Drosophila macrophage
migration
publication: bioRxiv
publication_status: draft
related_material:
record:
- id: '10614'
relation: later_version
status: public
- id: '8983'
relation: dissertation_contains
status: public
status: public
title: Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration
against surrounding tissue resistance
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
OA_place: publisher
_id: '8340'
abstract:
- lang: eng
text: Mitochondria are sites of oxidative phosphorylation in eukaryotic cells. Oxidative
phosphorylation operates by a chemiosmotic mechanism made possible by redox-driven
proton pumping machines which establish a proton motive force across the inner
mitochondrial membrane. This electrochemical proton gradient is used to drive
ATP synthesis, which powers the majority of cellular processes such as protein
synthesis, locomotion and signalling. In this thesis I investigate the structures
and molecular mechanisms of two inner mitochondrial proton pumping enzymes, respiratory
complex I and transhydrogenase. I present the first high-resolution structure
of the full transhydrogenase from any species, and a significantly improved structure
of complex I. Improving the resolution from 3.3 Å available previously to up to
2.3 Å in this thesis allowed us to model bound water molecules, crucial in the
proton pumping mechanism. For both enzymes, up to five cryo-EM datasets with different
substrates and inhibitors bound were solved to delineate the catalytic cycle and
understand the proton pumping mechanism. In transhydrogenase, the proton channel
is gated by reversible detachment of the NADP(H)-binding domain which opens the
proton channel to the opposite sites of the membrane. In complex I, the proton
channels are gated by reversible protonation of key glutamate and lysine residues
and breaking of the water wire connecting the proton pumps with the quinone reduction
site. The tight coupling between the redox and the proton pumping reactions in
transhydrogenase is achieved by controlling the NADP(H) exchange which can only
happen when the NADP(H)-binding domain interacts with the membrane domain. In
complex I, coupling is achieved by cycling of the whole complex between the closed
state, in which quinone can get reduced, and the open state, in which NADH can
induce quinol ejection from the binding pocket. On the basis of these results
I propose detailed mechanisms for catalytic cycles of transhydrogenase and complex
I that are consistent with a large amount of previous work. In both enzymes, conformational
and electrostatic mechanisms contribute to the overall catalytic process. Results
presented here could be used for better understanding of the human pathologies
arising from deficiencies of complex I or transhydrogenase and could be used to
develop novel therapies.
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: 'I acknowledge the support of IST facilities, especially the Electron
Miscroscopy facility for providing training and resources. Special thanks also go
to cryo-EM specialists who helped me to collect the data present here: Dr Valentin
Hodirnau (IST Austria), Dr Tom Heuser (IMBA, Vienna), Dr Rebecca Thompson (Uni.
of Leeds) and Dr Jirka Nováček (CEITEC). This work has been supported by iNEXT,
project number 653706, funded by the Horizon 2020 programme of the European Union.
This project has received funding from the European Union’s Horizon 2020 research
and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665385.'
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Domen
full_name: Kampjut, Domen
id: 37233050-F248-11E8-B48F-1D18A9856A87
last_name: Kampjut
orcid: 0000-0002-6018-3422
citation:
ama: Kampjut D. Molecular mechanisms of mitochondrial redox-coupled proton pumping
enzymes. 2020. doi:10.15479/AT:ISTA:8340
apa: Kampjut, D. (2020). Molecular mechanisms of mitochondrial redox-coupled
proton pumping enzymes. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8340
chicago: Kampjut, Domen. “Molecular Mechanisms of Mitochondrial Redox-Coupled Proton
Pumping Enzymes.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8340.
ieee: D. Kampjut, “Molecular mechanisms of mitochondrial redox-coupled proton pumping
enzymes,” Institute of Science and Technology Austria, 2020.
ista: Kampjut D. 2020. Molecular mechanisms of mitochondrial redox-coupled proton
pumping enzymes. Institute of Science and Technology Austria.
mla: Kampjut, Domen. Molecular Mechanisms of Mitochondrial Redox-Coupled Proton
Pumping Enzymes. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8340.
short: D. Kampjut, Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping
Enzymes, Institute of Science and Technology Austria, 2020.
corr_author: '1'
date_created: 2020-09-07T18:42:23Z
date_published: 2020-09-09T00:00:00Z
date_updated: 2026-04-08T07:43:58Z
day: '09'
ddc:
- '572'
degree_awarded: PhD
department:
- _id: LeSa
doi: 10.15479/AT:ISTA:8340
ec_funded: 1
file:
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language:
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month: '09'
oa: 1
oa_version: None
page: '242'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication_identifier:
isbn:
- 978-3-99078-008-4
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '6848'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
title: Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2020'
...
---
_id: '7652'
abstract:
- lang: eng
text: Organisms cope with change by taking advantage of transcriptional regulators.
However, when faced with rare environments, the evolution of transcriptional regulators
and their promoters may be too slow. Here, we investigate whether the intrinsic
instability of gene duplication and amplification provides a generic alternative
to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations
in Escherichia coli, we show that gene duplications and amplifications enable
adaptation to fluctuating environments by rapidly generating copy-number and,
therefore, expression-level polymorphisms. This amplification-mediated gene expression
tuning (AMGET) occurs on timescales that are similar to canonical gene regulation
and can respond to rapid environmental changes. Mathematical modelling shows that
amplifications also tune gene expression in stochastic environments in which transcription-factor-based
schemes are hard to evolve or maintain. The fleeting nature of gene amplifications
gives rise to a generic population-level mechanism that relies on genetic heterogeneity
to rapidly tune the expression of any gene, without leaving any genomic signature.
acknowledgement: We thank L. Hurst, N. Barton, M. Pleska, M. Steinrück, B. Kavcic
and A. Staron for input on the manuscript, and To. Bergmiller and R. Chait for help
with microfluidics experiments. I.T. is a recipient the OMV fellowship. R.G. is
a recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences)
Fellowship of the Austrian Academy of Sciences.
