---
_id: '8586'
abstract:
- lang: eng
text: Cryo-electron microscopy (cryo-EM) of cellular specimens provides insights
into biological processes and structures within a native context. However, a major
challenge still lies in the efficient and reproducible preparation of adherent
cells for subsequent cryo-EM analysis. This is due to the sensitivity of many
cellular specimens to the varying seeding and culturing conditions required for
EM experiments, the often limited amount of cellular material and also the fragility
of EM grids and their substrate. Here, we present low-cost and reusable 3D printed
grid holders, designed to improve specimen preparation when culturing challenging
cellular samples directly on grids. The described grid holders increase cell culture
reproducibility and throughput, and reduce the resources required for cell culturing.
We show that grid holders can be integrated into various cryo-EM workflows, including
micro-patterning approaches to control cell seeding on grids, and for generating
samples for cryo-focused ion beam milling and cryo-electron tomography experiments.
Their adaptable design allows for the generation of specialized grid holders customized
to a large variety of applications.
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: This work was supported by the Austrian Science Fund (FWF, P33367)
to FKMS. BZ acknowledges support by the Niederösterreich Fond. This research was
also supported by the Scientific Service Units (SSU) of IST Austria through resources
provided by Scientific Computing (SciComp), the Life Science Facility (LSF), the
BioImaging Facility (BIF) and the Electron Microscopy Facility (EMF). We thank Georgi
Dimchev (IST Austria) and Sonja Jacob (Vienna Biocenter Core Facilities) for testing
our grid holders in different experimental setups and Daniel Gütl and the Kondrashov
group (IST Austria) for granting us repeated access to their 3D printers. We also
thank Jonna Alanko and the Sixt lab (IST Austria) for providing us HeLa cells, primary
BL6 mouse tail fibroblasts, NIH 3T3 fibroblasts and human telomerase immortalised
foreskin fibroblasts for our experiments. We are thankful to Ori Avinoam and William
Wan for helpful comments on the manuscript and also thank Dorotea Fracchiolla (Art&Science)
for illustrating the graphical abstract.
article_number: '107633'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Florian
full_name: Fäßler, Florian
id: 404F5528-F248-11E8-B48F-1D18A9856A87
last_name: Fäßler
orcid: 0000-0001-7149-769X
- first_name: Bettina
full_name: Zens, Bettina
id: 45FD126C-F248-11E8-B48F-1D18A9856A87
last_name: Zens
orcid: 0000-0002-9561-1239
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
citation:
ama: Fäßler F, Zens B, Hauschild R, Schur FK. 3D printed cell culture grid holders
for improved cellular specimen preparation in cryo-electron microscopy. Journal
of Structural Biology. 2020;212(3). doi:10.1016/j.jsb.2020.107633
apa: Fäßler, F., Zens, B., Hauschild, R., & Schur, F. K. (2020). 3D printed
cell culture grid holders for improved cellular specimen preparation in cryo-electron
microscopy. Journal of Structural Biology. Elsevier. https://doi.org/10.1016/j.jsb.2020.107633
chicago: Fäßler, Florian, Bettina Zens, Robert Hauschild, and Florian KM Schur.
“3D Printed Cell Culture Grid Holders for Improved Cellular Specimen Preparation
in Cryo-Electron Microscopy.” Journal of Structural Biology. Elsevier,
2020. https://doi.org/10.1016/j.jsb.2020.107633.
ieee: F. Fäßler, B. Zens, R. Hauschild, and F. K. Schur, “3D printed cell culture
grid holders for improved cellular specimen preparation in cryo-electron microscopy,”
Journal of Structural Biology, vol. 212, no. 3. Elsevier, 2020.
ista: Fäßler F, Zens B, Hauschild R, Schur FK. 2020. 3D printed cell culture grid
holders for improved cellular specimen preparation in cryo-electron microscopy.
Journal of Structural Biology. 212(3), 107633.
mla: Fäßler, Florian, et al. “3D Printed Cell Culture Grid Holders for Improved
Cellular Specimen Preparation in Cryo-Electron Microscopy.” Journal of Structural
Biology, vol. 212, no. 3, 107633, Elsevier, 2020, doi:10.1016/j.jsb.2020.107633.
short: F. Fäßler, B. Zens, R. Hauschild, F.K. Schur, Journal of Structural Biology
212 (2020).
date_created: 2020-09-29T13:24:06Z
date_published: 2020-12-01T00:00:00Z
date_updated: 2024-03-28T23:30:05Z
day: '01'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1016/j.jsb.2020.107633
external_id:
isi:
- '000600997800008'
file:
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checksum: c48cbf594e84fc2f91966ffaafc0918c
content_type: application/pdf
creator: dernst
date_created: 2020-12-10T14:01:10Z
date_updated: 2020-12-10T14:01:10Z
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success: 1
file_date_updated: 2020-12-10T14:01:10Z
has_accepted_license: '1'
intvolume: ' 212'
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keyword:
- electron microscopy
- cryo-EM
- EM sample preparation
- 3D printing
- cell culture
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
grant_number: P33367
name: Structure and isoform diversity of the Arp2/3 complex
- _id: 059B463C-7A3F-11EA-A408-12923DDC885E
name: NÖ-Fonds Preis für die Jungforscherin des Jahres am IST Austria
publication: Journal of Structural Biology
publication_identifier:
issn:
- 1047-8477
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
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relation: used_in_publication
status: public
- id: '12491'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: 3D printed cell culture grid holders for improved cellular specimen preparation
in cryo-electron microscopy
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: 212
year: '2020'
...
---
_id: '8657'
abstract:
- lang: eng
text: "Synthesis of proteins – translation – is a fundamental process of life. Quantitative
studies anchor translation into the context of bacterial physiology and reveal
several mathematical relationships, called “growth laws,” which capture physiological
feedbacks between protein synthesis and cell growth. Growth laws describe the
dependency of the ribosome abundance as a function of growth rate, which can change
depending on the growth conditions. Perturbations of translation reveal that bacteria
employ a compensatory strategy in which the reduced translation capability results
in increased expression of the translation machinery.\r\nPerturbations of translation
are achieved in various ways; clinically interesting is the application of translation-targeting
antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology
are often poorly understood. Bacterial responses to two or more simultaneously
applied antibiotics are even more puzzling. The combined antibiotic effect determines
the type of drug interaction, which ranges from synergy (the effect is stronger
than expected) to antagonism (the effect is weaker) and suppression (one of the
drugs loses its potency).\r\nIn the first part of this work, we systematically
measure the pairwise interaction network for translation inhibitors that interfere
with different steps in translation. We find that the interactions are surprisingly
diverse and tend to be more antagonistic. To explore the underlying mechanisms,
we begin with a minimal biophysical model of combined antibiotic action. We base
this model on the kinetics of antibiotic uptake and binding together with the
physiological response described by the growth laws. The biophysical model explains
some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn
the second part of this work, we hypothesize that elusive suppressive drug interactions
result from the interplay between ribosomes halted in different stages of translation.
To elucidate this putative mechanism of drug interactions between translation
inhibitors, we generate translation bottlenecks genetically using in- ducible
control of translation factors that regulate well-defined translation cycle steps.
These perturbations accurately mimic antibiotic action and drug interactions,
supporting that the interplay of different translation bottlenecks partially causes
these interactions.\r\nWe extend this approach by varying two translation bottlenecks
simultaneously. This approach reveals the suppression of translocation inhibition
by inhibited translation. We rationalize this effect by modeling dense traffic
of ribosomes that move on transcripts in a translation factor-mediated manner.
This model predicts a dissolution of traffic jams caused by inhibited translocation
when the density of ribosome traffic is reduced by lowered initiation. We base
this model on the growth laws and quantitative relationships between different
translation and growth parameters.\r\nIn the final part of this work, we describe
a set of tools aimed at quantification of physiological and translation parameters.
We further develop a simple model that directly connects the abundance of a translation
factor with the growth rate, which allows us to extract physiological parameters
describing initiation. We demonstrate the development of tools for measuring translation
rate.\r\nThis thesis showcases how a combination of high-throughput growth rate
mea- surements, genetics, and modeling can reveal mechanisms of drug interactions.
