---
_id: '17892'
abstract:
- lang: eng
text: "Enzyme-substrate kinetics form the basis of many biomolecular processes.
The interplay between substrate binding and substrate geometry can give rise to
long-range interactions between enzyme binding events. Here we study a general
model of enzyme-substrate kinetics with restricted long-range interactions described
by an exponent −\U0001D6FE. We employ a coherent-state path integral and renormalization
group approach to calculate the first moment and two-point correlation function
of the enzyme-binding profile. We show that starting from an empty substrate the
average occupancy follows a power law with an exponent 1/(1−\U0001D6FE) over time.
The correlation function decays algebraically with two distinct spatial regimes
characterized by exponents −\U0001D6FE on short distances and −(2/3)(2−\U0001D6FE)
on long distances. The crossover between both regimes scales inversely with the
average substrate occupancy. Our work allows associating experimental measurements
of bound enzyme locations with their binding kinetics and the spatial conformation
of the substrate."
acknowledgement: We thank F. Piazza, M. Henkel, and F. Jülicher for helpful feedback
and the entire Rulands group for fruitful discussions. We thank W. Reik, S. Clark,
T. Lohoff, and I. Kafetzopoulos for fruitful discussions about the biological aspects
of this work. This project has received funding from the European Research Council
(ERC) under the European Union's Horizon 2020 research and innovation program (Grant
No. 950349). This project has received funding from the European Union's Horizon
2020 research and innovation programme under the Marie Skłodowska-Curie Grant No.
101034413.
article_number: '024404'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Fabrizio
full_name: Olmeda, Fabrizio
id: 69dbf5fb-8a76-11ed-866b-fb486d8b5689
last_name: Olmeda
- first_name: Steffen
full_name: Rulands, Steffen
last_name: Rulands
citation:
ama: Olmeda F, Rulands S. Field theory of enzyme-substrate systems with restricted
long-range interactions. Physical Review E. 2024;110(2). doi:10.1103/PhysRevE.110.024404
apa: Olmeda, F., & Rulands, S. (2024). Field theory of enzyme-substrate systems
with restricted long-range interactions. Physical Review E. American Physical
Society. https://doi.org/10.1103/PhysRevE.110.024404
chicago: Olmeda, Fabrizio, and Steffen Rulands. “Field Theory of Enzyme-Substrate
Systems with Restricted Long-Range Interactions.” Physical Review E. American
Physical Society, 2024. https://doi.org/10.1103/PhysRevE.110.024404.
ieee: F. Olmeda and S. Rulands, “Field theory of enzyme-substrate systems with restricted
long-range interactions,” Physical Review E, vol. 110, no. 2. American
Physical Society, 2024.
ista: Olmeda F, Rulands S. 2024. Field theory of enzyme-substrate systems with restricted
long-range interactions. Physical Review E. 110(2), 024404.
mla: Olmeda, Fabrizio, and Steffen Rulands. “Field Theory of Enzyme-Substrate Systems
with Restricted Long-Range Interactions.” Physical Review E, vol. 110,
no. 2, 024404, American Physical Society, 2024, doi:10.1103/PhysRevE.110.024404.
short: F. Olmeda, S. Rulands, Physical Review E 110 (2024).
corr_author: '1'
das_tickbox: '0'
date_created: 2024-09-08T22:01:12Z
date_published: 2024-08-01T00:00:00Z
date_updated: 2026-10-01T10:06:45Z
day: '01'
ddc:
- '530'
department:
- _id: EdHa
doi: 10.1103/PhysRevE.110.024404
ec_funded: 1
external_id:
isi:
- '001299670100004'
pmid:
- '39294986'
file:
- access_level: open_access
checksum: 67fc2cc8eee3155e5c3b7380307d8284
content_type: application/pdf
creator: dernst
date_created: 2024-09-11T05:59:36Z
date_updated: 2024-09-11T05:59:36Z
file_id: '18053'
file_name: 2024_PhysReviewE_Olmeda.pdf
file_size: 445696
relation: main_file
success: 1
file_date_updated: 2024-09-11T05:59:36Z
fulldoi: https://doi.org/10.1103/PhysRevE.110.024404
has_accepted_license: '1'
intvolume: ' 110'
isi: 1
issue: '2'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: fc2ed2f7-9c52-11eb-aca3-c01059dda49c
call_identifier: H2020
grant_number: '101034413'
name: 'IST-BRIDGE: International postdoctoral program'
publication: Physical Review E
publication_identifier:
eissn:
- 2470-0053
issn:
- 2470-0045
publication_status: published
publisher: American Physical Society
quality_controlled: '1'
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: Field theory of enzyme-substrate systems with restricted long-range interactions
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 110
year: '2024'
...
---
_id: '17104'
abstract:
- lang: eng
text: 'The homeostasis of epithelial tissue relies on a balance between the self-renewal
of stem cell populations, cellular differentiation, and loss. Although this balance
needs to be tightly regulated to avoid pathologies, such as tumor growth, the
regulatory mechanisms, both cell-intrinsic and collective, which ensure tissue
steady-state are still poorly understood. Here, we develop a computational model
that incorporates basic assumptions of stem cell renewal into distinct populations
and mechanical interactions between cells. We find that the model generates unexpected
dynamic features: stem cells repel each other in the bulk tissue and are thus
found rather isolated, as in a number of in vivo contexts. By mapping the system
onto a gas of passive Brownian particles with effective repulsive interactions,
that arise from the generated flows of differentiated cells, we show that we can
quantitatively describe such stem cell distribution in tissues. The interaction
potential between a pair of stem cells decays exponentially with a characteristic
length that spans several cell sizes, corresponding to the volume of cells generated
per stem cell division. Our findings may help understanding the dynamics of normal
and cancerous epithelial tissues.'
acknowledgement: JE and JK gratefully acknowledge financial support from the Initiative
and Networking Fund (IVF) via the grant number ERC-RA-004. Simulations were performed
with computing resources granted by RWTH Aachen University under project ‘rwth0475’.
article_number: '097'
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Johannes C.
full_name: Krämer, Johannes C.
last_name: Krämer
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Gerhard
full_name: Gompper, Gerhard
last_name: Gompper
- first_name: Jens
full_name: Elgeti, Jens
last_name: Elgeti
citation:
ama: Krämer JC, Hannezo EB, Gompper G, Elgeti J. Mechanically-driven stem cell separation
in tissues caused by proliferating daughter cells. SciPost Physics. 2024;16(4).
doi:10.21468/scipostphys.16.4.097
apa: Krämer, J. C., Hannezo, E. B., Gompper, G., & Elgeti, J. (2024). Mechanically-driven
stem cell separation in tissues caused by proliferating daughter cells. SciPost
Physics. SciPost Foundation. https://doi.org/10.21468/scipostphys.16.4.097
chicago: Krämer, Johannes C., Edouard B Hannezo, Gerhard Gompper, and Jens Elgeti.
“Mechanically-Driven Stem Cell Separation in Tissues Caused by Proliferating Daughter
Cells.” SciPost Physics. SciPost Foundation, 2024. https://doi.org/10.21468/scipostphys.16.4.097.
ieee: J. C. Krämer, E. B. Hannezo, G. Gompper, and J. Elgeti, “Mechanically-driven
stem cell separation in tissues caused by proliferating daughter cells,” SciPost
Physics, vol. 16, no. 4. SciPost Foundation, 2024.
ista: Krämer JC, Hannezo EB, Gompper G, Elgeti J. 2024. Mechanically-driven stem
cell separation in tissues caused by proliferating daughter cells. SciPost Physics.
16(4), 097.
mla: Krämer, Johannes C., et al. “Mechanically-Driven Stem Cell Separation in Tissues
Caused by Proliferating Daughter Cells.” SciPost Physics, vol. 16, no.
4, 097, SciPost Foundation, 2024, doi:10.21468/scipostphys.16.4.097.
short: J.C. Krämer, E.B. Hannezo, G. Gompper, J. Elgeti, SciPost Physics 16 (2024).
das_tickbox: '1'
dataavailabilitystatement: Source code, simulation data, and analysis scripts will
be made publicly available on zenodo.org (10.5281/zenodo.8410957) after acceptance
of the manuscript.
date_created: 2024-06-03T08:58:44Z
date_published: 2024-04-08T00:00:00Z
date_updated: 2026-10-01T09:44:06Z
day: '08'
ddc:
- '530'
department:
- _id: EdHa
doi: 10.21468/scipostphys.16.4.097
external_id:
arxiv:
- '2310.04272'
isi:
- '001202370200001'
file:
- access_level: open_access
checksum: 6fdeecd21c166db8dedb927ecc2e6025
content_type: application/pdf
creator: dernst
date_created: 2024-06-03T11:18:51Z
date_updated: 2024-06-03T11:18:51Z
file_id: '17109'
file_name: 2024_SciPostPhys_Kraemer.pdf
file_size: 4973291
relation: main_file
success: 1
file_date_updated: 2024-06-03T11:18:51Z
fulldoi: https://doi.org/10.21468/scipostphys.16.4.097
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
publication: SciPost Physics
publication_identifier:
issn:
- 2542-4653
publication_status: published
publisher: SciPost Foundation
quality_controlled: '1'
related_material:
record:
- id: '23022'
relation: research_data
status: public
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Mechanically-driven stem cell separation in tissues caused by proliferating
daughter cells
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 16
year: '2024'
...
---
OA_type: closed access
_id: '18919'
abstract:
- lang: eng
text: The integration of theory and experiment makes possible tracking the slow
evolution of a photodoped Mott insulator to a distinct non-equilibrium metallic
phase under the influence of electron-lattice coupling.
article_processing_charge: No
article_type: letter_note
author:
- first_name: Denitsa Rangelova
full_name: Baykusheva, Denitsa Rangelova
id: 71b4d059-2a03-11ee-914d-dfa3beed6530
last_name: Baykusheva
orcid: 0000-0002-7438-1139
citation:
ama: Baykusheva DR. Through the slopes of a light-induced phase transition. Nature
Physics. 2024;20(5):684-685. doi:10.1038/s41567-024-02401-7
apa: Baykusheva, D. R. (2024). Through the slopes of a light-induced phase transition.
Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-024-02401-7
chicago: Baykusheva, Denitsa Rangelova. “Through the Slopes of a Light-Induced Phase
Transition.” Nature Physics. Springer Nature, 2024. https://doi.org/10.1038/s41567-024-02401-7.
ieee: D. R. Baykusheva, “Through the slopes of a light-induced phase transition,”
Nature Physics, vol. 20, no. 5. Springer Nature, pp. 684–685, 2024.
ista: Baykusheva DR. 2024. Through the slopes of a light-induced phase transition.
Nature Physics. 20(5), 684–685.
mla: Baykusheva, Denitsa Rangelova. “Through the Slopes of a Light-Induced Phase
Transition.” Nature Physics, vol. 20, no. 5, Springer Nature, 2024, pp.
684–85, doi:10.1038/s41567-024-02401-7.
short: D.R. Baykusheva, Nature Physics 20 (2024) 684–685.
corr_author: '1'
das_tickbox: '0'
date_created: 2025-01-27T14:29:20Z
date_published: 2024-05-01T00:00:00Z
date_updated: 2026-10-01T09:37:00Z
day: '01'
department:
- _id: DeBa
doi: 10.1038/s41567-024-02401-7
external_id:
isi:
- '001162208200002'
fulldoi: https://doi.org/10.1038/s41567-024-02401-7
intvolume: ' 20'
isi: 1
issue: '5'
language:
- iso: eng
month: '05'
oa_version: None
page: 684-685
publication: Nature Physics
publication_identifier:
eissn:
- 1745-2481
issn:
- 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: Through the slopes of a light-induced phase transition
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 20
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '23022'
abstract:
- lang: eng
text: "Contains animations, data, and source code used for the paper \"Mechanically-driven
Stem Cell Separation in Tissues caused by Proliferating Daughter Cells\" by the
same authors. \r\n\r\n\r\nThis repository contains all the data and analysis scripts
to support the manuscript\r\nThe file structure is as follows:\r\n- \"analysis\"
contains all the analysis scripts\r\n- \"gfx\" and \"animations\" the figures
and supporting animations\r\n- \"1-SCpair\", \"2-SCtissue\", \"3-BDsimulation\",
\"4-tissue-stochdiv\", \"6-inertia-effects\" all the source code and data for
the respective models."
article_processing_charge: No
author:
- first_name: Jens
full_name: Elgeti, Jens
last_name: Elgeti
- first_name: Johannes
full_name: Krämer, Johannes
last_name: Krämer
citation:
ama: Elgeti J, Krämer J. Data for Mechanically-driven Stem Cell Separation in Tissues
caused by Proliferating Daughter Cells. 2024. doi:10.5281/zenodo.8410956
apa: Elgeti, J., & Krämer, J. (2024). Data for Mechanically-driven Stem Cell
Separation in Tissues caused by Proliferating Daughter Cells. Zenodo. https://doi.org/10.5281/zenodo.8410956
chicago: Elgeti, Jens, and Johannes Krämer. “Data for Mechanically-Driven Stem Cell
Separation in Tissues Caused by Proliferating Daughter Cells.” Zenodo, 2024. https://doi.org/10.5281/zenodo.8410956.
ieee: J. Elgeti and J. Krämer, “Data for Mechanically-driven Stem Cell Separation
in Tissues caused by Proliferating Daughter Cells.” Zenodo, 2024.
ista: Elgeti J, Krämer J. 2024. Data for Mechanically-driven Stem Cell Separation
in Tissues caused by Proliferating Daughter Cells, Zenodo, 10.5281/zenodo.8410956.
mla: Elgeti, Jens, and Johannes Krämer. Data for Mechanically-Driven Stem Cell
Separation in Tissues Caused by Proliferating Daughter Cells. Zenodo, 2024,
doi:10.5281/zenodo.8410956.
short: J. Elgeti, J. Krämer, (2024).
date_created: 2026-10-01T09:44:01Z
date_published: 2024-03-25T00:00:00Z
date_updated: 2026-10-01T09:44:07Z
day: '25'
ddc:
- '530'
department:
- _id: EdHa
doi: 10.5281/zenodo.8410956
fulldoi: https://doi.org/10.5281/zenodo.8410956
main_file_link:
- open_access: '1'
url: https://doi.org/10.5281/zenodo.8410956
month: '03'
oa: 1
oa_version: None
publisher: Zenodo
related_material:
record:
- id: '17104'
relation: used_in_publication
status: public
status: public
title: Data for Mechanically-driven Stem Cell Separation in Tissues caused by Proliferating
Daughter Cells
type: research_data_reference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
APC_amount: 2570,79 EUR
OA_place: publisher
OA_type: hybrid
_id: '17123'
abstract:
- lang: eng
text: A key feature of many developmental systems is their ability to self-organize
spatial patterns of functionally distinct cell fates. To ensure proper biological
function, such patterns must be established reproducibly, by controlling and even
harnessing intrinsic and extrinsic fluctuations. While the relevant molecular
processes are increasingly well understood, we lack a principled framework to
quantify the performance of such stochastic self-organizing systems. To that end,
we introduce an information-theoretic measure for self-organized fate specification
during embryonic development. We show that the proposed measure assesses the total
information content of fate patterns and decomposes it into interpretable contributions
corresponding to the positional and correlational information. By optimizing the
proposed measure, our framework provides a normative theory for developmental
circuits, which we demonstrate on lateral inhibition, cell type proportioning,
and reaction–diffusion models of self-organization. This paves a way toward a
classification of developmental systems based on a common information-theoretic
language, thereby organizing the zoo of implicated chemical and mechanical signaling
processes.
acknowledgement: We thank Wiktor Młynarski, Juraj Majek, Michal Hledík, Fridtjof Brauns,
Nikolas Claussen, Benjamin Zoller, Erwin Frey, Thomas Gregor, and Edouard Hannezo
for inspiring discussions. D.B.B. was supported by the NOMIS foundation as a NOMIS
Fellow and by an European Molecular Biology Organization (EMBO) Postdoctoral Fellowship
(ALTF 343-2022). This research was performed in part at the Aspen Center for Physics,
which is supported by NSF Grant No. PHY-1607611, and Kavli Institute for Theoretical
Physics (KITP) Santa Barbara, supported by NSF Grant No. PHY-1748958 and the Gordon
and Betty Moore Foundation Grant No. 2919.02.
article_number: e2322326121
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: David
full_name: Brückner, David
id: e1e86031-6537-11eb-953a-f7ab92be508d
last_name: Brückner
orcid: 0000-0001-7205-2975
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Brückner D, Tkačik G. Information content and optimization of self-organized
developmental systems. Proceedings of the National Academy of Sciences of the
United States of America. 2024;121(23). doi:10.1073/pnas.2322326121
apa: Brückner, D., & Tkačik, G. (2024). Information content and optimization
of self-organized developmental systems. Proceedings of the National Academy
of Sciences of the United States of America. National Academy of Sciences.
https://doi.org/10.1073/pnas.2322326121
chicago: Brückner, David, and Gašper Tkačik. “Information Content and Optimization
of Self-Organized Developmental Systems.” Proceedings of the National Academy
of Sciences of the United States of America. National Academy of Sciences,
2024. https://doi.org/10.1073/pnas.2322326121.
ieee: D. Brückner and G. Tkačik, “Information content and optimization of self-organized
developmental systems,” Proceedings of the National Academy of Sciences of
the United States of America, vol. 121, no. 23. National Academy of Sciences,
2024.
ista: Brückner D, Tkačik G. 2024. Information content and optimization of self-organized
developmental systems. Proceedings of the National Academy of Sciences of the
United States of America. 121(23), e2322326121.
mla: Brückner, David, and Gašper Tkačik. “Information Content and Optimization of
Self-Organized Developmental Systems.” Proceedings of the National Academy
of Sciences of the United States of America, vol. 121, no. 23, e2322326121,
National Academy of Sciences, 2024, doi:10.1073/pnas.2322326121.
short: D. Brückner, G. Tkačik, Proceedings of the National Academy of Sciences of
the United States of America 121 (2024).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: There were no data generated as part of this study. Code
to perform simulations, evaluate entropy and information quantities, and optimize
parameters is available at https://github.com/dbrueckner/SelforgInformation (90).
date_created: 2024-06-09T22:01:02Z
date_published: 2024-06-04T00:00:00Z
date_updated: 2026-10-01T11:03:59Z
day: '04'
ddc:
- '570'
department:
- _id: EdHa
- _id: GaTk
doi: 10.1073/pnas.2322326121
external_id:
isi:
- '001244835000006'
pmid:
- '38819997'
file:
- access_level: open_access
checksum: 59797a75db7beb3721ed7a4d14c241f9
content_type: application/pdf
creator: dernst
date_created: 2024-06-10T10:27:37Z
date_updated: 2024-06-10T10:27:37Z
file_id: '17130'
file_name: 2024_PNAS_Brueckner.pdf
file_size: 12329234
relation: main_file
success: 1
file_date_updated: 2024-06-10T10:27:37Z
fulldoi: https://doi.org/10.1073/pnas.2322326121
has_accepted_license: '1'
intvolume: ' 121'
isi: 1
issue: '23'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 34e2a5b5-11ca-11ed-8bc3-b2265616ef0b
grant_number: ALTF 343-2022
name: A mechano-chemical theory for stem cell fate decisions in organoid development
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/dbrueckner/SelforgInformation
- description: News on the ISTA website
relation: press_release
url: https://ista.ac.at/en/news/the-embryo-assembles-itself/
researchdata_availability: not applicable
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Information content and optimization of self-organized developmental 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 121
year: '2024'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '17885'
abstract:
- lang: eng
text: 'The formation of new ribosomes is tightly coordinated with cell growth and
proliferation. In eukaryotes, the correct assembly of all ribosomal proteins and
RNAs follows an intricate scheme of maturation and rearrangement steps across
three cellular compartments: the nucleolus, nucleoplasm, and cytoplasm. We demonstrate
that usnic acid, a lichen secondary metabolite, inhibits the maturation of the
large ribosomal subunit in yeast. We combine biochemical characterization of pre-ribosomal
particles with a quantitative single-particle cryo-EM approach to monitor changes
in nucleolar particle populations upon drug treatment. Usnic acid rapidly blocks
the transition from nucleolar state B to C of Nsa1-associated pre-ribosomes, depleting
key maturation factors such as Dbp10 and hindering pre-rRNA processing. This primary
nucleolar block rapidly rebounds on earlier stages of the pathway which highlights
the regulatory linkages between different steps. In summary, we provide an in-depth
characterization of the effect of usnic acid on ribosome biogenesis, which may
have implications for its reported anti-cancer activities.'