article_processing_charge: No
article_type: original
author:
- first_name: Isabella
full_name: Tomanek, Isabella
id: 3981F020-F248-11E8-B48F-1D18A9856A87
last_name: Tomanek
orcid: 0000-0001-6197-363X
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: M.
full_name: Lagator, M.
last_name: Lagator
- first_name: A. M. C.
full_name: Andersson, A. M. C.
last_name: Andersson
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Tomanek I, Grah R, Lagator M, et al. Gene amplification as a form of population-level
gene expression regulation. Nature Ecology & Evolution. 2020;4(4):612-625.
doi:10.1038/s41559-020-1132-7
apa: Tomanek, I., Grah, R., Lagator, M., Andersson, A. M. C., Bollback, J. P., Tkačik,
G., & Guet, C. C. (2020). Gene amplification as a form of population-level
gene expression regulation. Nature Ecology & Evolution. Springer Nature.
https://doi.org/10.1038/s41559-020-1132-7
chicago: Tomanek, Isabella, Rok Grah, M. Lagator, A. M. C. Andersson, Jonathan P
Bollback, Gašper Tkačik, and Calin C Guet. “Gene Amplification as a Form of Population-Level
Gene Expression Regulation.” Nature Ecology & Evolution. Springer Nature,
2020. https://doi.org/10.1038/s41559-020-1132-7.
ieee: I. Tomanek et al., “Gene amplification as a form of population-level
gene expression regulation,” Nature Ecology & Evolution, vol. 4, no.
4. Springer Nature, pp. 612–625, 2020.
ista: Tomanek I, Grah R, Lagator M, Andersson AMC, Bollback JP, Tkačik G, Guet CC.
2020. Gene amplification as a form of population-level gene expression regulation.
Nature Ecology & Evolution. 4(4), 612–625.
mla: Tomanek, Isabella, et al. “Gene Amplification as a Form of Population-Level
Gene Expression Regulation.” Nature Ecology & Evolution, vol. 4, no.
4, Springer Nature, 2020, pp. 612–25, doi:10.1038/s41559-020-1132-7.
short: I. Tomanek, R. Grah, M. Lagator, A.M.C. Andersson, J.P. Bollback, G. Tkačik,
C.C. Guet, Nature Ecology & Evolution 4 (2020) 612–625.
date_created: 2020-04-08T15:20:53Z
date_published: 2020-04-01T00:00:00Z
date_updated: 2026-04-26T22:30:48Z
day: '01'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.1038/s41559-020-1132-7
external_id:
isi:
- '000519008300005'
pmid:
- '32152532'
file:
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checksum: ef3bbf42023e30b2c24a6278025d2040
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issue: '4'
language:
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month: '04'
oa: 1
oa_version: Submitted Version
page: 612-625
pmid: 1
project:
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication: Nature Ecology & Evolution
publication_identifier:
issn:
- 2397-334X
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/
record:
- id: '7016'
relation: research_data
status: public
- id: '7383'
relation: research_data
status: public
- id: '8155'
relation: dissertation_contains
status: public
- id: '8653'
relation: used_in_publication
status: public
scopus_import: '1'
status: public
title: Gene amplification as a form of population-level gene expression regulation
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 4
year: '2020'
...
---
OA_place: publisher
_id: '8653'
abstract:
- lang: eng
text: "Mutations are the raw material of evolution and come in many different flavors.
Point mutations change a single letter in the DNA sequence, while copy number
mutations like duplications or deletions add or remove many letters of the DNA
sequence simultaneously. Each type of mutation exhibits specific properties like
its rate of formation and reversal. \r\nGene expression is a fundamental phenotype
that can be altered by both, point and copy number mutations. The following thesis
is concerned with the dynamics of gene expression evolution and how it is affected
by the properties exhibited by point and copy number mutations. Specifically,
we are considering i) copy number mutations during adaptation to fluctuating environments
and ii) the interaction of copy number and point mutations during adaptation to
constant environments. "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Isabella
full_name: Tomanek, Isabella
id: 3981F020-F248-11E8-B48F-1D18A9856A87
last_name: Tomanek
orcid: 0000-0001-6197-363X
citation:
ama: Tomanek I. The evolution of gene expression by copy number and point mutations.
2020. doi:10.15479/AT:ISTA:8653
apa: Tomanek, I. (2020). The evolution of gene expression by copy number and
point mutations. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8653
chicago: Tomanek, Isabella. “The Evolution of Gene Expression by Copy Number and
Point Mutations.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8653.
ieee: I. Tomanek, “The evolution of gene expression by copy number and point mutations,”
Institute of Science and Technology Austria, 2020.
ista: Tomanek I. 2020. The evolution of gene expression by copy number and point
mutations. Institute of Science and Technology Austria.
mla: Tomanek, Isabella. The Evolution of Gene Expression by Copy Number and Point
Mutations. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8653.
short: I. Tomanek, The Evolution of Gene Expression by Copy Number and Point Mutations,
Institute of Science and Technology Austria, 2020.
corr_author: '1'
date_created: 2020-10-13T13:02:33Z
date_published: 2020-10-13T00:00:00Z
date_updated: 2026-04-08T07:29:19Z
day: '13'
ddc:
- '576'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:8653
file:
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file_size: 15405675
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file_date_updated: 2021-10-20T22:30:03Z
has_accepted_license: '1'
keyword:
- duplication
- amplification
- promoter
- CNV
- AMGET
- experimental evolution
- Escherichia coli
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '117'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7652'
relation: research_data
status: public
status: public
supervisor:
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
title: The evolution of gene expression by copy number and point mutations
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2020'
...