Furthermore, by a gradual transition from combinations of antibiotics to precise
genetic interventions, we demonstrated the equivalency between genetic and chemi-
cal perturbations of translation. These findings tile the path for quantitative
studies of antibiotic combinations and illustrate future approaches towards the
quantitative description of translation."
acknowledged_ssus:
- _id: LifeSc
- _id: M-Shop
acknowledgement: I thank Life Science Facilities for their continuous support with
providing top-notch laboratory materials, keeping the devices humming, and coordinating
the repairs and building of custom-designed laboratory equipment with the MIBA Machine
shop.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
citation:
ama: 'Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics
and physiology. 2020. doi:10.15479/AT:ISTA:8657'
apa: 'Kavcic, B. (2020). Perturbations of protein synthesis: from antibiotics
to genetics and physiology. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8657'
chicago: 'Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to
Genetics and Physiology.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8657.'
ieee: 'B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics
and physiology,” Institute of Science and Technology Austria, 2020.'
ista: 'Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics
and physiology. Institute of Science and Technology Austria.'
mla: 'Kavcic, Bor. Perturbations of Protein Synthesis: From Antibiotics to Genetics
and Physiology. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8657.'
short: 'B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics
and Physiology, Institute of Science and Technology Austria, 2020.'
date_created: 2020-10-13T16:46:14Z
date_published: 2020-10-14T00:00:00Z
date_updated: 2023-09-07T13:20:48Z
day: '14'
ddc:
- '571'
- '530'
- '570'
degree_awarded: PhD
department:
- _id: GaTk
doi: 10.15479/AT:ISTA:8657
file:
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date_updated: 2021-10-07T22:30:03Z
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file_size: 321681247
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language:
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month: '10'
oa: 1
oa_version: Published Version
page: '271'
publication_identifier:
isbn:
- 978-3-99078-011-4
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7673'
relation: part_of_dissertation
status: public
- id: '8250'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
title: 'Perturbations of protein synthesis: from antibiotics to genetics and physiology'
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '7473'
abstract:
- lang: eng
text: How structural and functional properties of synapses relate to each other
is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms
of synaptic transmission, and electron microscopy (EM) has provided insight into
morphological properties of synapses. Here we describe an enhanced method for
functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure
freezing. We demonstrate that the improved method can be applied to intact networks
in acute brain slices and organotypic slice cultures from mice. As a proof of
concept, we probed vesicle pool changes during synaptic transmission at the hippocampal
mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked
vesicle pool and the functionally defined readily releasable pool and provide
evidence of fast endocytosis at this synapse. Functional EM with acute slices
and slice cultures has the potential to reveal the structural and functional mechanisms
of transmission in intact, genetically perturbed, and disease-affected synapses.
acknowledgement: This project has received funding from the European Research Council
(ERC) and European Commission (EC), under the European Union’s Horizon 2020 research
and innovation programme (ERC grant agreement No. 692692 and Marie Sklodowska-Curie
708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27
Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto
for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa
Zheden for extensive EM training, advice, and experimental assistance; Benjamin
Suter for substantial help with light stimulation, ImageJ plugins for analysis,
and manuscript editing; Florian Marr and Christina Altmutter for technical support;
Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger
(Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing
the Prox1-CreERT2 mouse line.
article_processing_charge: No
article_type: original
author:
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and
Freeze”) of identified cortical synapses in acute brain slices. Neuron.
2020;105:992-1006. doi:10.1016/j.neuron.2019.12.022
apa: Borges Merjane, C., Kim, O., & Jonas, P. M. (2020). Functional electron
microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain
slices. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2019.12.022
chicago: Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron
Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain
Slices.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2019.12.022.
ieee: C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy
(‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” Neuron,
vol. 105. Elsevier, pp. 992–1006, 2020.
ista: Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash
and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105,
992–1006.
mla: Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and
Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron,
vol. 105, Elsevier, 2020, pp. 992–1006, doi:10.1016/j.neuron.2019.12.022.
short: C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006.
date_created: 2020-02-10T15:59:45Z
date_published: 2020-03-18T00:00:00Z
date_updated: 2024-03-28T23:30:07Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.neuron.2019.12.022
ec_funded: 1
external_id:
isi:
- '000520854700008'
pmid:
- '31928842'
file:
- access_level: open_access
checksum: 3582664addf26859e86ac5bec3e01416
content_type: application/pdf
creator: dernst
date_created: 2020-11-20T08:58:53Z
date_updated: 2020-11-20T08:58:53Z
file_id: '8778'
file_name: 2020_Neuron_BorgesMerjane.pdf
file_size: 9712957
relation: main_file
success: 1
file_date_updated: 2020-11-20T08:58:53Z
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intvolume: ' 105'
isi: 1
language:
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month: '03'
oa: 1
oa_version: Published Version
page: 992-1006
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25BAF7B2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '708497'
name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal
mossy fiber synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 25C3DBB6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W01205
name: Zellkommunikation in Gesundheit und Krankheit
publication: Neuron
publication_identifier:
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/
record:
- id: '11196'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Functional electron microscopy (“Flash and Freeze”) of identified cortical
synapses in acute brain slices
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 105
year: '2020'
...
---
_id: '8250'
abstract:
- lang: eng
text: 'Antibiotics that interfere with translation, when combined, interact in diverse
and difficult-to-predict ways. Here, we explain these interactions by “translation
bottlenecks”: points in the translation cycle where antibiotics block ribosomal
progression. To elucidate the underlying mechanisms of drug interactions between
translation inhibitors, we generate translation bottlenecks genetically using
inducible control of translation factors that regulate well-defined translation
cycle steps. These perturbations accurately mimic antibiotic action and drug interactions,
supporting that the interplay of different translation bottlenecks causes these
interactions. We further show that growth laws, combined with drug uptake and
binding kinetics, enable the direct prediction of a large fraction of observed
interactions, yet fail to predict suppression. However, varying two translation
bottlenecks simultaneously supports that dense traffic of ribosomes and competition
for translation factors account for the previously unexplained suppression. These
results highlight the importance of “continuous epistasis” in bacterial physiology.'
acknowledgement: "We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K.
Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive
comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support,
which rendered this\r\nwork possible. B.K. thanks all members of Guet group for
many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges
the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work.
We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A.
Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This
work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P
27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to
T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.),
and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310
(to T.B.). Open access funding provided by\r\nProjekt DEAL."
article_number: '4013'
article_processing_charge: No
article_type: original
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between
translation-inhibiting antibiotics. Nature Communications. 2020;11. doi:10.1038/s41467-020-17734-z
apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). Mechanisms of drug
interactions between translation-inhibiting antibiotics. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-020-17734-z
chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of
Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications.
Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17734-z.
ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions
between translation-inhibiting antibiotics,” Nature Communications, vol.
11. Springer Nature, 2020.
ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between
translation-inhibiting antibiotics. Nature Communications. 11, 4013.
mla: Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting
Antibiotics.” Nature Communications, vol. 11, 4013, Springer Nature, 2020,
doi:10.1038/s41467-020-17734-z.
short: B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020).
date_created: 2020-08-12T09:13:50Z
date_published: 2020-08-11T00:00:00Z
date_updated: 2024-03-28T23:30:08Z
day: '11'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1038/s41467-020-17734-z
external_id:
isi:
- '000562769300008'
file:
- access_level: open_access
checksum: 986bebb308850a55850028d3d2b5b664
content_type: application/pdf
creator: dernst
date_created: 2020-08-17T07:36:57Z
date_updated: 2020-08-17T07:36:57Z
file_id: '8275'
file_name: 2020_NatureComm_Kavcic.pdf
file_size: 1965672
relation: main_file
success: 1
file_date_updated: 2020-08-17T07:36:57Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
record:
- id: '8657'
relation: dissertation_contains
status: public
status: public
title: Mechanisms of drug interactions between translation-inhibiting antibiotics
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2020'
...
---
_id: '7673'
abstract:
- lang: eng
text: Combining drugs can improve the efficacy of treatments. However, predicting
the effect of drug combinations is still challenging. The combined potency of
drugs determines the drug interaction, which is classified as synergistic, additive,
antagonistic, or suppressive. While probabilistic, non-mechanistic models exist,
there is currently no biophysical model that can predict antibiotic interactions.
Here, we present a physiologically relevant model of the combined action of antibiotics
that inhibit protein synthesis by targeting the ribosome. This model captures
the kinetics of antibiotic binding and transport, and uses bacterial growth laws
to predict growth in the presence of antibiotic combinations. We find that this
biophysical model can produce all drug interaction types except suppression. We
show analytically that antibiotics which cannot bind to the ribosome simultaneously
generally act as substitutes for one another, leading to additive drug interactions.