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: We thank Michael A. McAlear, Micheline Fromont-Racin, Philipp Milkereit,
Arlen W. Johnson, Sabine Rospert, Ed Hurt, C. Yam, Günter Daum, Wolfgang Zachariae,
Katrin Karbstein, Juan P. G. Ballesta, Mercedes Dosil, Miguel Remacha und Jesus
de la Cruz for sharing strains or providing antibodies. We thank the members of
the Bergler lab and the Haselbach lab for their helpful discussion. We thank Ellen
Zhong for helpful discussions about the quantitative cryoDRGN analysis. This research
was supported by the Scientific Service Units of IST Austria through resources provided
by the Electron Microscopy Facility. This research was funded in whole, or in part,
by the Austrian Science Foundation grants [https://doi.org/10.55776/P32977], [https://doi.org/10.55776/P29451]
and [https://doi.org/10.55776/P32536] (to H.B.). Research at the IMP is generously
supported by Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter
grant FFG-852936). For the purpose of open access, the author has applied a CC BY
public copyright licence to any Author Accepted Manuscript version arising from
this submission.
article_number: '7511'
article_processing_charge: Yes
article_type: original
author:
- first_name: Lisa
full_name: Kofler, Lisa
last_name: Kofler
- first_name: Lorenz
full_name: Grundmann, Lorenz
last_name: Grundmann
- first_name: Magdalena
full_name: Gerhalter, Magdalena
last_name: Gerhalter
- first_name: Michael
full_name: Prattes, Michael
last_name: Prattes
- first_name: Juliane
full_name: Merl-Pham, Juliane
last_name: Merl-Pham
- first_name: Gertrude
full_name: Zisser, Gertrude
last_name: Zisser
- first_name: Irina
full_name: Grishkovskaya, Irina
last_name: Grishkovskaya
- first_name: Victor-Valentin
full_name: Hodirnau, Victor-Valentin
id: 3661B498-F248-11E8-B48F-1D18A9856A87
last_name: Hodirnau
orcid: 0000-0003-3904-947X
- first_name: Martin
full_name: Vareka, Martin
last_name: Vareka
- first_name: Rolf
full_name: Breinbauer, Rolf
last_name: Breinbauer
- first_name: Stefanie M.
full_name: Hauck, Stefanie M.
last_name: Hauck
- first_name: David
full_name: Haselbach, David
last_name: Haselbach
- first_name: Helmut
full_name: Bergler, Helmut
last_name: Bergler
citation:
ama: Kofler L, Grundmann L, Gerhalter M, et al. The novel ribosome biogenesis inhibitor
usnic acid blocks nucleolar pre-60S maturation. Nature Communications.
2024;15. doi:10.1038/s41467-024-51754-3
apa: Kofler, L., Grundmann, L., Gerhalter, M., Prattes, M., Merl-Pham, J., Zisser,
G., … Bergler, H. (2024). The novel ribosome biogenesis inhibitor usnic acid blocks
nucleolar pre-60S maturation. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-024-51754-3
chicago: Kofler, Lisa, Lorenz Grundmann, Magdalena Gerhalter, Michael Prattes, Juliane
Merl-Pham, Gertrude Zisser, Irina Grishkovskaya, et al. “The Novel Ribosome Biogenesis
Inhibitor Usnic Acid Blocks Nucleolar Pre-60S Maturation.” Nature Communications.
Springer Nature, 2024. https://doi.org/10.1038/s41467-024-51754-3.
ieee: L. Kofler et al., “The novel ribosome biogenesis inhibitor usnic acid
blocks nucleolar pre-60S maturation,” Nature Communications, vol. 15. Springer
Nature, 2024.
ista: Kofler L, Grundmann L, Gerhalter M, Prattes M, Merl-Pham J, Zisser G, Grishkovskaya
I, Hodirnau V-V, Vareka M, Breinbauer R, Hauck SM, Haselbach D, Bergler H. 2024.
The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation.
Nature Communications. 15, 7511.
mla: Kofler, Lisa, et al. “The Novel Ribosome Biogenesis Inhibitor Usnic Acid Blocks
Nucleolar Pre-60S Maturation.” Nature Communications, vol. 15, 7511, Springer
Nature, 2024, doi:10.1038/s41467-024-51754-3.
short: L. Kofler, L. Grundmann, M. Gerhalter, M. Prattes, J. Merl-Pham, G. Zisser,
I. Grishkovskaya, V.-V. Hodirnau, M. Vareka, R. Breinbauer, S.M. Hauck, D. Haselbach,
H. Bergler, Nature Communications 15 (2024).
das_tickbox: '1'
dataavailabilitystatement: Strains generated in this study are available from the
corresponding authors upon request. For cryo-EM model building, published pre-60S
models PDB-6EM3, PDB-6EM4, PDB-6C0F, PDB-6EM1 and PDB-8V87 were used. Motion-corrected
micrographs with annotated particle locations were deposited in EMPIAR with the
accession number EMPIAR-12237. The cryo-EM maps of clusters 1 to 4 with the combined
datasets were deposited in the EMDB with the accession numbers EMD-51122, EMD-51126,
EMD-51128, and EMD-51129. The reconstructions for the treated dataset were deposited
with the accession numbers EMD-51175, EMD-51176, EMD-51177, and EMD-51178, while
the untreated reconstructions of reported clusters can be found via EMD-51164, EMD-51165,
EMD-51166, EMD-51167. The mass spectrometry proteomics data have been deposited
to the ProteomeXchange Consortium via the PRIDE101 partner repository with the dataset
identifier PXD046691. Source data are provided with this paper.
date_created: 2024-09-08T22:01:10Z
date_published: 2024-08-29T00:00:00Z
date_updated: 2026-10-01T11:05:46Z
day: '29'
ddc:
- '570'
department:
- _id: EM-Fac
doi: 10.1038/s41467-024-51754-3
external_id:
isi:
- '001457895200001'
pmid:
- '39209816'
file:
- access_level: open_access
checksum: 7c044538a47182c826d1b526c52958a2
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creator: dernst
date_created: 2024-09-09T08:56:12Z
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relation: main_file
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file_date_updated: 2024-09-09T08:56:12Z
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has_accepted_license: '1'
intvolume: ' 15'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S
maturation
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 15
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '23023'
abstract:
- lang: eng
text: "In this repository, you will find the R-scripts used to generate the figures,
along with the data necessary to make the plots. You will also find the Python-scripts
used to compute the pair-wise distance between embryos, to estimate the surface,
the volume, the α-parameter, to identify the closest rigid packing and to generate
the morphomap. Additionally, you have access to the base model used with Plantseg
to predict and label the cells at the 8-cell stage. Note that a more accurate
and more specific model was generated for each embryo based on the curation of
at least 5 timepoints.\r\n\r\nFigures\r\nThe plots in Figure 1-7 and Figure S1-S7
can be generated with the respective files. The code is written in R and requires
RStudio to work out-of-the-box. The R scripts are located in figures/. Figures
and supplemental figures are generated with the same file (e.g., Figure 1.R generates
all the computed panels of Figure 1 and Figure S1). Data required to generate
the plots are located in figures/data/. Note that the code to work with the morphomap
and the tracking data is located in local packages figures/fabreges.morphomap
and figures/fabreges.tracking. An additional package figures/fabreges.generic
contains utility functions.\r\n\r\nPython packages\r\nFor the needs of this study,
we developed a series of package for Python located in python-packages/. The packages
can be directly imported within your scripts. Along with the packages, you will
find 6 scripts used to compute, extract or estimate the data from the source.
The folder is organised as follow:\r\n\r\npackage interfaces is located in python-packages/interfaces/
and can be tested by running the scripts to extract the angles an estimate the
surface of contact (compute-angles.py and estimate-contacts.py respectively) in
folder python-packages,\r\npackage morphomap is located in python-packages/morphomap/
and can be tested by running the script to compute the geometrical distances between
embryos, project the data in 2D and compute the volume of the cells (compute-distances.py,
process-distances.py and compute-volumes.py respectively) in folder python-packages,\r\npackage
splinefit is included in morphomap in python-packages/morphomap/splinefit/, but
can function independently,\r\npackage rbb is located in python-packages/rbb/
and can be tested by running the script to identify the closest rigid packing
of an embryo at the 8-cell stage (identify-packing.py) in folder python-packages.\r\nWe
provide example of segmented data in python-packages/samples/.\r\n\r\nCNN\r\nWe
provide a convolutional neural network (CNN) used in our study, located in cnn.
Please note that we optimised the CNN further for each dataset by doing manual
curation of at least 5 time points and by retraining the network with those ground
truth. The CNN were trained using pytorch-3dunet. The CNN can be used with Plantseg.