---
OA_place: publisher
_id: '8620'
abstract:
- lang: eng
text: "The development of the human brain occurs through a tightly regulated series
of dynamic and adaptive processes during prenatal and postnatal life. A disruption
of this strictly orchestrated series of events can lead to a number of neurodevelopmental
conditions, including Autism Spectrum Disorders (ASDs). ASDs are a very common,
etiologically and phenotypically heterogeneous group of disorders sharing the
core symptoms of social interaction and communication deficits and restrictive
and repetitive interests and behaviors. They are estimated to affect one in 59
individuals in the U.S. and, over the last three decades, mutations in more than
a hundred genetic loci have been convincingly linked to ASD pathogenesis. Yet,
for the vast majority of these ASD-risk genes their role during brain development
and precise molecular function still remain elusive.\r\nDe novo loss of function
mutations in the ubiquitin ligase-encoding gene Cullin 3 (CUL3) lead to ASD. In
the study described here, we used Cul3 mouse models to evaluate the consequences
of Cul3 mutations in vivo. Our results show that Cul3 heterozygous knockout mice
exhibit deficits in motor coordination as well as ASD-relevant social and cognitive
impairments. Cul3+/-, Cul3+/fl Emx1-Cre and Cul3fl/fl Emx1-Cre mutant brains display
cortical lamination abnormalities due to defective migration of post-mitotic excitatory
neurons, as well as reduced numbers of excitatory and inhibitory neurons. In line
with the observed abnormal cortical organization, Cul3 heterozygous deletion is
associated with decreased spontaneous excitatory and inhibitory activity in the
cortex. At the molecular level we show that Cul3 regulates cytoskeletal and adhesion
protein abundance in the mouse embryonic cortex. Abnormal regulation of cytoskeletal
proteins in Cul3 mutant neural cells results in atypical organization of the actin
mesh at the cell leading edge. Of note, heterozygous deletion of Cul3 in adult
mice does not induce the majority of the behavioral defects observed in constitutive
Cul3 haploinsufficient animals, pointing to a critical time-window for Cul3 deficiency.\r\nIn
conclusion, our data indicate that Cul3 plays a critical role in the regulation
of cytoskeletal proteins and neuronal migration. ASD-associated defects and behavioral
abnormalities are primarily due to dosage sensitive Cul3 functions at early brain
developmental stages."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: I would like to especially thank Armel Nicolas from the Proteomics
and Christoph Sommer from the Bioimaging Facilities for the data analysis, and to
thank the team of the Preclinical Facility, especially Sabina Deixler, Angela Schlerka,
Anita Lepold, Mihalea Mihai and Michael Schun for taking care of the mouse line
maintenance and their great support.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
citation:
ama: Morandell J. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis.
2020. doi:10.15479/AT:ISTA:8620
apa: Morandell, J. (2020). Illuminating the role of Cul3 in autism spectrum disorder
pathogenesis. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8620
chicago: Morandell, Jasmin. “Illuminating the Role of Cul3 in Autism Spectrum Disorder
Pathogenesis.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8620.
ieee: J. Morandell, “Illuminating the role of Cul3 in autism spectrum disorder pathogenesis,”
Institute of Science and Technology Austria, 2020.
ista: Morandell J. 2020. Illuminating the role of Cul3 in autism spectrum disorder
pathogenesis. Institute of Science and Technology Austria.
mla: Morandell, Jasmin. Illuminating the Role of Cul3 in Autism Spectrum Disorder
Pathogenesis. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8620.
short: J. Morandell, Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis,
Institute of Science and Technology Austria, 2020.
corr_author: '1'
date_created: 2020-10-07T14:53:13Z
date_published: 2020-10-12T00:00:00Z
date_updated: 2026-04-14T09:07:16Z
day: '12'
ddc:
- '610'
degree_awarded: PhD
department:
- _id: GaNo
doi: 10.15479/AT:ISTA:8620
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project:
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call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F7807
name: Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem
cells in autism and epilepsy
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
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relation: part_of_dissertation
status: public
- id: '8131'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
title: Illuminating the role of Cul3 in autism spectrum disorder pathogenesis
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2020'
...
---
_id: '7800'
abstract:
- lang: eng
text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
(CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models
to evaluate the consequences of Cul3 mutations in vivo. Our results show that
Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as
ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical
lamination abnormalities due to defective neuronal migration and reduced numbers
of excitatory and inhibitory neurons. In line with the observed abnormal columnar
organization, Cul3 haploinsufficiency is associated with decreased spontaneous
excitatory and inhibitory activity in the cortex. At the molecular level, employing
a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and
adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal
proteins in Cul3 mutant neuronal cells results in atypical organization of the
actin mesh at the cell leading edge, likely causing the observed migration deficits.
In contrast to these important functions early in development, Cul3 deficiency
appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency
in adult mice does not result in the behavioral defects observed in constitutive
Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has
a critical role in the regulation of cytoskeletal proteins and neuronal migration
and that ASD-associated defects and behavioral abnormalities are primarily due
to Cul3 functions at early developmental stages.
acknowledged_ssus:
- _id: PreCl
article_processing_charge: No
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Zoe
full_name: Dobler, Zoe
id: D23090A2-9057-11EA-883A-A8396FC7A38F
last_name: Dobler
- first_name: Emanuele
full_name: Cacci, Emanuele
last_name: Cacci
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein
homeostasis and cell migration during a critical window of brain development.
bioRxiv. doi:10.1101/2020.01.10.902064
apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer,
C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development. bioRxiv.
Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.01.10.902064
chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates
Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of
Brain Development.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.01.10.902064 .
ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development,” bioRxiv.
Cold Spring Harbor Laboratory.
ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger
C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton
protein homeostasis and cell migration during a critical window of brain development.
bioRxiv, 10.1101/2020.01.10.902064
.
mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
and Cell Migration during a Critical Window of Brain Development.” BioRxiv,
Cold Spring Harbor Laboratory, doi:10.1101/2020.01.10.902064 .
short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer,
C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv
(n.d.).
corr_author: '1'
date_created: 2020-05-05T14:31:33Z
date_published: 2020-01-11T00:00:00Z
date_updated: 2026-04-26T22:30:55Z
day: '11'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
- _id: LifeSc
doi: '10.1101/2020.01.10.902064 '
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language:
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month: '01'
oa: 1
oa_version: Preprint
project:
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publication: bioRxiv
publication_status: draft
publisher: Cold Spring Harbor Laboratory
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status: public
title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a
critical window of brain development
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
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short: CC BY-NC-ND (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
OA_place: repository
OA_type: green
_id: '7885'
abstract:
- lang: eng
text: Eukaryotic cells migrate by coupling the intracellular force of the actin
cytoskeleton to the environment. While force coupling is usually mediated by transmembrane
adhesion receptors, especially those of the integrin family, amoeboid cells such
as leukocytes can migrate extremely fast despite very low adhesive forces1. Here
we show that leukocytes cannot only migrate under low adhesion but can also transmit
forces in the complete absence of transmembrane force coupling. When confined
within three-dimensional environments, they use the topographical features of
the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton
follows the texture of the substrate, creating retrograde shear forces that are
sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent
migration are not mutually exclusive, but rather are variants of the same principle
of coupling retrograde actin flow to the environment and thus can potentially
operate interchangeably and simultaneously. As adhesion-free migration is independent
of the chemical composition of the environment, it renders cells completely autonomous
in their locomotive behaviour.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
acknowledgement: We thank A. Leithner and J. Renkawitz for discussion and critical
reading of the manuscript; J. Schwarz and M. Mehling for establishing the microfluidic
setups; the Bioimaging Facility of IST Austria for excellent support, as well as
the Life Science Facility and the Miba Machine Shop of IST Austria; and F. N. Arslan,
L. E. Burnett and L. Li for their work during their rotation in the IST PhD programme.
This work was supported by the European Research Council (ERC StG 281556 and CoG
724373) to M.S. and grants from the Austrian Science Fund (FWF P29911) and the WWTF
to M.S. M.H. was supported by the European Regional Development Fund Project (CZ.02.1.01/0.0/0.0/15_003/0000476).
F.G. received funding from the European Union’s Horizon 2020 research and innovation
programme under the Marie Skłodowska-Curie grant agreement no. 747687.
article_processing_charge: No
article_type: original
author:
- first_name: Anne
full_name: Reversat, Anne
id: 35B76592-F248-11E8-B48F-1D18A9856A87
last_name: Reversat
orcid: 0000-0003-0666-8928
- first_name: Florian R
full_name: Gärtner, Florian R
id: 397A88EE-F248-11E8-B48F-1D18A9856A87
last_name: Gärtner
orcid: 0000-0001-6120-3723
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Juan L
full_name: Aguilera Servin, Juan L
id: 2A67C376-F248-11E8-B48F-1D18A9856A87
last_name: Aguilera Servin
orcid: 0000-0002-2862-8372
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Matthieu
full_name: Piel, Matthieu
last_name: Piel
- first_name: Andrew
full_name: Callan-Jones, Andrew
last_name: Callan-Jones
- first_name: Raphael
full_name: Voituriez, Raphael
last_name: Voituriez
- 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: Reversat A, Gärtner FR, Merrin J, et al. Cellular locomotion using environmental
topography. Nature. 2020;582:582–585. doi:10.1038/s41586-020-2283-z
apa: Reversat, A., Gärtner, F. R., Merrin, J., Stopp, J. A., Tasciyan, S., Aguilera
Servin, J. L., … Sixt, M. K. (2020). Cellular locomotion using environmental topography.
Nature. Springer Nature. https://doi.org/10.1038/s41586-020-2283-z
chicago: Reversat, Anne, Florian R Gärtner, Jack Merrin, Julian A Stopp, Saren Tasciyan,
Juan L Aguilera Servin, Ingrid de Vries, et al. “Cellular Locomotion Using Environmental
Topography.” Nature. Springer Nature, 2020. https://doi.org/10.1038/s41586-020-2283-z.
ieee: A. Reversat et al., “Cellular locomotion using environmental topography,”
Nature, vol. 582. Springer Nature, pp. 582–585, 2020.
ista: Reversat A, Gärtner FR, Merrin J, Stopp JA, Tasciyan S, Aguilera Servin JL,
de Vries I, Hauschild R, Hons M, Piel M, Callan-Jones A, Voituriez R, Sixt MK.
2020. Cellular locomotion using environmental topography. Nature. 582, 582–585.
mla: Reversat, Anne, et al. “Cellular Locomotion Using Environmental Topography.”
Nature, vol. 582, Springer Nature, 2020, pp. 582–585, doi:10.1038/s41586-020-2283-z.
short: A. Reversat, F.R. Gärtner, J. Merrin, J.A. Stopp, S. Tasciyan, J.L. Aguilera
Servin, I. de Vries, R. Hauschild, M. Hons, M. Piel, A. Callan-Jones, R. Voituriez,
M.K. Sixt, Nature 582 (2020) 582–585.
date_created: 2020-05-24T22:01:01Z
date_published: 2020-06-25T00:00:00Z
date_updated: 2026-04-26T22:30:56Z
day: '25'
department:
- _id: NanoFab
- _id: Bio
- _id: MiSi
doi: 10.1038/s41586-020-2283-z
ec_funded: 1
external_id:
isi:
- '000532688300008'
pmid:
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intvolume: ' 582'
isi: 1
language:
- iso: eng
main_file_link:
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url: https://doi.org/10.1101/793919
month: '06'
oa: 1
oa_version: Preprint
page: 582–585
pmid: 1
project:
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call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
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call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
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call_identifier: H2020
grant_number: '747687'
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publication: Nature
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eissn:
- 1476-4687
issn:
- 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
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relation: press_release
url: https://ist.ac.at/en/news/off-road-mode-enables-mobile-cells-to-move-freely/
record:
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relation: dissertation_contains
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scopus_import: '1'
status: public
title: Cellular locomotion using environmental topography
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 582
year: '2020'
...