Previously proposed null expectations for higher-order drug interactions follow
as a limiting case of our model. We further extend the model to include the effects
of direct physical or allosteric interactions between individual drugs on the
ribosome. Notably, such direct interactions profoundly change the combined drug
effect, depending on the kinetic parameters of the drugs used. The model makes
additional predictions for the effects of resistance genes on drug interactions
and for interactions between ribosome-targeting antibiotics and antibiotics with
other targets. These findings enhance our understanding of the interplay between
drug action and cell physiology and are a key step toward a general framework
for predicting drug interactions.
article_processing_charge: No
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined
antibiotic action. bioRxiv. 2020. doi:10.1101/2020.04.18.047886
apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). A minimal biophysical
model of combined antibiotic action. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2020.04.18.047886
chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical
Model of Combined Antibiotic Action.” BioRxiv. Cold Spring Harbor Laboratory,
2020. https://doi.org/10.1101/2020.04.18.047886.
ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “A minimal biophysical model of
combined antibiotic action,” bioRxiv. Cold Spring Harbor Laboratory, 2020.
ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined
antibiotic action. bioRxiv, 10.1101/2020.04.18.047886.
mla: Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.”
BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.18.047886.
short: B. Kavcic, G. Tkačik, M.T. Bollenbach, BioRxiv (2020).
date_created: 2020-04-22T08:27:56Z
date_published: 2020-04-18T00:00:00Z
date_updated: 2024-03-28T23:30:08Z
day: '18'
department:
- _id: GaTk
doi: 10.1101/2020.04.18.047886
language:
- iso: eng
main_file_link:
- open_access: '1'
url: 'https://doi.org/10.1101/2020.04.18.047886 '
month: '04'
oa: 1
oa_version: Preprint
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: bioRxiv
publication_status: published
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '8997'
relation: later_version
status: public
- id: '8657'
relation: dissertation_contains
status: public
status: public
title: A minimal biophysical model of combined antibiotic action
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8002'
abstract:
- lang: eng
text: Wound healing in plant tissues, consisting of rigid cell wall-encapsulated
cells, represents a considerable challenge and occurs through largely unknown
mechanisms distinct from those in animals. Owing to their inability to migrate,
plant cells rely on targeted cell division and expansion to regenerate wounds.
Strict coordination of these wound-induced responses is essential to ensure efficient,
spatially restricted wound healing. Single-cell tracking by live imaging allowed
us to gain mechanistic insight into the wound perception and coordination of wound
responses after laser-based wounding in Arabidopsis root. We revealed a crucial
contribution of the collapse of damaged cells in wound perception and detected
an auxin increase specific to cells immediately adjacent to the wound. This localized
auxin increase balances wound-induced cell expansion and restorative division
rates in a dose-dependent manner, leading to tumorous overproliferation when the
canonical TIR1 auxin signaling is disrupted. Auxin and wound-induced turgor pressure
changes together also spatially define the activation of key components of regeneration,
such as the transcription regulator ERF115. Our observations suggest that the
wound signaling involves the sensing of collapse of damaged cells and a local
auxin signaling activation to coordinate the downstream transcriptional responses
in the immediate wound vicinity.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
article_number: '202003346'
article_processing_charge: No
article_type: original
author:
- first_name: Lukas
full_name: Hörmayer, Lukas
id: 2EEE7A2A-F248-11E8-B48F-1D18A9856A87
last_name: Hörmayer
orcid: 0000-0001-8295-2926
- first_name: Juan C
full_name: Montesinos López, Juan C
id: 310A8E3E-F248-11E8-B48F-1D18A9856A87
last_name: Montesinos López
orcid: 0000-0001-9179-6099
- first_name: Petra
full_name: Marhavá, Petra
id: 44E59624-F248-11E8-B48F-1D18A9856A87
last_name: Marhavá
- first_name: Eva
full_name: Benková, Eva
id: 38F4F166-F248-11E8-B48F-1D18A9856A87
last_name: Benková
orcid: 0000-0002-8510-9739
- first_name: Saiko
full_name: Yoshida, Saiko
id: 2E46069C-F248-11E8-B48F-1D18A9856A87
last_name: Yoshida
- first_name: Jiří
full_name: Friml, Jiří
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
citation:
ama: Hörmayer L, Montesinos López JC, Marhavá P, Benková E, Yoshida S, Friml J.
Wounding-induced changes in cellular pressure and localized auxin signalling spatially
coordinate restorative divisions in roots. Proceedings of the National Academy
of Sciences. 2020;117(26). doi:10.1073/pnas.2003346117
apa: Hörmayer, L., Montesinos López, J. C., Marhavá, P., Benková, E., Yoshida, S.,
& Friml, J. (2020). Wounding-induced changes in cellular pressure and localized
auxin signalling spatially coordinate restorative divisions in roots. Proceedings
of the National Academy of Sciences. Proceedings of the National Academy of
Sciences. https://doi.org/10.1073/pnas.2003346117
chicago: Hörmayer, Lukas, Juan C Montesinos López, Petra Marhavá, Eva Benková, Saiko
Yoshida, and Jiří Friml. “Wounding-Induced Changes in Cellular Pressure and Localized
Auxin Signalling Spatially Coordinate Restorative Divisions in Roots.” Proceedings
of the National Academy of Sciences. Proceedings of the National Academy of
Sciences, 2020. https://doi.org/10.1073/pnas.2003346117.
ieee: L. Hörmayer, J. C. Montesinos López, P. Marhavá, E. Benková, S. Yoshida, and
J. Friml, “Wounding-induced changes in cellular pressure and localized auxin signalling
spatially coordinate restorative divisions in roots,” Proceedings of the National
Academy of Sciences, vol. 117, no. 26. Proceedings of the National Academy
of Sciences, 2020.
ista: Hörmayer L, Montesinos López JC, Marhavá P, Benková E, Yoshida S, Friml J.
2020. Wounding-induced changes in cellular pressure and localized auxin signalling
spatially coordinate restorative divisions in roots. Proceedings of the National
Academy of Sciences. 117(26), 202003346.
mla: Hörmayer, Lukas, et al. “Wounding-Induced Changes in Cellular Pressure and
Localized Auxin Signalling Spatially Coordinate Restorative Divisions in Roots.”
Proceedings of the National Academy of Sciences, vol. 117, no. 26, 202003346,
Proceedings of the National Academy of Sciences, 2020, doi:10.1073/pnas.2003346117.
short: L. Hörmayer, J.C. Montesinos López, P. Marhavá, E. Benková, S. Yoshida, J.
Friml, Proceedings of the National Academy of Sciences 117 (2020).
date_created: 2020-06-22T13:33:52Z
date_published: 2020-06-30T00:00:00Z
date_updated: 2024-03-28T23:30:10Z
day: '30'
ddc:
- '580'
department:
- _id: JiFr
- _id: EvBe
doi: 10.1073/pnas.2003346117
ec_funded: 1
external_id:
isi:
- '000565729700033'
pmid:
- '32541049'
file:
- access_level: open_access
checksum: 908b09437680181de9990915f2113aca
content_type: application/pdf
creator: dernst
date_created: 2020-06-23T11:30:53Z
date_updated: 2020-07-14T12:48:07Z
file_id: '8009'
file_name: 2020_PNAS_Hoermayer.pdf
file_size: 2407102
relation: main_file
file_date_updated: 2020-07-14T12:48:07Z
has_accepted_license: '1'
intvolume: ' 117'
isi: 1
issue: '26'
language:
- iso: eng
month: '06'
oa: 1
oa_version: None
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: 262EF96E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29988
name: RNA-directed DNA methylation in plant development
publication: Proceedings of the National Academy of Sciences
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: Proceedings of the National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/how-wounded-plants-coordinate-their-healing/
record:
- id: '9992'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Wounding-induced changes in cellular pressure and localized auxin signalling
spatially coordinate restorative divisions in roots
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 117
year: '2020'
...