Currently (plantseg v.1.6.0 and pytorch-3dunet v.1.6.0), the output model from
pytorch-3dunet must currently be modified to work with plantseg:\r\n\r\n# python\r\nimport
torch\r\nfor model in ('best_checkpoint.pytorch', 'last_checkpoint.pytorch'):\r\n
\ state = torch.load(model, map_location='cpu')\r\n state = state['model_state_dict']\r\n
\ torch.save(state, model)\r\n\r\nRequierements\r\nFigures\r\nThe figures were
generated with R (v. 4.4.0) and RStudio (v. 2024.04.1+748). The following packages
must be installed prior to execution:\r\n\r\nalphashape3d (v. 1.3.2)\r\ndevtools
(v. 2.4.5)\r\nggplot2 (v. 3.5.1)\r\nggrepel (v. 0.9.5)\r\nrstudioapi (v. 0.16.0)\r\nTo
install all these packages, run the following command in the RStudio console:\r\n\r\n#
R\r\ninstall.packages(c(\"alphashape3d@1.3.2\", \"devtools@2.4.5\", \"ggplot2@3.5.1\",
\"ggrepel@0.9.5\", \"rstudioapi@0.16\"))\r\n\r\nMore recent version of R, RStudio
and the packages may also work (not tested).\r\n\r\nPython packages\r\nPython
3.12.3 was used to analyse the data. The scripts may work with more recent version
of Python and with Python 3.8 or earlier (not tested). To run the code, you must
first install the following packages:\r\n\r\nnumpy (v. 1.26.4)\r\nimageio (v.
2.34.1)\r\nscipy (v. 1.13.1)\r\nscikit-image (v. 0.23.2)\r\nscikit-learn (v. 1.5.0)\r\nAlternatively,
you can create a conda environment:\r\n\r\n# Shell script\r\nconda create -y --name
fabreges2024 python=3.12.3\r\nconda activate fabreges2024\r\npython -m pip install
numpy==1.26.4 imageio==2.34.1 scipy==1.13.1 scikit-image==0.23.2 scikit-learn==1.5.0\r\n\r\nMore
recent version of the dependencies may work (not tested).\r\n\r\nUsage\r\nFigures\r\nOpen
one of the figure script in RStudio and run the entire code. You may have to create
a folder output in figures/ if it does not exist.\r\n\r\nThe code has local dependencies
that will be installed on your computer when encountering them for the first time.
They start with fabreges.* and are necessary to generate the figures.\r\n\r\nPython
packages (example)\r\nCompute angles\r\n# Shell script\r\n# Compute a summary
(mean, median, s.d.) of the angles in embryo C1 at time 40\r\npython compute-angles.py
-s -r 15 -R 20 samples/C1_t040.tif.gz output/C1_t040_angles.csv\r\n# Compute a
detailed list of angle values\r\npython compute-angles.py -r 15 -R 20 samples/C1_t041.tif.gz
output/C1_t041_angles.csv\r\n\r\nCompute distances\r\n# Shell script\r\n# Compute
the distance between two embryos\r\npython compute-distances.py -c 5 -s 5 samples/C1_t040.tif.gz
samples/C1_t041.tif.gz output/distances.csv\r\n# Append another distance measurement\r\npython
compute-distances.py -a -c 5 -s 5 samples/C1_t040.tif.gz samples/C1_t042.tif.gz
output/distances.csv\r\n\r\nCompute volumes\r\n# Shell script\r\n# Compute the
volume in isotropic data\r\npython compute-volumes.py -r 0.416 0.416 0.416 samples/C1_t040.tif.gz
output/volumes.csv\r\n\r\nEstimate contacts\r\n# Shell script\r\n# Estimate the
contacts and the free surface area\r\npython estimate-contacts.py -r 0.416 0.416
0.416 samples/C1_t040.tif.gz output/contacts.csv\r\n\r\nIdentify the closest rigid
packing\r\n# Shell script\r\n# Assuming the file `output/contacts.csv` exists
and contains the output\r\n# from command `estimate-contacts.py`.\r\n# Identify
the closest rigid packings\r\npython identify-packing.py output/contacts.csv output/backbones.csv\r\n\r\nGenerate
the seeds for Surface Evolver\r\n# Shell script\r\n# Assuming the file `output/contacts.csv`
exists and contains the output\r\n# from command `estimate-contacts.py`, and the
file `output/volumes.csv`\r\n# exists and contains the output from command `compute-volumes.py`\r\n#
Generate the seeds for Surface Evolver using automatic thresholding\r\n# Automatic
threshold will determine the highest cell-cell contact threshold\r\n# that preserves
rigidity of the embryo (or 0 if not rigid)\r\npython generate-seed.py output/contacts.csv
output/volumes.csv output/seed.fe\r\n# Generate the seeds for Surface Evolver
with custom threshold\r\npython generate-seed.py --threshold 0.1 output/contacts.csv
output/volumes.csv output/seed.fe\r\n\r\nProject in 2D and generate a distance
matrix\r\n# Shell script\r\n# Assuming the folder `foo` only contains one or more
CSV\r\n# from command `compute-distances.py`.\r\n\r\n# Compute the tSNE 2D projection\r\npython
process-distances.py -D2 -t output/tsne_2d.csv foo/\r\n\r\n# Compute the tSNE
3D projection\r\npython process-distances.py -D3 -t output/tsne_2d.csv foo/\r\n\r\n#
Generate the distance matrix\r\npython process-distances.py -m output/dismat.csv
foo/"
article_processing_charge: No
author:
- first_name: Bernat
full_name: Corominas-Murtra, Bernat
last_name: Corominas-Murtra
- first_name: Prachiti
full_name: ' Moghe, Prachiti'
last_name: ' Moghe'
- first_name: Alison
full_name: Kickuth, Alison
last_name: Kickuth
- first_name: Takafumi
full_name: Ichikawa, Takafumi
last_name: Ichikawa
- first_name: Chizuru
full_name: Iwatani, Chizuru
last_name: Iwatani
- first_name: Tomoyuki
full_name: Tsukiyama, Tomoyuki
last_name: Tsukiyama
- first_name: Nathalie
full_name: Daniel, Nathalie
last_name: Daniel
- first_name: Julie
full_name: Gering, Julie
last_name: Gering
- first_name: Anniek
full_name: Stokkermans, Anniek
last_name: Stokkermans
- first_name: Adrian
full_name: Wolny, Adrian
last_name: Wolny
- first_name: Anna
full_name: Kreshuk, Anna
last_name: Kreshuk
- first_name: Véronique
full_name: Duranthon, Véronique
last_name: Duranthon
- first_name: Virginie
full_name: Uhlmann, Virginie
last_name: Uhlmann
- first_name: Edouard
full_name: Hannezo, Edouard
last_name: Hannezo
- first_name: Takashi
full_name: Hiiragi, Takashi
last_name: Hiiragi
citation:
ama: 'Corominas-Murtra B, Moghe P, Kickuth A, et al. Data and software from: Temporal
variability and cell mechanics control robustness in mammalian embryogenesis.
2024. doi:10.5281/zenodo.12819780'
apa: 'Corominas-Murtra, B., Moghe, P., Kickuth, A., Ichikawa, T., Iwatani, C.,
Tsukiyama, T., … Hiiragi, T. (2024). Data and software from: Temporal variability
and cell mechanics control robustness in mammalian embryogenesis. Institute of
Science and Technology Austria. https://doi.org/10.5281/zenodo.12819780'
chicago: 'Corominas-Murtra, Bernat, Prachiti Moghe, Alison Kickuth, Takafumi Ichikawa,
Chizuru Iwatani, Tomoyuki Tsukiyama, Nathalie Daniel, et al. “Data and Software
from: Temporal Variability and Cell Mechanics Control Robustness in Mammalian
Embryogenesis.” Institute of Science and Technology Austria, 2024. https://doi.org/10.5281/zenodo.12819780.'
ieee: 'B. Corominas-Murtra et al., “Data and software from: Temporal variability
and cell mechanics control robustness in mammalian embryogenesis.” Institute of
Science and Technology Austria, 2024.'
ista: 'Corominas-Murtra B, Moghe P, Kickuth A, Ichikawa T, Iwatani C, Tsukiyama
T, Daniel N, Gering J, Stokkermans A, Wolny A, Kreshuk A, Duranthon V, Uhlmann
V, Hannezo E, Hiiragi T. 2024. Data and software from: Temporal variability and
cell mechanics control robustness in mammalian embryogenesis, Institute of Science
and Technology Austria, 10.5281/zenodo.12819780.'
mla: 'Corominas-Murtra, Bernat, et al. Data and Software from: Temporal Variability
and Cell Mechanics Control Robustness in Mammalian Embryogenesis. Institute
of Science and Technology Austria, 2024, doi:10.5281/zenodo.12819780.'
short: B. Corominas-Murtra, P. Moghe, A. Kickuth, T. Ichikawa, C. Iwatani, T.
Tsukiyama, N. Daniel, J. Gering, A. Stokkermans, A. Wolny, A. Kreshuk, V. Duranthon,
V. Uhlmann, E. Hannezo, T. Hiiragi, (2024).
contributor:
- contributor_type: contact_person
first_name: Dimitri
last_name: Fabrèges
date_created: 2026-10-01T10:54:27Z
date_published: 2024-07-25T00:00:00Z
date_updated: 2026-10-01T10:54:33Z
day: '25'
department:
- _id: EdHa
doi: 10.5281/zenodo.12819780
fulldoi: https://doi.org/10.5281/zenodo.12819780
main_file_link:
- open_access: '1'
url: https://doi.org/10.5281/zenodo.12819780
month: '07'
oa: 1
oa_version: None
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '18446'
relation: used_in_publication
status: public
status: public
title: 'Data and software from: Temporal variability and cell mechanics control robustness
in mammalian embryogenesis'
type: research_data_reference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
_id: '18913'
abstract:
- lang: eng
text: "With the proliferation of blockchain technology in high-value sectors, consensus
protocols are becoming critical infrastructures. The rapid innovation cycle in
Byzantine fault tolerant (BFT) consensus protocols has culminated in HotStuff,
which provides linear message complexity in the partially synchronous setting.