---
_id: '8131'
abstract:
- lang: eng
text: The possibility to generate construct valid animal models enabled the development
and testing of therapeutic strategies targeting the core features of autism spectrum
disorders (ASDs). At the same time, these studies highlighted the necessity of
identifying sensitive developmental time windows for successful therapeutic interventions.
Animal and human studies also uncovered the possibility to stratify the variety
of ASDs in molecularly distinct subgroups, potentially facilitating effective
treatment design. Here, we focus on the molecular pathways emerging as commonly
affected by mutations in diverse ASD-risk genes, on their role during critical
windows of brain development and the potential treatments targeting these biological
processes.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Basilico B, Morandell J, Novarino G. Molecular mechanisms for targeted ASD
treatments. Current Opinion in Genetics and Development. 2020;65(12):126-137.
doi:10.1016/j.gde.2020.06.004
apa: Basilico, B., Morandell, J., & Novarino, G. (2020). Molecular mechanisms
for targeted ASD treatments. Current Opinion in Genetics and Development.
Elsevier. https://doi.org/10.1016/j.gde.2020.06.004
chicago: Basilico, Bernadette, Jasmin Morandell, and Gaia Novarino. “Molecular Mechanisms
for Targeted ASD Treatments.” Current Opinion in Genetics and Development.
Elsevier, 2020. https://doi.org/10.1016/j.gde.2020.06.004.
ieee: B. Basilico, J. Morandell, and G. Novarino, “Molecular mechanisms for targeted
ASD treatments,” Current Opinion in Genetics and Development, vol. 65,
no. 12. Elsevier, pp. 126–137, 2020.
ista: Basilico B, Morandell J, Novarino G. 2020. Molecular mechanisms for targeted
ASD treatments. Current Opinion in Genetics and Development. 65(12), 126–137.
mla: Basilico, Bernadette, et al. “Molecular Mechanisms for Targeted ASD Treatments.”
Current Opinion in Genetics and Development, vol. 65, no. 12, Elsevier,
2020, pp. 126–37, doi:10.1016/j.gde.2020.06.004.
short: B. Basilico, J. Morandell, G. Novarino, Current Opinion in Genetics and Development
65 (2020) 126–137.
corr_author: '1'
date_created: 2020-07-19T22:00:58Z
date_published: 2020-12-01T00:00:00Z
date_updated: 2026-04-26T22:30:56Z
day: '01'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1016/j.gde.2020.06.004
ec_funded: 1
external_id:
isi:
- '000598918900019'
pmid:
- '32659636'
file:
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date_updated: 2020-07-22T06:47:45Z
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file_name: 2020_CurrentOpGenetics_Basilico.pdf
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relation: main_file
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file_date_updated: 2020-07-22T06:47:45Z
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issue: '12'
language:
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month: '12'
oa: 1
oa_version: Published Version
page: 126-137
pmid: 1
project:
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call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
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call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F7807
name: Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem
cells in autism and epilepsy
publication: Current Opinion in Genetics and Development
publication_identifier:
eissn:
- 1879-0380
issn:
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publisher: Elsevier
quality_controlled: '1'
related_material:
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scopus_import: '1'
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title: Molecular mechanisms for targeted ASD treatments
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
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short: CC BY-NC-ND (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 65
year: '2020'
...
---
_id: '7815'
abstract:
- lang: eng
text: Beginning from a limited pool of progenitors, the mammalian cerebral cortex
forms highly organized functional neural circuits. However, the underlying cellular
and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs)
and eventual production of neurons and glia in the developing neuroepithelium
remains unclear. Methods to trace NSC division patterns and map the lineage of
clonally related cells have advanced dramatically. However, many contemporary
lineage tracing techniques suffer from the lack of cellular resolution of progeny
cell fate, which is essential for deciphering progenitor cell division patterns.
Presented is a protocol using mosaic analysis with double markers (MADM) to perform
in vivo clonal analysis. MADM concomitantly manipulates individual progenitor
cells and visualizes precise division patterns and lineage progression at unprecedented
single cell resolution. MADM-based interchromosomal recombination events during
the G2-X phase of mitosis, together with temporally inducible CreERT2, provide
exact information on the birth dates of clones and their division patterns. Thus,
MADM lineage tracing provides unprecedented qualitative and quantitative optical
readouts of the proliferation mode of stem cell progenitors at the single cell
level. MADM also allows for examination of the mechanisms and functional requirements
of candidate genes in NSC lineage progression. This method is unique in that comparative
analysis of control and mutant subclones can be performed in the same tissue environment
in vivo. Here, the protocol is described in detail, and experimental paradigms
to employ MADM for clonal analysis and lineage tracing in the developing cerebral
cortex are demonstrated. Importantly, this protocol can be adapted to perform
MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver
is present.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
article_number: e61147
article_processing_charge: No
article_type: original
author:
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Giselle T
full_name: Cheung, Giselle T
id: 471195F6-F248-11E8-B48F-1D18A9856A87
last_name: Cheung
orcid: 0000-0001-8457-2572
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis
in developing cerebral cortex using mosaic analysis with double markers (MADM).
Journal of Visual Experiments. 2020;(159). doi:10.3791/61147
apa: Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen,
A. H., & Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing
cerebral cortex using mosaic analysis with double markers (MADM). Journal of
Visual Experiments. MyJove Corporation. https://doi.org/10.3791/61147
chicago: Beattie, Robert J, Carmen Streicher, Nicole Amberg, Giselle T Cheung, Ximena
Contreras, Andi H Hansen, and Simon Hippenmeyer. “Lineage Tracing and Clonal Analysis
in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).”