---
_id: '7680'
abstract:
- lang: eng
text: "Proteins and their complex dynamic interactions regulate cellular mechanisms
from sensing and transducing extracellular signals, to mediating genetic responses,
and sustaining or changing cell morphology. To manipulate these protein-protein
interactions (PPIs) that govern the behavior and fate of cells, synthetically
constructed, genetically encoded tools provide the means to precisely target proteins
of interest (POIs), and control their subcellular localization and activity in
vitro and in vivo. Ideal synthetic tools react to an orthogonal cue, i.e. a trigger
that does not activate any other endogenous process, thereby allowing manipulation
of the POI alone.\r\nIn optogenetics, naturally occurring photosensory domain
from plants, algae and bacteria are re-purposed and genetically fused to POIs.
Illumination with light of a specific wavelength triggers a conformational change
that can mediate PPIs, such as dimerization or oligomerization. By using light
as a trigger, these tools can be activated with high spatial and temporal precision,
on subcellular and millisecond scales. Chemogenetic tools consist of protein domains
that recognize and bind small molecules. By genetic fusion to POIs, these domains
can mediate PPIs upon addition of their specific ligands, which are often synthetically
designed to provide highly specific interactions and exhibit good bioavailability.\r\nMost
optogenetic tools to mediate PPIs are based on well-studied photoreceptors responding
to red, blue or near-UV light, leaving a striking gap in the green band of the
visible light spectrum. Among both optogenetic and chemogenetic tools, there is
an abundance of methods to induce PPIs, but tools to disrupt them require UV illumination,
rely on covalent linkage and subsequent enzymatic cleavage or initially result
in protein clustering of unknown stoichiometry.\r\nThis work describes how the
recently structurally and photochemically characterized green-light responsive
cobalamin-binding domains (CBDs) from bacterial transcription factors were re-purposed
to function as a green-light responsive optogenetic tool. In contrast to previously
engineered optogenetic tools, CBDs do not induce PPI, but rather confer a PPI
already upon expression, which can be rapidly disrupted by illumination. This
was employed to mimic inhibition of constitutive activity of a growth factor receptor,
and successfully implement for cell signalling in mammalian cells and in vivo
to rescue development in zebrafish. This work further describes the development
and application of a chemically induced de-dimerizer (CDD) based on a recently
identified and structurally described bacterial oxyreductase. CDD forms a dimer
upon expression in absence of its cofactor, the flavin derivative F420. Safety
and of domain expression and ligand exposure are demonstrated in vitro and in
vivo in zebrafish. The system is further applied to inhibit cell signalling output
from a chimeric receptor upon F420 treatment.\r\nCBDs and CDD expand the repertoire
of synthetic tools by providing novel mechanisms of mediating PPIs, and by recognizing
previously not utilized cues. In the future, they can readily be combined with
existing synthetic tools to functionally manipulate PPIs in vitro and in vivo."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Stephanie
full_name: Kainrath, Stephanie
id: 32CFBA64-F248-11E8-B48F-1D18A9856A87
last_name: Kainrath
citation:
ama: Kainrath S. Synthetic tools for optogenetic and chemogenetic inhibition of
cellular signals. 2020. doi:10.15479/AT:ISTA:7680
apa: Kainrath, S. (2020). Synthetic tools for optogenetic and chemogenetic inhibition
of cellular signals. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7680
chicago: Kainrath, Stephanie. “Synthetic Tools for Optogenetic and Chemogenetic
Inhibition of Cellular Signals.” Institute of Science and Technology Austria,
2020. https://doi.org/10.15479/AT:ISTA:7680.
ieee: S. Kainrath, “Synthetic tools for optogenetic and chemogenetic inhibition
of cellular signals,” Institute of Science and Technology Austria, 2020.
ista: Kainrath S. 2020. Synthetic tools for optogenetic and chemogenetic inhibition
of cellular signals. Institute of Science and Technology Austria.
mla: Kainrath, Stephanie. Synthetic Tools for Optogenetic and Chemogenetic Inhibition
of Cellular Signals. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7680.
short: S. Kainrath, Synthetic Tools for Optogenetic and Chemogenetic Inhibition
of Cellular Signals, Institute of Science and Technology Austria, 2020.
date_created: 2020-04-24T16:00:51Z
date_published: 2020-04-24T00:00:00Z
date_updated: 2023-09-22T09:20:10Z
day: '24'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:7680
file:
- access_level: open_access
checksum: fb9a4468eb27be92690728e35c823796
content_type: application/pdf
creator: stgingl
date_created: 2020-04-28T11:19:21Z
date_updated: 2021-10-31T23:30:05Z
embargo: 2021-10-30
file_id: '7692'
file_name: Thesis_without-signatures_PDFA.pdf
file_size: 3268017
relation: main_file
- access_level: closed
checksum: f6c80ca97104a631a328cb79a2c53493
content_type: application/octet-stream
creator: stgingl
date_created: 2020-04-28T11:19:24Z
date_updated: 2021-10-31T23:30:05Z
embargo_to: open_access
file_id: '7693'
file_name: Thesis_without signatures.docx
file_size: 5167703
relation: source_file
file_date_updated: 2021-10-31T23:30:05Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: None
page: '98'
publication_identifier:
eissn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '1028'
relation: dissertation_contains
status: public
status: public
supervisor:
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
title: Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '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.
date_created: 2020-10-07T14:53:13Z
date_published: 2020-10-12T00:00:00Z
date_updated: 2023-09-07T13:22:14Z
day: '12'
ddc:
- '610'
degree_awarded: PhD
department:
- _id: GaNo
doi: 10.15479/AT:ISTA:8620
file:
- access_level: open_access
checksum: 7ee83e42de3e5ce2fedb44dff472f75f
content_type: application/pdf
creator: jmorande
date_created: 2020-10-07T14:41:49Z
date_updated: 2021-10-16T22:30:04Z
embargo: 2021-10-15
file_id: '8621'
file_name: Jasmin_Morandell_Thesis-2020_final.pdf
file_size: 16155786
relation: main_file
- access_level: closed
checksum: 5e0464af453734210ce7aab7b4a92e3a
content_type: application/x-zip-compressed
creator: jmorande
date_created: 2020-10-07T14:45:07Z
date_updated: 2021-10-16T22:30:04Z
embargo_to: open_access
file_id: '8622'
file_name: Jasmin_Morandell_Thesis-2020_final.zip
file_size: 24344152
relation: source_file
file_date_updated: 2021-10-16T22:30:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '138'
project:
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F07807
name: 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:
- id: '7800'
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_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
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.
date_created: 2020-09-07T18:42:23Z
date_published: 2020-09-09T00:00:00Z
date_updated: 2023-09-07T13:26:17Z
day: '09'
ddc:
- '572'
degree_awarded: PhD
department:
- _id: LeSa
doi: 10.15479/AT:ISTA:8340
ec_funded: 1
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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: c635000d-4b10-11ee-a964-aac5a93f6ac1
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.).
date_created: 2020-05-05T14:31:33Z
date_published: 2020-01-11T00:00:00Z
date_updated: 2024-03-28T23:30:14Z
day: '11'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
- _id: LifeSc
doi: '10.1101/2020.01.10.902064 '
file:
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checksum: c6799ab5daba80efe8e2ed63c15f8c81
content_type: application/pdf
creator: rsix
date_created: 2020-05-05T14:31:19Z
date_updated: 2020-07-14T12:48:03Z
file_id: '7801'
file_name: 2020.01.10.902064v1.full.pdf
file_size: 2931370
relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Preprint
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '9429'
relation: later_version
status: public
- id: '8620'
relation: dissertation_contains
status: public
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
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
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.
date_created: 2020-07-19T22:00:58Z
date_published: 2020-12-01T00:00:00Z
date_updated: 2024-03-28T23:30:14Z
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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content_type: application/pdf
creator: dernst
date_created: 2020-07-22T06:47:45Z
date_updated: 2020-07-22T06:47:45Z
file_id: '8146'
file_name: 2020_CurrentOpGenetics_Basilico.pdf
file_size: 1381545
relation: main_file
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file_date_updated: 2020-07-22T06:47:45Z
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intvolume: ' 65'
isi: 1
issue: '12'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 126-137
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F07807
name: Neural stem cells in autism and epilepsy
publication: Current Opinion in Genetics and Development
publication_identifier:
eissn:
- '18790380'
issn:
- 0959437X
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '8620'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
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
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 65
year: '2020'
...