To achieve this, HotStuff leverages a leader that collects, aggregates, and broadcasts
the messages of other validators. This paper analyzes the security implications
of such approaches in practice, from the perspective of liveness and availability.\r\nBy
implementing attacks in a globally-distributed testbed, we show that state-of-the-art
leader-based protocols are vulnerable to denial-of-service (DoS) attacks on the
leader. Our attacks, demonstrated on committees of up to 64 validators, manage
to disrupt liveness within seconds, using only a few tens of Mbps of attack bandwidth
per validator. Crucially, the cost and effectiveness of the attacks are independent
of the committee size. Based on the outcome of these experiments, we then propose
and test effective mitigations. Our findings show that advancements in both protocol
design and network-layer defenses can greatly improve the practical resilience
of BFT consensus protocols."
acknowledgement: This work was mostly realized while Alberto Sonnino and Lefteris
Kokoris-Kogias were employed at Meta. We gratefully acknowledge support for this
project from ETH Zurich and Mysten Labs.
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Giacomo
full_name: Giuliari, Giacomo
last_name: Giuliari
- first_name: Alberto
full_name: Sonnino, Alberto
last_name: Sonnino
- first_name: Marc
full_name: Frei, Marc
last_name: Frei
- first_name: Fabio
full_name: Streun, Fabio
last_name: Streun
- first_name: Eleftherios
full_name: Kokoris Kogias, Eleftherios
id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
last_name: Kokoris Kogias
orcid: 0000-0002-8827-3382
- first_name: Adrian
full_name: Perrig, Adrian
last_name: Perrig
citation:
ama: 'Giuliari G, Sonnino A, Frei M, Streun F, Kokoris Kogias E, Perrig A. An empirical
study of consensus protocols’ DoS resilience. In: Proceedings of the 19th ACM
Asia Conference on Computer and Communications Security. ACM; 2024:1345-1360.
doi:10.1145/3634737.3656997'
apa: 'Giuliari, G., Sonnino, A., Frei, M., Streun, F., Kokoris Kogias, E., &
Perrig, A. (2024). An empirical study of consensus protocols’ DoS resilience.
In Proceedings of the 19th ACM Asia Conference on Computer and Communications
Security (pp. 1345–1360). Singapore, Singapore: ACM. https://doi.org/10.1145/3634737.3656997'
chicago: Giuliari, Giacomo, Alberto Sonnino, Marc Frei, Fabio Streun, Eleftherios
Kokoris Kogias, and Adrian Perrig. “An Empirical Study of Consensus Protocols’
DoS Resilience.” In Proceedings of the 19th ACM Asia Conference on Computer
and Communications Security, 1345–60. ACM, 2024. https://doi.org/10.1145/3634737.3656997.
ieee: G. Giuliari, A. Sonnino, M. Frei, F. Streun, E. Kokoris Kogias, and A. Perrig,
“An empirical study of consensus protocols’ DoS resilience,” in Proceedings
of the 19th ACM Asia Conference on Computer and Communications Security, Singapore,
Singapore, 2024, pp. 1345–1360.
ista: 'Giuliari G, Sonnino A, Frei M, Streun F, Kokoris Kogias E, Perrig A. 2024.
An empirical study of consensus protocols’ DoS resilience. Proceedings of the
19th ACM Asia Conference on Computer and Communications Security. ASIACCS: Asia
Conference on Computer and Communications Security, 1345–1360.'
mla: Giuliari, Giacomo, et al. “An Empirical Study of Consensus Protocols’ DoS Resilience.”
Proceedings of the 19th ACM Asia Conference on Computer and Communications
Security, ACM, 2024, pp. 1345–60, doi:10.1145/3634737.3656997.
short: G. Giuliari, A. Sonnino, M. Frei, F. Streun, E. Kokoris Kogias, A. Perrig,
in:, Proceedings of the 19th ACM Asia Conference on Computer and Communications
Security, ACM, 2024, pp. 1345–1360.
conference:
end_date: 2024-07-05
location: Singapore, Singapore
name: 'ASIACCS: Asia Conference on Computer and Communications Security'
start_date: 2024-07-01
das_tickbox: '0'
date_created: 2025-01-27T13:57:00Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2026-10-01T11:04:34Z
day: '01'
ddc:
- '000'
department:
- _id: ElKo
doi: 10.1145/3634737.3656997
external_id:
isi:
- '001283918100095'
file:
- access_level: open_access
checksum: 1e743ddf49d35390eb56e11eb0759150
content_type: application/pdf
creator: dernst
date_created: 2025-01-27T14:04:12Z
date_updated: 2025-01-27T14:04:12Z
file_id: '18914'
file_name: 2024_ACMAsiaCCS_Giuliari.pdf
file_size: 951940
relation: main_file
success: 1
file_date_updated: 2025-01-27T14:04:12Z
fulldoi: https://doi.org/10.1145/3634737.3656997
has_accepted_license: '1'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1345-1360
publication: Proceedings of the 19th ACM Asia Conference on Computer and Communications
Security
publication_identifier:
isbn:
- '9798400704826'
publication_status: published
publisher: ACM
quality_controlled: '1'
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: An empirical study of consensus protocols’ DoS resilience
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
OA_place: repository
OA_type: hybrid
_id: '18957'
abstract:
- lang: eng
text: Sui Lutris is the first smart-contract platform to sustainably achieve sub-second
finality. It achieves this significant decrease by employing consensusless agreement
not only for simple payments but for a large variety of transactions. Unlike prior
work, Sui Lutris neither compromises expressiveness nor throughput and can run
perpetually without restarts. Sui Lutris achieves this by safely integrating consensuless
agreement with a high-throughput consensus protocol that is invoked out of the
critical finality path but ensures that when a transaction is at risk of inconsistent
concurrent accesses, its settlement is delayed until the total ordering is resolved.
Building such a hybrid architecture is especially delicate during reconfiguration
events, where the system needs to preserve the safety of the consensusless path
without compromising the long-term liveness of potentially misconfigured clients.
We thus develop a novel reconfiguration protocol, the first to provably show the
safe and efficient reconfiguration of a consensusless blockchain. Sui Lutris is
currently running in production and underpins the Sui smart-contract platform.
Combined with the use of Objects instead of accounts it enables the safe execution
of smart contracts that expose objects as a first-class resource. In our experiments
Sui Lutris achieves latency lower than 0.5 seconds for throughput up to 5,000
certificates per second (150k ops/s with transaction blocks), compared to the
state-of-the-art real-world consensus latencies of 3 seconds. Furthermore, it
gracefully handles validators crash-recovery and does not suffer visible performance
degradation during reconfiguration.
acknowledgement: 'This work is funded by MystenLabs. We thank the Mysten Labs Engineering
teams for valuable feedback broadly, and specifically Dmitry Perelman and Todd Fiala
for managing the implementation effort. A number of folks contributed to specific
aspects of the implementation of Sui Lutris (amongst many other contributions to
the overall blockchain): Francois Garillot, Laura Makdah, Mingwei Tian, Andrew Schran,
Sadhan Sood and William Smith implemented and optimized aspects of both Sui Lutris
and Narwhal / Bullshark consensus; Alonso de Gortari oversaw the cryptoeconomics
of the blockchain, and Emma Zhong, Ade Adepoju, Tim Zakia and Dario Russi designed
and implemented staking and gas mechanisms. Adam Welc designed several Move tools
and provided great feedback on the manuscript. We also extend our thanks to Patrick
Kuo, Ge Gao, Chris Li, and Arun Koshy for their work on the Sui Lutris SDK, clients,
and RPC layer; Kostas Chalkias, Jonas Lindstrøm, and Joy Wang built cryptographic
components.'
article_processing_charge: No
arxiv: 1
author:
- first_name: Sam
full_name: Blackshear, Sam
last_name: Blackshear
- first_name: Andrey
full_name: Chursin, Andrey
last_name: Chursin
- first_name: George
full_name: Danezis, George
last_name: Danezis
- first_name: Anastasios
full_name: Kichidis, Anastasios
last_name: Kichidis
- first_name: Eleftherios
full_name: Kokoris Kogias, Eleftherios
id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
last_name: Kokoris Kogias
orcid: 0000-0002-8827-3382
- first_name: Xun
full_name: Li, Xun
last_name: Li
- first_name: Mark
full_name: Logan, Mark
last_name: Logan
- first_name: Ashok
full_name: Menon, Ashok
last_name: Menon
- first_name: Todd
full_name: Nowacki, Todd
last_name: Nowacki
- first_name: Alberto
full_name: Sonnino, Alberto
last_name: Sonnino
- first_name: Brandon
full_name: Williams, Brandon
last_name: Williams
- first_name: Lu
full_name: Zhang, Lu
last_name: Zhang
citation:
ama: 'Blackshear S, Chursin A, Danezis G, et al. Sui Lutris: A blockchain combining
broadcast and consensus. In: Proceedings of the 2024 on ACM SIGSAC Conference
on Computer and Communications Security. ACM; 2024:2606-2620. doi:10.1145/3658644.3670286'
apa: 'Blackshear, S., Chursin, A., Danezis, G., Kichidis, A., Kokoris Kogias, E.,
Li, X., … Zhang, L. (2024). Sui Lutris: A blockchain combining broadcast and consensus.
In Proceedings of the 2024 on ACM SIGSAC Conference on Computer and Communications
Security (pp. 2606–2620). Salt Lake City, UT, United States: ACM. https://doi.org/10.1145/3658644.3670286'
chicago: 'Blackshear, Sam, Andrey Chursin, George Danezis, Anastasios Kichidis,
Eleftherios Kokoris Kogias, Xun Li, Mark Logan, et al. “Sui Lutris: A Blockchain
Combining Broadcast and Consensus.” In Proceedings of the 2024 on ACM SIGSAC
Conference on Computer and Communications Security, 2606–20. ACM, 2024. https://doi.org/10.1145/3658644.3670286.'
ieee: 'S. Blackshear et al., “Sui Lutris: A blockchain combining broadcast
and consensus,” in Proceedings of the 2024 on ACM SIGSAC Conference on Computer
and Communications Security, Salt Lake City, UT, United States, 2024, pp.