Journal of Visual Experiments. MyJove Corporation, 2020. https://doi.org/10.3791/61147.
ieee: R. J. Beattie et al., “Lineage tracing and clonal analysis in developing
cerebral cortex using mosaic analysis with double markers (MADM),” Journal
of Visual Experiments, no. 159. MyJove Corporation, 2020.
ista: Beattie RJ, Streicher C, Amberg N, Cheung GT, Contreras X, Hansen AH, Hippenmeyer
S. 2020. Lineage tracing and clonal analysis in developing cerebral cortex using
mosaic analysis with double markers (MADM). Journal of Visual Experiments. (159),
e61147.
mla: Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing
Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” Journal
of Visual Experiments, no. 159, e61147, MyJove Corporation, 2020, doi:10.3791/61147.
short: R.J. Beattie, C. Streicher, N. Amberg, G.T. Cheung, X. Contreras, A.H. Hansen,
S. Hippenmeyer, Journal of Visual Experiments (2020).
corr_author: '1'
date_created: 2020-05-11T08:31:20Z
date_published: 2020-05-08T00:00:00Z
date_updated: 2026-04-26T22:30:59Z
day: '08'
ddc:
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department:
- _id: SiHi
doi: 10.3791/61147
ec_funded: 1
external_id:
isi:
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month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Neocortex
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T01031
name: Role of Eed in neural stem cell lineage progression
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular mechanisms of radial neuronal migration
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Journal of Visual Experiments
publication_identifier:
issn:
- 1940-087X
publication_status: published
publisher: MyJove Corporation
quality_controlled: '1'
related_material:
record:
- id: '7902'
relation: part_of_dissertation
status: public
scopus_import: '1'
status: public
title: Lineage tracing and clonal analysis in developing cerebral cortex using mosaic
analysis with double markers (MADM)
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
year: '2020'
...
---
OA_place: publisher
_id: '7902'
abstract:
- lang: eng
text: "Mosaic genetic analysis has been widely used in different model organisms
such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific
fashion. More recently, and less easily conducted, mosaic genetic analysis in
mice has also been enabled with the ambition to shed light on human gene function
and disease. These genetic tools are of particular interest, but not restricted
to, the study of the brain. Notably, the MADM technology offers a genetic approach
in mice to visualize and concomitantly manipulate small subsets of genetically
defined cells at a clonal level and single cell resolution. MADM-based analysis
has already advanced the study of genetic mechanisms regulating brain development
and is expected that further MADM-based analysis of genetic alterations will continue
to reveal important insights on the fundamental principles of development and
disease to potentially assist in the development of new therapies or treatments.\r\nIn
summary, this work completed and characterized the necessary genome-wide genetic
tools to perform MADM-based analysis at single cell level of the vast majority
of mouse genes in virtually any cell type and provided a protocol to perform lineage
tracing using the novel MADM resource. Importantly, this work also explored and
revealed novel aspects of biologically relevant events in an in vivo context,
such as the chromosome-specific bias of chromatid sister segregation pattern,
the generation of cell-type diversity in the cerebral cortex and in the cerebellum
and finally, the relevance of the interplay between the cell-autonomous gene function
and cell-non-autonomous (community) effects in radial glial progenitor lineage
progression.\r\nThis work provides a foundation and opens the door to further
elucidating the molecular mechanisms underlying neuronal diversity and astrocyte
generation."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
citation:
ama: Contreras X. Genetic dissection of neural development in health and disease
at single cell resolution. 2020. doi:10.15479/AT:ISTA:7902
apa: Contreras, X. (2020). Genetic dissection of neural development in health
and disease at single cell resolution. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:7902
chicago: Contreras, Ximena. “Genetic Dissection of Neural Development in Health
and Disease at Single Cell Resolution.” Institute of Science and Technology Austria,
2020. https://doi.org/10.15479/AT:ISTA:7902.
ieee: X. Contreras, “Genetic dissection of neural development in health and disease
at single cell resolution,” Institute of Science and Technology Austria, 2020.
ista: Contreras X. 2020. Genetic dissection of neural development in health and
disease at single cell resolution. Institute of Science and Technology Austria.
mla: Contreras, Ximena. Genetic Dissection of Neural Development in Health and
Disease at Single Cell Resolution. Institute of Science and Technology Austria,
2020, doi:10.15479/AT:ISTA:7902.
short: X. Contreras, Genetic Dissection of Neural Development in Health and Disease
at Single Cell Resolution, Institute of Science and Technology Austria, 2020.
corr_author: '1'
date_created: 2020-05-29T08:27:32Z
date_published: 2020-06-05T00:00:00Z
date_updated: 2026-04-16T09:52:49Z
day: '05'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: SiHi
doi: 10.15479/AT:ISTA:7902
ec_funded: 1
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date_updated: 2021-06-07T22:30:03Z
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file_size: 53134142
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language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '214'
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '28'
relation: dissertation_contains
status: public
- id: '7815'
relation: dissertation_contains
status: public
- id: '6830'
relation: dissertation_contains
status: public
status: public
supervisor:
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
title: Genetic dissection of neural development in health and disease at single cell
resolution
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2020'
...