---
_id: '8434'
abstract:
- lang: eng
text: 'Efficient migration on adhesive surfaces involves the protrusion of lamellipodial
actin networks and their subsequent stabilization by nascent adhesions. The actin-binding
protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium
protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin
filaments and by interacting with the WAVE regulatory complex, an activator of
the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we
demonstrate that genetic ablation of Lpd compromises protrusion efficiency and
coincident cell migration without altering essential parameters of lamellipodia,
including their maximal rate of forward advancement and actin polymerization.
We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated
Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover,
computer-aided analysis of cell-edge morphodynamics on B16-F1 cell lamellipodia
revealed that loss of Lpd correlates with reduced temporal protrusion maintenance
as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes
protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction
and membrane ruffling.This article has an associated First Person interview with
the first author of the paper. '
acknowledgement: This work was supported in part by Deutsche Forschungsgemeinschaft
(DFG)[GRK2223/1, RO2414/5-1 (to K.R.), FA350/11-1 (to M.F.) and FA330/11-1 (to J.F.)],as
well as by intramural funding from the Helmholtz Association (to T.E.B.S. andK.R.).
G.D. was additionally funded by the Austrian Science Fund (FWF) LiseMeitner Program
[M-2495]. A.C.H. and M.W. are supported by the Francis CrickInstitute, which receives
its core funding from Cancer Research UK [FC001209], theMedical Research Council
[FC001209] and the Wellcome Trust [FC001209]. M.K. issupported by the Biotechnology
and Biological Sciences Research Council [BB/F011431/1, BB/J000590/1, BB/N000226/1].
Deposited in PMC for release after 6months.
article_number: jcs239020
article_processing_charge: No
article_type: original
author:
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Behnam
full_name: Amiri, Behnam
last_name: Amiri
- first_name: Ashley C.
full_name: Humphries, Ashley C.
last_name: Humphries
- first_name: Matthias
full_name: Schaks, Matthias
last_name: Schaks
- first_name: Vanessa
full_name: Dimchev, Vanessa
last_name: Dimchev
- first_name: Theresia E. B.
full_name: Stradal, Theresia E. B.
last_name: Stradal
- first_name: Jan
full_name: Faix, Jan
last_name: Faix
- first_name: Matthias
full_name: Krause, Matthias
last_name: Krause
- first_name: Michael
full_name: Way, Michael
last_name: Way
- first_name: Martin
full_name: Falcke, Martin
last_name: Falcke
- first_name: Klemens
full_name: Rottner, Klemens
last_name: Rottner
citation:
ama: Dimchev GA, Amiri B, Humphries AC, et al. Lamellipodin tunes cell migration
by stabilizing protrusions and promoting adhesion formation. Journal of Cell
Science. 2020;133(7). doi:10.1242/jcs.239020
apa: Dimchev, G. A., Amiri, B., Humphries, A. C., Schaks, M., Dimchev, V., Stradal,
T. E. B., … Rottner, K. (2020). Lamellipodin tunes cell migration by stabilizing
protrusions and promoting adhesion formation. Journal of Cell Science.
The Company of Biologists. https://doi.org/10.1242/jcs.239020
chicago: Dimchev, Georgi A, Behnam Amiri, Ashley C. Humphries, Matthias Schaks,
Vanessa Dimchev, Theresia E. B. Stradal, Jan Faix, et al. “Lamellipodin Tunes
Cell Migration by Stabilizing Protrusions and Promoting Adhesion Formation.” Journal
of Cell Science. The Company of Biologists, 2020. https://doi.org/10.1242/jcs.239020.
ieee: G. A. Dimchev et al., “Lamellipodin tunes cell migration by stabilizing
protrusions and promoting adhesion formation,” Journal of Cell Science,
vol. 133, no. 7. The Company of Biologists, 2020.
ista: Dimchev GA, Amiri B, Humphries AC, Schaks M, Dimchev V, Stradal TEB, Faix
J, Krause M, Way M, Falcke M, Rottner K. 2020. Lamellipodin tunes cell migration
by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science.
133(7), jcs239020.
mla: Dimchev, Georgi A., et al. “Lamellipodin Tunes Cell Migration by Stabilizing
Protrusions and Promoting Adhesion Formation.” Journal of Cell Science,
vol. 133, no. 7, jcs239020, The Company of Biologists, 2020, doi:10.1242/jcs.239020.
short: G.A. Dimchev, B. Amiri, A.C. Humphries, M. Schaks, V. Dimchev, T.E.B. Stradal,
J. Faix, M. Krause, M. Way, M. Falcke, K. Rottner, Journal of Cell Science 133
(2020).
date_created: 2020-09-17T14:00:33Z
date_published: 2020-04-09T00:00:00Z
date_updated: 2023-09-05T15:41:48Z
day: '09'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1242/jcs.239020
external_id:
isi:
- '000534387800005'
pmid:
- ' 32094266'
file:
- access_level: open_access
checksum: ba917e551acc4ece2884b751434df9ae
content_type: application/pdf
creator: dernst
date_created: 2020-09-17T14:07:51Z
date_updated: 2020-10-11T22:30:02Z
embargo: 2020-10-10
file_id: '8435'
file_name: 2020_JournalCellScience_Dimchev.pdf
file_size: 13493302
relation: main_file
file_date_updated: 2020-10-11T22:30:02Z
has_accepted_license: '1'
intvolume: ' 133'
isi: 1
issue: '7'
keyword:
- Cell Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2674F658-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02495
name: Protein structure and function in filopodia across scales
publication: Journal of Cell Science
publication_identifier:
eissn:
- 1477-9137
issn:
- 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
status: public
title: Lamellipodin tunes cell migration by stabilizing protrusions and promoting
adhesion formation
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 133
year: '2020'
...
---
_id: '7889'
abstract:
- lang: eng
text: Autoluminescent plants engineered to express a bacterial bioluminescence gene
cluster in plastids have not been widely adopted because of low light output.
We engineered tobacco plants with a fungal bioluminescence system that converts
caffeic acid (present in all plants) into luciferin and report self-sustained
luminescence that is visible to the naked eye. Our findings could underpin development
of a suite of imaging tools for plants.
acknowledgement: "This study was designed, performed and funded by Planta LLC. We
thank K. Wood for assisting in manuscript development. Planta acknowledges support
from the Skolkovo Innovation Centre. We thank D. Bolotin and the Milaboratory (milaboratory.com)
for access to computing and storage infrastructure. We thank S. Shakhov for providing\r\nphotography
equipment. The Synthetic Biology Group is funded by the MRC London Institute of
Medical Sciences (UKRI MC-A658-5QEA0, K.S.S.). K.S.S. is supported by an Imperial
College Research Fellowship. Experiments were partially carried out using equipment
provided by the Institute of Bioorganic Chemistry of the Russian Academy\r\nof Sciences
Сore Facility (CKP IBCH; supported by the Russian Ministry of Education and Science
Grant RFMEFI62117X0018). The F.A.K. lab is supported by ERC grant agreement 771209—CharFL.
This project received funding from the European Union’s Horizon 2020 Research and
Innovation Programme under Marie Skłodowska-Curie\r\nGrant Agreement 665385. K.S.S.
acknowledges support by President’s Grant 075-15-2019-411. Design and assembly of
some of the plasmids was supported by Russian Science Foundation grant 19-74-10102.