2606–2620.'
ista: 'Blackshear S, Chursin A, Danezis G, Kichidis A, Kokoris Kogias E, Li X, Logan
M, Menon A, Nowacki T, Sonnino A, Williams B, Zhang L. 2024. Sui Lutris: A blockchain
combining broadcast and consensus. Proceedings of the 2024 on ACM SIGSAC Conference
on Computer and Communications Security. CCS: Conference on Computer and Communications
Security, 2606–2620.'
mla: 'Blackshear, Sam, et al. “Sui Lutris: A Blockchain Combining Broadcast and
Consensus.” Proceedings of the 2024 on ACM SIGSAC Conference on Computer and
Communications Security, ACM, 2024, pp. 2606–20, doi:10.1145/3658644.3670286.'
short: S. Blackshear, A. Chursin, G. Danezis, A. Kichidis, E. Kokoris Kogias, X.
Li, M. Logan, A. Menon, T. Nowacki, A. Sonnino, B. Williams, L. Zhang, in:, Proceedings
of the 2024 on ACM SIGSAC Conference on Computer and Communications Security,
ACM, 2024, pp. 2606–2620.
conference:
end_date: 2024-10-18
location: Salt Lake City, UT, United States
name: 'CCS: Conference on Computer and Communications Security'
start_date: 2024-10-14
das_tickbox: '0'
date_created: 2025-01-29T12:42:21Z
date_published: 2024-12-09T00:00:00Z
date_updated: 2026-10-01T11:04:52Z
day: '09'
department:
- _id: ElKo
doi: 10.1145/3658644.3670286
external_id:
arxiv:
- '2310.18042'
isi:
- '001436367300178'
fulldoi: https://doi.org/10.1145/3658644.3670286
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.48550/arXiv.2310.18042
month: '12'
oa: 1
oa_version: Preprint
page: 2606-2620
publication: Proceedings of the 2024 on ACM SIGSAC Conference on Computer and Communications
Security
publication_identifier:
isbn:
- '9798400706363'
publication_status: published
publisher: ACM
quality_controlled: '1'
researchdata_availability: no
status: public
supplementarymaterial: no
title: 'Sui Lutris: A blockchain combining broadcast and consensus'
type: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '17269'
abstract:
- lang: eng
text: The directed migration of epithelial cell collectives through coordinated
movements plays a crucial role in various physiological processes and is increasingly
understood at the level of large confluent monolayers. However, numerous processes
rely on the migration of small groups of polarized epithelial clusters in complex
environments, and their responses to external geometries remain poorly understood.
To address this, we cultivate primary epithelial keratocyte tissues on adhesive
microstripes to create autonomous epithelial clusters with well-defined geometries.
We show that their migration efficiency is strongly influenced by the contact
geometry and the orientation of cell–cell contacts with respect to the direction
of migration. A combination of velocity and polarity alignment with contact regulation
of locomotion in an active matter model captures quantitatively the experimental
data. Furthermore, we predict that this combination of rules enables efficient
navigation in complex geometries, which we confirm experimentally. Altogether,
our findings provide a conceptual framework for extracting the interaction rules
of active systems from their interaction with physical boundaries, as well as
design principles for collective navigation in complex microenvironments.
acknowledgement: M.L., E.V. and S.G. acknowledge funding from the European Regional
Development Fund (ERDF) Prostem Research Project (No. 1510614, Wallonia DG06), the
Epiforce Project of the National Fund for Scientific Research, Belgium (FRS-FNRS;
Project No. T.0092.21), the Cellsqueezer Project of FRS-FNRS (Project No. J.0061.23),
the Optopattern Project of FRS-FNRS (Project no. U.NO26.22) and the Interreg MAT(T)ISSE
project, which is financially supported by Interreg France-Wallonie-Vlaanderen,
ERDF). A.R. and M.L. are financially supported by FRS-FNRS as a research fellow
(Aspirant FNRS) and Postdoctoral Researcher (Chargée de Recherches FNRS), respectively.
E.V. and Y.K. are financially supported by FRS-FNRS through grants from the Fund
for Research Training in Industry and Agriculture (FRIA). This project was supported
by the European Research Council under the European Union’s Horizon 2020 Research
and Innovation Programme (Grant Agreement No. 851288 to E.H.) and Marie Skłodowska-Curie
Actions (Grant Agreement No. 797621 to M.G.-G.). D.B.B. was supported by the NOMIS
foundation as a NOMIS fellow and by the European Molecular Biology Organization
(Postdoctoral Fellowship ALTF 343-2022) and performed this work in part at the Aspen
Center for Physics, which is supported by the National Science Foundation (Grant
No. PHY-1607611). X.T. and M.G.-G. acknowledge support from the Government of Catalonia
(Grant No. AGAUR SGR-2017-01602 and a CERCA Programme), the Spanish Ministry for
Science and Innovation and ERDF (Grant No. PGC2018-099645-B-I00), the European Research
Council (Grant No. Adv-883739), Fundació la Marató de TV3 (201903-30-31-32), the
European Commission (Grant No. H2020-FETPROACT-01-2016-731957), La Caixa Foundation
and the Biomedical Research Center Consortium in Red (Grant No. CB15/00153) at the
Carlos III Health Institute, Ministry of Science and Innovation. IBEC is recipient
of a Severo Ochoa Award of Excellence from the Spanish Ministry of Economy, Trade
and Business.
article_processing_charge: No
article_type: original
author:
- first_name: Eléonore
full_name: Vercruysse, Eléonore
last_name: Vercruysse
- first_name: David
full_name: Brückner, David
id: e1e86031-6537-11eb-953a-f7ab92be508d
last_name: Brückner
orcid: 0000-0001-7205-2975
- first_name: Manuel
full_name: Gómez-González, Manuel
last_name: Gómez-González
- first_name: Alexandre
full_name: Remson, Alexandre
last_name: Remson
- first_name: Marine
full_name: Luciano, Marine
last_name: Luciano
- first_name: Yohalie
full_name: Kalukula, Yohalie
last_name: Kalukula
- first_name: Leone
full_name: Rossetti, Leone
last_name: Rossetti
- first_name: Xavier
full_name: Trepat, Xavier
last_name: Trepat
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Sylvain
full_name: Gabriele, Sylvain
last_name: Gabriele
citation:
ama: Vercruysse E, Brückner D, Gómez-González M, et al. Geometry-driven migration
efficiency of autonomous epithelial cell clusters. Nature Physics. 2024;20:1492-1500.
doi:10.1038/s41567-024-02532-x
apa: Vercruysse, E., Brückner, D., Gómez-González, M., Remson, A., Luciano, M.,
Kalukula, Y., … Gabriele, S. (2024). Geometry-driven migration efficiency of autonomous
epithelial cell clusters. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-024-02532-x
chicago: Vercruysse, Eléonore, David Brückner, Manuel Gómez-González, Alexandre
Remson, Marine Luciano, Yohalie Kalukula, Leone Rossetti, Xavier Trepat, Edouard
B Hannezo, and Sylvain Gabriele. “Geometry-Driven Migration Efficiency of Autonomous
Epithelial Cell Clusters.” Nature Physics. Springer Nature, 2024. https://doi.org/10.1038/s41567-024-02532-x.
ieee: E. Vercruysse et al., “Geometry-driven migration efficiency of autonomous
epithelial cell clusters,” Nature Physics, vol. 20. Springer Nature, pp.
1492–1500, 2024.
ista: Vercruysse E, Brückner D, Gómez-González M, Remson A, Luciano M, Kalukula
Y, Rossetti L, Trepat X, Hannezo EB, Gabriele S. 2024. Geometry-driven migration
efficiency of autonomous epithelial cell clusters. Nature Physics. 20, 1492–1500.
mla: Vercruysse, Eléonore, et al. “Geometry-Driven Migration Efficiency of Autonomous
Epithelial Cell Clusters.” Nature Physics, vol. 20, Springer Nature, 2024,
pp. 1492–500, doi:10.1038/s41567-024-02532-x.
short: E. Vercruysse, D. Brückner, M. Gómez-González, A. Remson, M. Luciano, Y.
Kalukula, L. Rossetti, X. Trepat, E.B. Hannezo, S. Gabriele, Nature Physics 20
(2024) 1492–1500.
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: All data are available from the corresponding authors upon
request. Source data are provided with this paper.
date_created: 2024-07-16T12:32:17Z
date_published: 2024-09-01T00:00:00Z
date_updated: 2026-10-01T11:02:43Z
day: '01'
department:
- _id: EdHa
doi: 10.1038/s41567-024-02532-x
ec_funded: 1
external_id:
isi:
- '001250246200004'
fulldoi: https://doi.org/10.1038/s41567-024-02532-x
intvolume: ' 20'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2022.07.17.500364
month: '09'
oa: 1
oa_version: Preprint
page: 1492-1500
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
- _id: 34e2a5b5-11ca-11ed-8bc3-b2265616ef0b
grant_number: ALTF 343-2022
name: A mechano-chemical theory for stem cell fate decisions in organoid development
publication: Nature Physics
publication_identifier:
eissn:
- 1745-2481
issn:
- 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/a-railroad-of-cells/
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Geometry-driven migration efficiency of autonomous epithelial cell clusters
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 20
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '18446'
abstract:
- lang: eng
text: How living systems achieve precision in form and function despite their intrinsic
stochasticity is a fundamental yet ongoing question in biology. We generated morphomaps
of preimplantation embryogenesis in mouse, rabbit, and monkey embryos, and these
morphomaps revealed that although blastomere divisions desynchronized passively,
8-cell embryos converged toward robust three-dimensional shapes. Using topological
analysis and genetic perturbations, we found that embryos progressively changed
their cellular connectivity to a preferred topology, which could be predicted
by a physical model in which actomyosin contractility and noise facilitate topological
transitions, lowering surface energy. This mechanism favored regular embryo packing
and promoted a higher number of inner cells in the 16-cell embryo. Synchronized
division reduced embryo packing and generated substantially more misallocated
cells and fewer inner-cell–mass cells. These findings suggest that stochasticity
in division timing contributes to robust patterning.
acknowledgement: "We are grateful to the members of the Hiiragi laboratory for discussions
and comments on the manuscript: R. Bloehs, S. Friese, S. Hozeifi, L. Pérez, and
W. Schwarzer for their technical support; V. Janssen for establishing the PAB protocol;
members of the Tsukiyama group for the animal care with monkeys, in particular H.