---
_id: '7810'
abstract:
- lang: eng
text: "Interprocedural data-flow analyses form an expressive and useful paradigm
of numerous static analysis applications, such as live variables analysis, alias
analysis and null pointers analysis. The most widely-used framework for interprocedural
data-flow analysis is IFDS, which encompasses distributive data-flow functions
over a finite domain. On-demand data-flow analyses restrict the focus of the analysis
on specific program locations and data facts. This setting provides a natural
split between (i) an offline (or preprocessing) phase, where the program is partially
analyzed and analysis summaries are created, and (ii) an online (or query) phase,
where analysis queries arrive on demand and the summaries are used to speed up
answering queries.\r\nIn this work, we consider on-demand IFDS analyses where
the queries concern program locations of the same procedure (aka same-context
queries). We exploit the fact that flow graphs of programs have low treewidth
to develop faster algorithms that are space and time optimal for many common data-flow
analyses, in both the preprocessing and the query phase. We also use treewidth
to develop query solutions that are embarrassingly parallelizable, i.e. the total
work for answering each query is split to a number of threads such that each thread
performs only a constant amount of work. Finally, we implement a static analyzer
based on our algorithms, and perform a series of on-demand analysis experiments
on standard benchmarks. Our experimental results show a drastic speed-up of the
queries after only a lightweight preprocessing phase, which significantly outperforms
existing techniques."
alternative_title:
- LNCS
article_processing_charge: No
author:
- first_name: Krishnendu
full_name: Chatterjee, Krishnendu
id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87
last_name: Chatterjee
orcid: 0000-0002-4561-241X
- first_name: Amir Kafshdar
full_name: Goharshady, Amir Kafshdar
id: 391365CE-F248-11E8-B48F-1D18A9856A87
last_name: Goharshady
orcid: 0000-0003-1702-6584
- first_name: Rasmus
full_name: Ibsen-Jensen, Rasmus
id: 3B699956-F248-11E8-B48F-1D18A9856A87
last_name: Ibsen-Jensen
orcid: 0000-0003-4783-0389
- first_name: Andreas
full_name: Pavlogiannis, Andreas
id: 49704004-F248-11E8-B48F-1D18A9856A87
last_name: Pavlogiannis
orcid: 0000-0002-8943-0722
citation:
ama: 'Chatterjee K, Goharshady AK, Ibsen-Jensen R, Pavlogiannis A. Optimal and perfectly
parallel algorithms for on-demand data-flow analysis. In: European Symposium
on Programming. Vol 12075. Springer Nature; 2020:112-140. doi:10.1007/978-3-030-44914-8_5'
apa: 'Chatterjee, K., Goharshady, A. K., Ibsen-Jensen, R., & Pavlogiannis, A.
(2020). Optimal and perfectly parallel algorithms for on-demand data-flow analysis.
In European Symposium on Programming (Vol. 12075, pp. 112–140). Dublin,
Ireland: Springer Nature. https://doi.org/10.1007/978-3-030-44914-8_5'
chicago: Chatterjee, Krishnendu, Amir Kafshdar Goharshady, Rasmus Ibsen-Jensen,
and Andreas Pavlogiannis. “Optimal and Perfectly Parallel Algorithms for On-Demand
Data-Flow Analysis.” In European Symposium on Programming, 12075:112–40.
Springer Nature, 2020. https://doi.org/10.1007/978-3-030-44914-8_5.
ieee: K. Chatterjee, A. K. Goharshady, R. Ibsen-Jensen, and A. Pavlogiannis, “Optimal
and perfectly parallel algorithms for on-demand data-flow analysis,” in European
Symposium on Programming, Dublin, Ireland, 2020, vol. 12075, pp. 112–140.
ista: 'Chatterjee K, Goharshady AK, Ibsen-Jensen R, Pavlogiannis A. 2020. Optimal
and perfectly parallel algorithms for on-demand data-flow analysis. European Symposium
on Programming. ESOP: Programming Languages and Systems, LNCS, vol. 12075, 112–140.'
mla: Chatterjee, Krishnendu, et al. “Optimal and Perfectly Parallel Algorithms for
On-Demand Data-Flow Analysis.” European Symposium on Programming, vol.
12075, Springer Nature, 2020, pp. 112–40, doi:10.1007/978-3-030-44914-8_5.
short: K. Chatterjee, A.K. Goharshady, R. Ibsen-Jensen, A. Pavlogiannis, in:, European
Symposium on Programming, Springer Nature, 2020, pp. 112–140.
conference:
end_date: 2020-04-30
location: Dublin, Ireland
name: 'ESOP: Programming Languages and Systems'
start_date: 2020-04-25
corr_author: '1'
date_created: 2020-05-10T22:00:50Z
date_published: 2020-04-18T00:00:00Z
date_updated: 2026-04-26T22:31:03Z
day: '18'
ddc:
- '000'
department:
- _id: KrCh
doi: 10.1007/978-3-030-44914-8_5
external_id:
isi:
- '000681656800005'
file:
- access_level: open_access
checksum: 8618b80f4cf7b39a60e61a6445ad9807
content_type: application/pdf
creator: dernst
date_created: 2020-05-26T13:34:48Z
date_updated: 2020-07-14T12:48:03Z
file_id: '7895'
file_name: 2020_LNCS_Chatterjee.pdf
file_size: 651250
relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
intvolume: ' 12075'
isi: 1
language:
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month: '04'
oa: 1
oa_version: Published Version
page: 112-140
project:
- _id: 25832EC2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: S 11407_N23
name: Rigorous Systems Engineering
- _id: 25892FC0-B435-11E9-9278-68D0E5697425
grant_number: ICT15-003
name: Efficient Algorithms for Computer Aided Verification
- _id: 266EEEC0-B435-11E9-9278-68D0E5697425
name: Quantitative Game-theoretic Analysis of Blockchain Applications and Smart
Contracts
- _id: 267066CE-B435-11E9-9278-68D0E5697425
name: Quantitative Analysis of Probabilistic Systems with a focus on Crypto-Currencies
publication: European Symposium on Programming
publication_identifier:
eissn:
- 1611-3349
isbn:
- '9783030449131'
issn:
- 0302-9743
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
record:
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relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Optimal and perfectly parallel algorithms for on-demand data-flow analysis
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: conference
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 12075
year: '2020'
...