Imaging experiments were partially supported by Russian Science Foundation grant
17-14-01169p. LC-MS/MS analyses of extracts were\r\nsupported by Russian Science
Foundation grant 16-14-00052p. Design and assembly of plasmids was partially supported
by grant 075-15-2019-1789 from the Ministry of Science and Higher Education of the
Russian Federation allocated to the Center for Precision Genome Editing and Genetic
Technologies for Biomedicine. The authors\r\nwould like to acknowledge the work
of Genomics Core Facility of the Skolkovo Institute of Science and Technology, which
performed the sequencing and bioinformatic analysis."
article_processing_charge: No
article_type: original
author:
- first_name: Tatiana
full_name: Mitiouchkina, Tatiana
last_name: Mitiouchkina
- first_name: Alexander S.
full_name: Mishin, Alexander S.
last_name: Mishin
- first_name: Louisa
full_name: Gonzalez Somermeyer, Louisa
id: 4720D23C-F248-11E8-B48F-1D18A9856A87
last_name: Gonzalez Somermeyer
orcid: 0000-0001-9139-5383
- first_name: Nadezhda M.
full_name: Markina, Nadezhda M.
last_name: Markina
- first_name: Tatiana V.
full_name: Chepurnyh, Tatiana V.
last_name: Chepurnyh
- first_name: Elena B.
full_name: Guglya, Elena B.
last_name: Guglya
- first_name: Tatiana A.
full_name: Karataeva, Tatiana A.
last_name: Karataeva
- first_name: Kseniia A.
full_name: Palkina, Kseniia A.
last_name: Palkina
- first_name: Ekaterina S.
full_name: Shakhova, Ekaterina S.
last_name: Shakhova
- first_name: Liliia I.
full_name: Fakhranurova, Liliia I.
last_name: Fakhranurova
- first_name: Sofia V.
full_name: Chekova, Sofia V.
last_name: Chekova
- first_name: Aleksandra S.
full_name: Tsarkova, Aleksandra S.
last_name: Tsarkova
- first_name: Yaroslav V.
full_name: Golubev, Yaroslav V.
last_name: Golubev
- first_name: Vadim V.
full_name: Negrebetsky, Vadim V.
last_name: Negrebetsky
- first_name: Sergey A.
full_name: Dolgushin, Sergey A.
last_name: Dolgushin
- first_name: Pavel V.
full_name: Shalaev, Pavel V.
last_name: Shalaev
- first_name: Dmitry
full_name: Shlykov, Dmitry
last_name: Shlykov
- first_name: Olesya A.
full_name: Melnik, Olesya A.
last_name: Melnik
- first_name: Victoria O.
full_name: Shipunova, Victoria O.
last_name: Shipunova
- first_name: Sergey M.
full_name: Deyev, Sergey M.
last_name: Deyev
- first_name: Andrey I.
full_name: Bubyrev, Andrey I.
last_name: Bubyrev
- first_name: Alexander S.
full_name: Pushin, Alexander S.
last_name: Pushin
- first_name: Vladimir V.
full_name: Choob, Vladimir V.
last_name: Choob
- first_name: Sergey V.
full_name: Dolgov, Sergey V.
last_name: Dolgov
- first_name: Fyodor
full_name: Kondrashov, Fyodor
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
- first_name: Ilia V.
full_name: Yampolsky, Ilia V.
last_name: Yampolsky
- first_name: Karen S.
full_name: Sarkisyan, Karen S.
last_name: Sarkisyan
citation:
ama: Mitiouchkina T, Mishin AS, Gonzalez Somermeyer L, et al. Plants with genetically
encoded autoluminescence. Nature Biotechnology. 2020;38:944-946. doi:10.1038/s41587-020-0500-9
apa: Mitiouchkina, T., Mishin, A. S., Gonzalez Somermeyer, L., Markina, N. M., Chepurnyh,
T. V., Guglya, E. B., … Sarkisyan, K. S. (2020). Plants with genetically encoded
autoluminescence. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-020-0500-9
chicago: Mitiouchkina, Tatiana, Alexander S. Mishin, Louisa Gonzalez Somermeyer,
Nadezhda M. Markina, Tatiana V. Chepurnyh, Elena B. Guglya, Tatiana A. Karataeva,
et al. “Plants with Genetically Encoded Autoluminescence.” Nature Biotechnology.
Springer Nature, 2020. https://doi.org/10.1038/s41587-020-0500-9.
ieee: T. Mitiouchkina et al., “Plants with genetically encoded autoluminescence,”
Nature Biotechnology, vol. 38. Springer Nature, pp. 944–946, 2020.
ista: Mitiouchkina T, Mishin AS, Gonzalez Somermeyer L, Markina NM, Chepurnyh TV,
Guglya EB, Karataeva TA, Palkina KA, Shakhova ES, Fakhranurova LI, Chekova SV,
Tsarkova AS, Golubev YV, Negrebetsky VV, Dolgushin SA, Shalaev PV, Shlykov D,
Melnik OA, Shipunova VO, Deyev SM, Bubyrev AI, Pushin AS, Choob VV, Dolgov SV,
Kondrashov F, Yampolsky IV, Sarkisyan KS. 2020. Plants with genetically encoded
autoluminescence. Nature Biotechnology. 38, 944–946.
mla: Mitiouchkina, Tatiana, et al. “Plants with Genetically Encoded Autoluminescence.”
Nature Biotechnology, vol. 38, Springer Nature, 2020, pp. 944–46, doi:10.1038/s41587-020-0500-9.
short: T. Mitiouchkina, A.S. Mishin, L. Gonzalez Somermeyer, N.M. Markina, T.V.
Chepurnyh, E.B. Guglya, T.A. Karataeva, K.A. Palkina, E.S. Shakhova, L.I. Fakhranurova,
S.V. Chekova, A.S. Tsarkova, Y.V. Golubev, V.V. Negrebetsky, S.A. Dolgushin, P.V.
Shalaev, D. Shlykov, O.A. Melnik, V.O. Shipunova, S.M. Deyev, A.I. Bubyrev, A.S.
Pushin, V.V. Choob, S.V. Dolgov, F. Kondrashov, I.V. Yampolsky, K.S. Sarkisyan,
Nature Biotechnology 38 (2020) 944–946.
date_created: 2020-05-25T15:02:00Z
date_published: 2020-04-27T00:00:00Z
date_updated: 2023-09-05T15:30:34Z
day: '27'
ddc:
- '570'
department:
- _id: FyKo
doi: 10.1038/s41587-020-0500-9
ec_funded: 1
external_id:
isi:
- '000529298800003'
pmid:
- '32341562'
file:
- access_level: open_access
checksum: 1b30467500ec6277229a875b06e196d0
content_type: application/pdf
creator: dernst
date_created: 2020-08-28T08:57:07Z
date_updated: 2021-03-02T23:30:03Z
embargo: 2021-03-01
file_id: '8316'
file_name: 2020_NatureBiotech_Mitiouchkina.pdf
file_size: 1180086
relation: main_file
file_date_updated: 2021-03-02T23:30:03Z
has_accepted_license: '1'
intvolume: ' 38'
isi: 1
language:
- iso: eng
month: '04'
oa: 1
oa_version: Submitted Version
page: 944-946
pmid: 1
project:
- _id: 26580278-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '771209'
name: Characterizing the fitness landscape on population and global scales
publication: Nature Biotechnology
publication_identifier:
eissn:
- 1546-1696
issn:
- 1087-0156
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1038/s41587-020-0578-0
scopus_import: '1'
status: public
title: Plants with genetically encoded autoluminescence
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 38
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: 2024-03-28T23:30:19Z
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: '7426'
abstract:
- lang: eng
text: This paper presents a novel abstraction technique for analyzing Lyapunov and
asymptotic stability of polyhedral switched systems. A polyhedral switched system
is a hybrid system in which the continuous dynamics is specified by polyhedral
differential inclusions, the invariants and guards are specified by polyhedral
sets and the switching between the modes do not involve reset of variables. A
finite state weighted graph abstracting the polyhedral switched system is constructed
from a finite partition of the state–space, such that the satisfaction of certain
graph conditions, such as the absence of cycles with product of weights on the
edges greater than (or equal) to 1, implies the stability of the system. However,
the graph is in general conservative and hence, the violation of the graph conditions
does not imply instability. If the analysis fails to establish stability due to
the conservativeness in the approximation, a counterexample (cycle with product
of edge weights greater than or equal to 1) indicating a potential reason for
the failure is returned. Further, a more precise approximation of the switched
system can be constructed by considering a finer partition of the state–space
in the construction of the finite weighted graph. We present experimental results
on analyzing stability of switched systems using the above method.
article_number: '100856'
article_processing_charge: No
article_type: original
author:
- first_name: Miriam
full_name: Garcia Soto, Miriam
id: 4B3207F6-F248-11E8-B48F-1D18A9856A87
last_name: Garcia Soto
orcid: 0000−0003−2936−5719
- first_name: Pavithra
full_name: Prabhakar, Pavithra
last_name: Prabhakar
citation:
ama: 'Garcia Soto M, Prabhakar P. Abstraction based verification of stability of
polyhedral switched systems. Nonlinear Analysis: Hybrid Systems. 2020;36(5).
doi:10.1016/j.nahs.2020.100856'
apa: 'Garcia Soto, M., & Prabhakar, P. (2020). Abstraction based verification
of stability of polyhedral switched systems. Nonlinear Analysis: Hybrid Systems.