Tsuchiya and M. Nakaya; Unité Commune d’Expérimentation Animale (UCEA, Jouy-en-Josas,
France) for the animal care with rabbits; the EMBL electronic and mechanical workshops
and the EMBL animal facility for their support; We thank Luxendo for the close collaboration
in developing the light-sheet microscopy for mammalian embryos.\r\nFunding: This
work was funded by the following: EMBL Interdisciplinary Postdoc Program (EIPOD)
under Marie Sklodowska Curie Actions COFUND III RTD (to D.F.); JSPS Overseas Research
Fellowship (to T.I.); Field of excellence “Complexity of life in basic research
and innovation” of the University of Graz (to B.C.M.); European Research Council,
ERC Advanced Grant “SelforganisingEmbryo”, grant agreement 742732; ERC Advanced
Grant “COORDINATION” grant agreement 101055287 (to T.H.); Stichting LSH-TKI, grant
LSHM21020 (to T.H.) JSPS KAKENHI grants JP21H05038 and JP22H05166 (to T.H.)"
article_number: eadh1145
article_processing_charge: No
article_type: original
author:
- first_name: Dimitri
full_name: Fabrèges, Dimitri
last_name: Fabrèges
- first_name: Bernat
full_name: Corominas-Murtra, Bernat
id: 43BE2298-F248-11E8-B48F-1D18A9856A87
last_name: Corominas-Murtra
orcid: 0000-0001-9806-5643
- first_name: Prachiti
full_name: Moghe, Prachiti
last_name: Moghe
- first_name: Alison
full_name: Kickuth, Alison
last_name: Kickuth
- first_name: Takafumi
full_name: Ichikawa, Takafumi
last_name: Ichikawa
- first_name: Chizuru
full_name: Iwatani, Chizuru
last_name: Iwatani
- first_name: Tomoyuki
full_name: Tsukiyama, Tomoyuki
last_name: Tsukiyama
- first_name: Nathalie
full_name: Daniel, Nathalie
last_name: Daniel
- first_name: Julie
full_name: Gering, Julie
last_name: Gering
- first_name: Anniek
full_name: Stokkermans, Anniek
last_name: Stokkermans
- first_name: Adrian
full_name: Wolny, Adrian
last_name: Wolny
- first_name: Anna
full_name: Kreshuk, Anna
last_name: Kreshuk
- first_name: Véronique
full_name: Duranthon, Véronique
last_name: Duranthon
- first_name: Virginie
full_name: Uhlman, Virginie
last_name: Uhlman
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Takashi
full_name: Hiiragi, Takashi
last_name: Hiiragi
citation:
ama: Fabrèges D, Corominas-Murtra B, Moghe P, et al. Temporal variability and cell
mechanics control robustness in mammalian embryogenesis. Science. 2024;386(6718).
doi:10.1126/science.adh1145
apa: Fabrèges, D., Corominas-Murtra, B., Moghe, P., Kickuth, A., Ichikawa, T., Iwatani,
C., … Hiiragi, T. (2024). Temporal variability and cell mechanics control robustness
in mammalian embryogenesis. Science. AAAS. https://doi.org/10.1126/science.adh1145
chicago: Fabrèges, Dimitri, Bernat Corominas-Murtra, Prachiti Moghe, Alison Kickuth,
Takafumi Ichikawa, Chizuru Iwatani, Tomoyuki Tsukiyama, et al. “Temporal Variability
and Cell Mechanics Control Robustness in Mammalian Embryogenesis.” Science.
AAAS, 2024. https://doi.org/10.1126/science.adh1145.
ieee: D. Fabrèges et al., “Temporal variability and cell mechanics control
robustness in mammalian embryogenesis,” Science, vol. 386, no. 6718. AAAS,
2024.
ista: Fabrèges D, Corominas-Murtra B, Moghe P, Kickuth A, Ichikawa T, Iwatani C,
Tsukiyama T, Daniel N, Gering J, Stokkermans A, Wolny A, Kreshuk A, Duranthon
V, Uhlman V, Hannezo EB, Hiiragi T. 2024. Temporal variability and cell mechanics
control robustness in mammalian embryogenesis. Science. 386(6718), eadh1145.
mla: Fabrèges, Dimitri, et al. “Temporal Variability and Cell Mechanics Control
Robustness in Mammalian Embryogenesis.” Science, vol. 386, no. 6718, eadh1145,
AAAS, 2024, doi:10.1126/science.adh1145.
short: D. Fabrèges, B. Corominas-Murtra, P. Moghe, A. Kickuth, T. Ichikawa, C. Iwatani,
T. Tsukiyama, N. Daniel, J. Gering, A. Stokkermans, A. Wolny, A. Kreshuk, V. Duranthon,
V. Uhlman, E.B. Hannezo, T. Hiiragi, Science 386 (2024).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: "All original code and data reported in this paper is publicly
available as of the date of publication on Zenodo (124).\r\n124\r\nD. Fabrèges,
B. Corominas-Murtra, P. Moghe, A. Kickuth, T. Ichikawa, C. Iwatani, T. Tsukiyama,
N. Daniel, J. Gering, A. Stokkermans, A. Wolny, A. Kreshuk, V. Duranthon, V. Uhlmann,
E. Hannezo, T. Hiiragi, Temporal variability and cell mechanics control robustness
in mammalian embryogenesis, version 1.0, Zenodo (2024); https://doi.org/10.5281/ZENODO.12819781."
date_created: 2024-10-20T22:02:06Z
date_published: 2024-10-11T00:00:00Z
date_updated: 2026-10-01T10:54:32Z
day: '11'
department:
- _id: EdHa
doi: 10.1126/science.adh1145
external_id:
isi:
- '001422132300018'
pmid:
- '39388574'
fulldoi: https://doi.org/10.1126/science.adh1145
intvolume: ' 386'
isi: 1
issue: '6718'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://hal.inrae.fr/hal-04447081v1/file/2023.01.24.525420.full.pdf
month: '10'
oa: 1
oa_version: Submitted Version
pmid: 1
publication: Science
publication_identifier:
eissn:
- 1095-9203
publication_status: published
publisher: AAAS
quality_controlled: '1'
related_material:
record:
- id: '23023'
relation: research_data
status: public
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Temporal variability and cell mechanics control robustness in mammalian embryogenesis
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 386
year: '2024'
...
---
_id: '18071'
abstract:
- lang: eng
text: Recent advancements on DAG-based consensus protocols allow for blockchains
with improved metrics and properties, such as throughput and censorship-resistance.
Variants of the Bullshark [18] consensus protocol are adopted for practical use
by the Sui blockchain, for improved latency. However, the protocol is leader-based,
and is strongly affected by crashed leaders that can lead to various performance
issues, for example, decreased transaction throughput. In this paper, we propose
HammerHead, a DAG-based consensus protocol, that is inspired by Carousel [8] and
provides Leader-Utilization. Our proposal differs from Carousel, which is built
for a chained consensus protocol; in HammerHead chain quality is inherited by
the DAG. HammerHead needs to preserve safety and liveness, despite validators
committing leader vertices asynchronously. The key idea is to update leader schedules
dynamically, based on the validators' scores during the previous schedule. We
implement HammerHead and show a minor improvement in performance for cases without
faults. The major improvements in comparison to Bullshark appear in faulty settings.
Specifically, we show a drastic, 2x-latency improvement and up to 40% increased
throughput when crash faults occur (100 validators, 33 faults).
acknowledgement: This work is supported by Mysten Labs. We thank the Mysten Labs Engineering
teams for valuable feedback broadly, and specifically to Laura Makdah for helping
implementing the early reputation score system for validators and Dmitry Perelman
for managing the overall implementation effort.
article_processing_charge: No
arxiv: 1
author:
- first_name: Giorgos
full_name: Tsimos, Giorgos
last_name: Tsimos
- first_name: Anastasios
full_name: Kichidis, Anastasios
last_name: Kichidis
- first_name: Alberto
full_name: Sonnino, Alberto
last_name: Sonnino
- first_name: Eleftherios
full_name: Kokoris Kogias, Eleftherios
id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
last_name: Kokoris Kogias
orcid: 0000-0002-8827-3382
citation:
ama: 'Tsimos G, Kichidis A, Sonnino A, Kokoris Kogias E. HammerHead: Leader reputation
for dynamic scheduling. In: Proceedings - International Conference on Distributed
Computing Systems. IEEE; 2024:1377-1387. doi:10.1109/ICDCS60910.2024.00129'
apa: 'Tsimos, G., Kichidis, A., Sonnino, A., & Kokoris Kogias, E. (2024). HammerHead:
Leader reputation for dynamic scheduling. In Proceedings - International Conference
on Distributed Computing Systems (pp. 1377–1387). Jersey City, NJ, United
States: IEEE. https://doi.org/10.1109/ICDCS60910.2024.00129'
chicago: 'Tsimos, Giorgos, Anastasios Kichidis, Alberto Sonnino, and Eleftherios
Kokoris Kogias. “HammerHead: Leader Reputation for Dynamic Scheduling.” In Proceedings
- International Conference on Distributed Computing Systems, 1377–87. IEEE,
2024. https://doi.org/10.1109/ICDCS60910.2024.00129.'
ieee: 'G. Tsimos, A. Kichidis, A. Sonnino, and E. Kokoris Kogias, “HammerHead: Leader
reputation for dynamic scheduling,” in Proceedings - International Conference
on Distributed Computing Systems, Jersey City, NJ, United States, 2024, pp.