---
_id: '8728'
abstract:
- lang: eng
text: Discrete-time Markov Chains (MCs) and Markov Decision Processes (MDPs) are
two standard formalisms in system analysis. Their main associated quantitative
objectives are hitting probabilities, discounted sum, and mean payoff. Although
there are many techniques for computing these objectives in general MCs/MDPs,
they have not been thoroughly studied in terms of parameterized algorithms, particularly
when treewidth is used as the parameter. This is in sharp contrast to qualitative
objectives for MCs, MDPs and graph games, for which treewidth-based algorithms
yield significant complexity improvements. In this work, we show that treewidth
can also be used to obtain faster algorithms for the quantitative problems. For
an MC with n states and m transitions, we show that each of the classical quantitative
objectives can be computed in O((n+m)⋅t2) time, given a tree decomposition
of the MC with width t. Our results also imply a bound of O(κ⋅(n+m)⋅t2) for
each objective on MDPs, where κ is the number of strategy-iteration refinements
required for the given input and objective. Finally, we make an experimental evaluation
of our new algorithms on low-treewidth MCs and MDPs obtained from the DaCapo benchmark
suite. Our experiments show that on low-treewidth MCs and MDPs, our algorithms
outperform existing well-established methods by one or more orders of magnitude.
alternative_title:
- LNCS
article_processing_charge: No
author:
- first_name: Ali
full_name: Asadi, Ali
last_name: Asadi
- first_name: Krishnendu
full_name: Chatterjee, Krishnendu
id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87
last_name: Chatterjee
orcid: 0000-0002-4561-241X
- first_name: Amir Kafshdar
full_name: Goharshady, Amir Kafshdar
id: 391365CE-F248-11E8-B48F-1D18A9856A87
last_name: Goharshady
orcid: 0000-0003-1702-6584
- first_name: Kiarash
full_name: Mohammadi, Kiarash
last_name: Mohammadi
- first_name: Andreas
full_name: Pavlogiannis, Andreas
id: 49704004-F248-11E8-B48F-1D18A9856A87
last_name: Pavlogiannis
orcid: 0000-0002-8943-0722
citation:
ama: 'Asadi A, Chatterjee K, Goharshady AK, Mohammadi K, Pavlogiannis A. Faster
algorithms for quantitative analysis of MCs and MDPs with small treewidth. In:
Automated Technology for Verification and Analysis. Vol 12302. Springer
Nature; 2020:253-270. doi:10.1007/978-3-030-59152-6_14'
apa: 'Asadi, A., Chatterjee, K., Goharshady, A. K., Mohammadi, K., & Pavlogiannis,
A. (2020). Faster algorithms for quantitative analysis of MCs and MDPs with small
treewidth. In Automated Technology for Verification and Analysis (Vol.
12302, pp. 253–270). Hanoi, Vietnam: Springer Nature. https://doi.org/10.1007/978-3-030-59152-6_14'
chicago: Asadi, Ali, Krishnendu Chatterjee, Amir Kafshdar Goharshady, Kiarash Mohammadi,
and Andreas Pavlogiannis. “Faster Algorithms for Quantitative Analysis of MCs
and MDPs with Small Treewidth.” In Automated Technology for Verification and
Analysis, 12302:253–70. Springer Nature, 2020. https://doi.org/10.1007/978-3-030-59152-6_14.
ieee: A. Asadi, K. Chatterjee, A. K. Goharshady, K. Mohammadi, and A. Pavlogiannis,
“Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth,”
in Automated Technology for Verification and Analysis, Hanoi, Vietnam,
2020, vol. 12302, pp. 253–270.
ista: 'Asadi A, Chatterjee K, Goharshady AK, Mohammadi K, Pavlogiannis A. 2020.
Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth.
Automated Technology for Verification and Analysis. ATVA: Automated Technology
for Verification and Analysis, LNCS, vol. 12302, 253–270.'
mla: Asadi, Ali, et al. “Faster Algorithms for Quantitative Analysis of MCs and
MDPs with Small Treewidth.” Automated Technology for Verification and Analysis,
vol. 12302, Springer Nature, 2020, pp. 253–70, doi:10.1007/978-3-030-59152-6_14.
short: A. Asadi, K. Chatterjee, A.K. Goharshady, K. Mohammadi, A. Pavlogiannis,
in:, Automated Technology for Verification and Analysis, Springer Nature, 2020,
pp. 253–270.
conference:
end_date: 2020-10-23
location: Hanoi, Vietnam
name: 'ATVA: Automated Technology for Verification and Analysis'
start_date: 2020-10-19
date_created: 2020-11-06T07:30:05Z
date_published: 2020-10-12T00:00:00Z
date_updated: 2026-04-26T22:31:03Z
day: '12'
ddc:
- '000'
department:
- _id: KrCh
doi: 10.1007/978-3-030-59152-6_14
external_id:
isi:
- '000723555700014'
file:
- access_level: open_access
checksum: ae83f27e5b189d5abc2e7514f1b7e1b5
content_type: application/pdf
creator: dernst
date_created: 2020-11-06T07:41:03Z
date_updated: 2020-11-06T07:41:03Z
file_id: '8729'
file_name: 2020_LNCS_ATVA_Asadi_accepted.pdf
file_size: 726648
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success: 1
file_date_updated: 2020-11-06T07:41:03Z
has_accepted_license: '1'
intvolume: ' 12302'
isi: 1
language:
- iso: eng
month: '10'
oa: 1
oa_version: Submitted Version
page: 253-270
project:
- _id: 25832EC2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: S 11407_N23
name: Rigorous Systems Engineering
- _id: 25892FC0-B435-11E9-9278-68D0E5697425
grant_number: ICT15-003
name: Efficient Algorithms for Computer Aided Verification
- _id: 267066CE-B435-11E9-9278-68D0E5697425
name: Quantitative Analysis of Probabilistic Systems with a focus on Crypto-Currencies
publication: Automated Technology for Verification and Analysis
publication_identifier:
eisbn:
- '9783030591526'
eissn:
- 1611-3349
isbn:
- '9783030591519'
issn:
- 0302-9743
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
record:
- id: '8934'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth
type: conference
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 12302
year: '2020'
...