Elsevier. https://doi.org/10.1016/j.nahs.2020.100856'
chicago: 'Garcia Soto, Miriam, and Pavithra Prabhakar. “Abstraction Based Verification
of Stability of Polyhedral Switched Systems.” Nonlinear Analysis: Hybrid Systems.
Elsevier, 2020. https://doi.org/10.1016/j.nahs.2020.100856.'
ieee: 'M. Garcia Soto and P. Prabhakar, “Abstraction based verification of stability
of polyhedral switched systems,” Nonlinear Analysis: Hybrid Systems, vol.
36, no. 5. Elsevier, 2020.'
ista: 'Garcia Soto M, Prabhakar P. 2020. Abstraction based verification of stability
of polyhedral switched systems. Nonlinear Analysis: Hybrid Systems. 36(5), 100856.'
mla: 'Garcia Soto, Miriam, and Pavithra Prabhakar. “Abstraction Based Verification
of Stability of Polyhedral Switched Systems.” Nonlinear Analysis: Hybrid Systems,
vol. 36, no. 5, 100856, Elsevier, 2020, doi:10.1016/j.nahs.2020.100856.'
short: 'M. Garcia Soto, P. Prabhakar, Nonlinear Analysis: Hybrid Systems 36 (2020).'
date_created: 2020-02-02T23:00:59Z
date_published: 2020-05-01T00:00:00Z
date_updated: 2023-08-17T14:32:54Z
day: '01'
ddc:
- '000'
department:
- _id: ToHe
doi: 10.1016/j.nahs.2020.100856
external_id:
isi:
- '000528828600003'
file:
- access_level: open_access
checksum: 560abfddb53f9fe921b6744f59f2cfaa
content_type: application/pdf
creator: dernst
date_created: 2020-10-21T13:16:45Z
date_updated: 2022-05-16T22:30:04Z
embargo: 2022-05-15
file_id: '8688'
file_name: 2020_NAHS_GarciaSoto.pdf
file_size: 818774
relation: main_file
file_date_updated: 2022-05-16T22:30:04Z
has_accepted_license: '1'
intvolume: ' 36'
isi: 1
issue: '5'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Submitted Version
project:
- _id: 25863FF4-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: S11407
name: Game Theory
- _id: 25F42A32-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z211
name: The Wittgenstein Prize
publication: 'Nonlinear Analysis: Hybrid Systems'
publication_identifier:
issn:
- 1751-570X
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Abstraction based verification of stability of polyhedral switched systems
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 36
year: '2020'
...
---
_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.
date_created: 2020-12-30T15:41:26Z
date_published: 2020-12-30T00:00:00Z
date_updated: 2023-09-07T13:24:17Z
day: '30'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: DaSi
doi: 10.15479/AT:ISTA:8983
file:
- access_level: open_access
checksum: ec2797ab7a6f253b35df0572b36d1b43
content_type: application/pdf
creator: semtenan
date_created: 2020-12-30T15:34:01Z
date_updated: 2021-12-31T23:30:04Z
embargo: 2021-12-30
file_id: '8984'
file_name: Thesis_Shamsi_Emtenani_pdfA.pdf
file_size: 10848175
relation: main_file
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checksum: cc30e6608a9815414024cf548dff3b3a
content_type: application/pdf
creator: semtenan
date_created: 2020-12-30T15:37:36Z
date_updated: 2021-12-31T23:30:04Z
embargo_to: open_access
file_id: '8985'
file_name: Thesis_Shamsi_Emtenani_source file.pdf
file_size: 10073648
relation: source_file
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
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.).
date_created: 2020-09-23T09:36:47Z
date_published: 2020-09-18T00:00:00Z
date_updated: 2024-03-28T23:30:25Z
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: Drosophila TNFa´s Funktion in Immunzellen
- _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: Tissue barrier penetration is crucial for immunity and metastasis
publication: bioRxiv
publication_status: submitted
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'
...
---
_id: '8831'
abstract:
- lang: eng
text: Holes in planar Ge have high mobilities, strong spin-orbit interaction and
electrically tunable g-factors, and are therefore emerging as a promising candidate
for hybrid superconductorsemiconductor devices. This is further motivated by the
observation of supercurrent transport in planar Ge Josephson Field effect transistors
(JoFETs). A key challenge towards hybrid germanium quantum technology is the design
of high quality interfaces and superconducting contacts that are robust against
magnetic fields. By combining the assets of Al, which has a long superconducting
coherence, and Nb, which has a significant superconducting gap, we form low-disordered
JoFETs with large ICRN products that are capable of withstanding high magnetic
fields. We furthermore demonstrate the ability of phase-biasing individual JoFETs
opening up an avenue to explore topological superconductivity in planar Ge. The
persistence of superconductivity in the reported hybrid devices beyond 1.8 T paves
the way towards integrating spin qubits and proximity-induced superconductivity
on the same chip.
acknowledged_ssus:
- _id: M-Shop
- _id: NanoFab
acknowledgement: "This research and related results were made possible with the support
of the NOMIS Foundation. This research was supported by the Scientific Service Units
of IST Austria through resources provided by the MIBA Machine Shop and the nanofabrication
facility, the European Union’s Horizon 2020 research and innovation program under
the Marie Sklodowska-Curie grant agreement #844511 and the Grant Agreement #862046.
ICN2 acknowledge funding from Generalitat de Catalunya 2017 SGR 327. ICN2 is supported
by the Severo Ochoa\r\nprogram from Spanish MINECO (Grant No. SEV2017-0706) and
is funded by the CERCA Programme / Generalitat de Catalunya. Part of the present
work has been performed in the framework of Universitat Aut`onoma de Barcelona Materials
Science PhD program. The HAADF-STEM microscopy was conducted in the Laboratorio
de Microscopias Avanzadas at Instituto de Nanociencia de Aragon-Universidad de Zaragoza.
Authors acknowledge the LMA-INA for offering access to their instruments and expertise.
We acknowledge support from CSIC Research Platform on Quantum Technologies PTI-001.
This project has received funding from\r\nthe European Union’s Horizon 2020 research
and innovation programme under grant agreement No 823717 – ESTEEM3. M.B. acknowledges
support from SUR Generalitat de Catalunya and the EU Social Fund; project ref. 2020
FI 00103. GS and MV acknowledge support through a projectruimte grant associated
with the Netherlands Organization of Scientific Research (NWO)."
article_number: '2012.00322'
article_processing_charge: No
author:
- first_name: Kushagra
full_name: Aggarwal, Kushagra
id: b22ab905-3539-11eb-84c3-fc159dcd79cb
last_name: Aggarwal
orcid: 0000-0001-9985-9293
- first_name: Andrea C
full_name: Hofmann, Andrea C
id: 340F461A-F248-11E8-B48F-1D18A9856A87
last_name: Hofmann
- first_name: Daniel
full_name: Jirovec, Daniel
id: 4C473F58-F248-11E8-B48F-1D18A9856A87
last_name: Jirovec
orcid: 0000-0002-7197-4801
- first_name: Ivan
full_name: Prieto Gonzalez, Ivan
id: 2A307FE2-F248-11E8-B48F-1D18A9856A87
last_name: Prieto Gonzalez
orcid: 0000-0002-7370-5357
- first_name: Amir
full_name: Sammak, Amir
last_name: Sammak
- first_name: Marc
full_name: Botifoll, Marc
last_name: Botifoll
- first_name: Sara
full_name: Marti-Sanchez, Sara
last_name: Marti-Sanchez
- first_name: Menno
full_name: Veldhorst, Menno
last_name: Veldhorst
- first_name: Jordi
full_name: Arbiol, Jordi
last_name: Arbiol
- first_name: Giordano
full_name: Scappucci, Giordano
last_name: Scappucci
- first_name: Georgios
full_name: Katsaros, Georgios
id: 38DB5788-F248-11E8-B48F-1D18A9856A87
last_name: Katsaros
orcid: 0000-0001-8342-202X
citation:
ama: Aggarwal K, Hofmann AC, Jirovec D, et al. Enhancement of proximity induced
superconductivity in planar Germanium. arXiv.
apa: Aggarwal, K., Hofmann, A. C., Jirovec, D., Prieto Gonzalez, I., Sammak, A.,
Botifoll, M., … Katsaros, G. (n.d.). Enhancement of proximity induced superconductivity
in planar Germanium. arXiv.
chicago: Aggarwal, Kushagra, Andrea C Hofmann, Daniel Jirovec, Ivan Prieto Gonzalez,
Amir Sammak, Marc Botifoll, Sara Marti-Sanchez, et al. “Enhancement of Proximity
Induced Superconductivity in Planar Germanium.” ArXiv, n.d.
ieee: K. Aggarwal et al., “Enhancement of proximity induced superconductivity
in planar Germanium,” arXiv. .
ista: Aggarwal K, Hofmann AC, Jirovec D, Prieto Gonzalez I, Sammak A, Botifoll M,
Marti-Sanchez S, Veldhorst M, Arbiol J, Scappucci G, Katsaros G. Enhancement of
proximity induced superconductivity in planar Germanium. arXiv, 2012.00322.
mla: Aggarwal, Kushagra, et al. “Enhancement of Proximity Induced Superconductivity
in Planar Germanium.” ArXiv, 2012.00322.
short: K. Aggarwal, A.C. Hofmann, D. Jirovec, I. Prieto Gonzalez, A. Sammak, M.
Botifoll, S. Marti-Sanchez, M. Veldhorst, J. Arbiol, G. Scappucci, G. Katsaros,
ArXiv (n.d.).
date_created: 2020-12-02T10:42:53Z
date_published: 2020-12-02T00:00:00Z
date_updated: 2024-03-28T23:30:27Z
day: '02'
ddc:
- '530'
department:
- _id: GeKa
ec_funded: 1
external_id:
arxiv:
- '2012.00322'
file:
- access_level: open_access
checksum: 22a612e206232fa94b138b2c2f957582
content_type: application/pdf
creator: gkatsaro
date_created: 2020-12-02T10:42:31Z
date_updated: 2020-12-02T10:42:31Z
file_id: '8832'
file_name: Superconducting_2D_Ge.pdf
file_size: 1697939
relation: main_file
file_date_updated: 2020-12-02T10:42:31Z
has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Submitted Version
project:
- _id: 262116AA-B435-11E9-9278-68D0E5697425
name: Hybrid Semiconductor - Superconductor Quantum Devices
- _id: 26A151DA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '844511'
name: Majorana bound states in Ge/SiGe heterostructures
- _id: 237E5020-32DE-11EA-91FC-C7463DDC885E
call_identifier: H2020
grant_number: '862046'
name: TOPOLOGICALLY PROTECTED AND SCALABLE QUANTUM BITS
publication: arXiv
publication_status: submitted
related_material:
record:
- id: '10559'
relation: later_version
status: public
- id: '8834'
relation: research_data
status: public
- id: '10058'
relation: dissertation_contains
status: public
status: public
title: Enhancement of proximity induced superconductivity in planar Germanium
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8532'
abstract:
- lang: eng
text: The molecular anatomy of synapses defines their characteristics in transmission
and plasticity. Precise measurements of the number and distribution of synaptic
proteins are important for our understanding of synapse heterogeneity within and
between brain regions. Freeze–fracture replica immunogold electron microscopy
enables us to analyze them quantitatively on a two-dimensional membrane surface.
Here, we introduce Darea software, which utilizes deep learning for analysis of
replica images and demonstrate its usefulness for quick measurements of the pre-
and postsynaptic areas, density and distribution of gold particles at synapses
in a reproducible manner. We used Darea for comparing glutamate receptor and calcium
channel distributions between hippocampal CA3-CA1 spine synapses on apical and
basal dendrites, which differ in signaling pathways involved in synaptic plasticity.
We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic
size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA)
receptors with size. Interestingly, AMPA and NMDA receptors are segregated within
postsynaptic sites and negatively correlated in density among both apical and
basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels
show similar densities in apical and basal synapses with distributions consistent
with an exclusion zone model of calcium channel-release site topography.
acknowledgement: "This research was funded by Austrian Academy of Sciences, DOC fellowship
to D.K., European Research\r\nCouncil Advanced Grant 694539 and European Union Human
Brain Project (HBP) SGA2 785907 to R.S.\r\nWe acknowledge Elena Hollergschwandtner
for technical support."
article_number: '6737'
article_processing_charge: No
article_type: original
author:
- first_name: David
full_name: Kleindienst, David
id: 42E121A4-F248-11E8-B48F-1D18A9856A87
last_name: Kleindienst
- first_name: Jacqueline-Claire
full_name: Montanaro-Punzengruber, Jacqueline-Claire
id: 3786AB44-F248-11E8-B48F-1D18A9856A87
last_name: Montanaro-Punzengruber
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
- first_name: Matthew J
full_name: Case, Matthew J
id: 44B7CA5A-F248-11E8-B48F-1D18A9856A87
last_name: Case
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y,
Shigemoto R. Deep learning-assisted high-throughput analysis of freeze-fracture
replica images applied to glutamate receptors and calcium channels at hippocampal
synapses. International Journal of Molecular Sciences. 2020;21(18). doi:10.3390/ijms21186737
apa: Kleindienst, D., Montanaro-Punzengruber, J.-C., Bhandari, P., Case, M. J.,
Fukazawa, Y., & Shigemoto, R. (2020). Deep learning-assisted high-throughput
analysis of freeze-fracture replica images applied to glutamate receptors and
calcium channels at hippocampal synapses. International Journal of Molecular
Sciences. MDPI. https://doi.org/10.3390/ijms21186737
chicago: Kleindienst, David, Jacqueline-Claire Montanaro-Punzengruber, Pradeep Bhandari,
Matthew J Case, Yugo Fukazawa, and Ryuichi Shigemoto. “Deep Learning-Assisted
High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate
Receptors and Calcium Channels at Hippocampal Synapses.” International Journal
of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21186737.
ieee: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M. J. Case, Y.
Fukazawa, and R. Shigemoto, “Deep learning-assisted high-throughput analysis of
freeze-fracture replica images applied to glutamate receptors and calcium channels
at hippocampal synapses,” International Journal of Molecular Sciences,
vol. 21, no. 18. MDPI, 2020.
ista: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y,
Shigemoto R. 2020. Deep learning-assisted high-throughput analysis of freeze-fracture
replica images applied to glutamate receptors and calcium channels at hippocampal
synapses. International Journal of Molecular Sciences. 21(18), 6737.
mla: Kleindienst, David, et al. “Deep Learning-Assisted High-Throughput Analysis
of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels
at Hippocampal Synapses.” International Journal of Molecular Sciences,
vol. 21, no. 18, 6737, MDPI, 2020, doi:10.3390/ijms21186737.
short: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y.
Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020).
date_created: 2020-09-20T22:01:35Z
date_published: 2020-09-14T00:00:00Z
date_updated: 2024-03-28T23:30:31Z
day: '14'
ddc:
- '570'
department:
- _id: RySh
doi: 10.3390/ijms21186737
ec_funded: 1
external_id:
isi:
- '000579945300001'
file:
- access_level: open_access
checksum: 2e4f62f3cfe945b7391fc3070e5a289f
content_type: application/pdf
creator: dernst
date_created: 2020-09-21T14:08:58Z
date_updated: 2020-09-21T14:08:58Z
file_id: '8551'
file_name: 2020_JournMolecSciences_Kleindienst.pdf
file_size: 5748456
relation: main_file
success: 1
file_date_updated: 2020-09-21T14:08:58Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
issue: '18'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '694539'
name: 'In situ analysis of single channel subunit composition in neurons: physiological
implication in synaptic plasticity and behaviour'
- _id: 25D32BC0-B435-11E9-9278-68D0E5697425
name: Mechanism of formation and maintenance of input side-dependent asymmetry in
the hippocampus
- _id: 26436750-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '785907'
name: Human Brain Project Specific Grant Agreement 2 (HBP SGA 2)
publication: International Journal of Molecular Sciences
publication_identifier:
eissn:
- '14220067'
issn:
- '16616596'
publication_status: published
publisher: MDPI
quality_controlled: '1'
related_material:
record:
- id: '9562'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Deep learning-assisted high-throughput analysis of freeze-fracture replica
images applied to glutamate receptors and calcium channels at hippocampal synapses
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: 21
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
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name: 'ESOP: Programming Languages and Systems'
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title: Optimal and perfectly parallel algorithms for on-demand data-flow analysis
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...