1377–1387.'
ista: 'Tsimos G, Kichidis A, Sonnino A, Kokoris Kogias E. 2024. HammerHead: Leader
reputation for dynamic scheduling. Proceedings - International Conference on Distributed
Computing Systems. ICDCS: International Conference on Distributed Computing Systems,
1377–1387.'
mla: 'Tsimos, Giorgos, et al. “HammerHead: Leader Reputation for Dynamic Scheduling.”
Proceedings - International Conference on Distributed Computing Systems,
IEEE, 2024, pp. 1377–87, doi:10.1109/ICDCS60910.2024.00129.'
short: G. Tsimos, A. Kichidis, A. Sonnino, E. Kokoris Kogias, in:, Proceedings -
International Conference on Distributed Computing Systems, IEEE, 2024, pp. 1377–1387.
conference:
end_date: 2024-07-26
location: Jersey City, NJ, United States
name: 'ICDCS: International Conference on Distributed Computing Systems'
start_date: 2024-07-23
das_tickbox: '0'
date_created: 2024-09-15T22:01:41Z
date_published: 2024-07-26T00:00:00Z
date_updated: 2026-10-01T11:04:17Z
day: '26'
department:
- _id: ElKo
doi: 10.1109/ICDCS60910.2024.00129
external_id:
arxiv:
- '2309.12713'
isi:
- '001304430200120'
fulldoi: https://doi.org/10.1109/ICDCS60910.2024.00129
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/2309.12713
month: '07'
oa: 1
oa_version: Preprint
page: 1377-1387
publication: Proceedings - International Conference on Distributed Computing Systems
publication_identifier:
eissn:
- 2575-8411
isbn:
- '9798350386059'
issn:
- 1063-6927
publication_status: published
publisher: IEEE
quality_controlled: '1'
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: 'HammerHead: Leader reputation for dynamic scheduling'
type: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
_id: '17284'
abstract:
- lang: eng
text: Platelet homeostasis is essential for vascular integrity and immune defence1,2.
Although the process of platelet formation by fragmenting megakaryocytes (MKs;
thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms
required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis)
remains unclear3,4. Here we use intravital imaging to track the cellular dynamics
of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs)
as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver
IFNα to the MK niche triggering local on-demand proliferation and maturation of
MK progenitors. This pDC-dependent feedback loop is crucial for MK and platelet
homeostasis at steady state and under stress. pDCs are best known for their ability
to function as vigilant detectors of viral infection5. We show that virus-induced
activation of pDCs interferes with their function as homeostatic sensors of megakaryopoiesis.
Consequently, activation of pDCs by SARS-CoV-2 leads to excessive megakaryopoiesis.
Together, we identify a pDC-dependent homeostatic circuit that involves innate
immune sensing and demand-adapted release of inflammatory mediators to maintain
homeostasis of the megakaryocytic lineage.
acknowledgement: 'We thank S. Helmer, N. Blount, E. Raatz and Z. Sisic for technical
assistance. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German
Research Foundation) SFB 1123 (S.M. project B06); SFB 914 (S.M. projects B02 and
Z01, H.I.-A. project Z01, S.S. project A06, K.S. project B02, C. Schulz project
A10, B.W. project A02, C. Scheiermann project B09); SFB 1054 (T.B. project B03);
FOR2033 (F.G., R.A.J.O., S.M.); Individual research grant project ID: 514478744
(F.G.); Heisenberg Programme project ID: 514477451 (F.G.); the DZHK (German Center
for Cardiovascular Research) (MHA 1.4VD (S.M.), Postdoc Start-up Grant, 81×3600213
(F.G.)); and LMUexcellence NFF (F.G.). W.F. received funding from China Scholarship
Council (CSC, no. 201306270012). P.B. is supported by the German Research Foundation
(DFG, project IDs 322900939, 432698239 and 445703531), European Research Council
(ERC Consolidator grant no. 101001791) and the Federal Ministry of Education and
Research (BMBF, STOP-FSGS-01GM2202C and NATON within the framework of the Network
of University Medicine, no. 01KX2121). S.v.S. is supported by the START-Program
of the Faculty of Medicine of the RWTH Aachen University (AZ 125/17). A.D. and S.E.
are supported by the German Research Foundation (SFB TRR 267); S.E. by the BMBF
in the framework of the Cluster4future program (CNATM—Cluster for Nucleic Acid Therapeutics
Munich). This project has received funding from the European Research Council (ERC)
under the European Union’s Horizon 2020 research and innovation programme (grant
agreement no. 833440 to S.M.). F.G. received funding from the European Union’s Horizon
2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement
no. 747687. The project is funded by the European Union (ERC, MEKanics, 101078110).
Views and opinions expressed are those of the author(s) only and do not necessarily
reflect those of the European Union or the European Research Council Executive Agency.
Neither the European Union nor the granting authority can be held responsible for
them.'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Florian R
full_name: Gärtner, Florian R
id: 397A88EE-F248-11E8-B48F-1D18A9856A87
last_name: Gärtner
orcid: 0000-0001-6120-3723
- first_name: Hellen
full_name: Ishikawa-Ankerhold, Hellen
last_name: Ishikawa-Ankerhold
- first_name: Susanne
full_name: Stutte, Susanne
last_name: Stutte
- first_name: Wenwen
full_name: Fu, Wenwen
last_name: Fu
- first_name: Jutta
full_name: Weitz, Jutta
last_name: Weitz
- first_name: Anne
full_name: Dueck, Anne
last_name: Dueck
- first_name: Bhavishya
full_name: Nelakuditi, Bhavishya
last_name: Nelakuditi
- first_name: Valeria
full_name: Fumagalli, Valeria
last_name: Fumagalli
- first_name: Dominic
full_name: Van Den Heuvel, Dominic
last_name: Van Den Heuvel
- first_name: Larissa
full_name: Belz, Larissa
last_name: Belz
- first_name: Gulnoza
full_name: Sobirova, Gulnoza
last_name: Sobirova
- first_name: Zhe
full_name: Zhang, Zhe
last_name: Zhang
- first_name: Anna
full_name: Titova, Anna
last_name: Titova
- first_name: Alejandro Martinez
full_name: Navarro, Alejandro Martinez
last_name: Navarro
- first_name: Kami
full_name: Pekayvaz, Kami
last_name: Pekayvaz
- first_name: Michael
full_name: Lorenz, Michael
last_name: Lorenz
- first_name: Louisa
full_name: Von Baumgarten, Louisa
last_name: Von Baumgarten
- first_name: Jan
full_name: Kranich, Jan
last_name: Kranich
- first_name: Tobias
full_name: Straub, Tobias
last_name: Straub
- first_name: Bastian
full_name: Popper, Bastian
last_name: Popper
- first_name: Vanessa
full_name: Zheden, Vanessa
id: 39C5A68A-F248-11E8-B48F-1D18A9856A87
last_name: Zheden
orcid: 0000-0002-9438-4783
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Chenglong
full_name: Guo, Chenglong
last_name: Guo
- first_name: Guido
full_name: Piontek, Guido
last_name: Piontek
- first_name: Saskia
full_name: Von Stillfried, Saskia
last_name: Von Stillfried
- first_name: Peter
full_name: Boor, Peter
last_name: Boor
- first_name: Marco
full_name: Colonna, Marco
last_name: Colonna
- first_name: Sebastian
full_name: Clauß, Sebastian
last_name: Clauß
- first_name: Christian
full_name: Schulz, Christian
last_name: Schulz
- first_name: Thomas
full_name: Brocker, Thomas
last_name: Brocker
- first_name: Barbara
full_name: Walzog, Barbara
last_name: Walzog
- first_name: Christoph
full_name: Scheiermann, Christoph
last_name: Scheiermann
- first_name: William C.
full_name: Aird, William C.
last_name: Aird
- first_name: Claus
full_name: Nerlov, Claus
last_name: Nerlov
- first_name: Konstantin
full_name: Stark, Konstantin
last_name: Stark
- first_name: Tobias
full_name: Petzold, Tobias
last_name: Petzold
- first_name: Stefan
full_name: Engelhardt, Stefan
last_name: Engelhardt
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Martina
full_name: Rudelius, Martina
last_name: Rudelius
- first_name: Robert A.J.
full_name: Oostendorp, Robert A.J.
last_name: Oostendorp
- first_name: Matteo
full_name: Iannacone, Matteo
last_name: Iannacone
- first_name: Matthias
full_name: Heinig, Matthias
last_name: Heinig
- first_name: Steffen
full_name: Massberg, Steffen
last_name: Massberg
citation:
ama: Gärtner FR, Ishikawa-Ankerhold H, Stutte S, et al. Plasmacytoid dendritic cells
control homeostasis of megakaryopoiesis. Nature. 2024;631:645-653. doi:10.1038/s41586-024-07671-y
apa: Gärtner, F. R., Ishikawa-Ankerhold, H., Stutte, S., Fu, W., Weitz, J., Dueck,
A., … Massberg, S. (2024). Plasmacytoid dendritic cells control homeostasis of
megakaryopoiesis. Nature. Springer Nature. https://doi.org/10.1038/s41586-024-07671-y
chicago: Gärtner, Florian R, Hellen Ishikawa-Ankerhold, Susanne Stutte, Wenwen Fu,
Jutta Weitz, Anne Dueck, Bhavishya Nelakuditi, et al. “Plasmacytoid Dendritic
Cells Control Homeostasis of Megakaryopoiesis.” Nature. Springer Nature,
2024. https://doi.org/10.1038/s41586-024-07671-y.
ieee: F. R. Gärtner et al., “Plasmacytoid dendritic cells control homeostasis
of megakaryopoiesis,” Nature, vol. 631. Springer Nature, pp. 645–653, 2024.
ista: Gärtner FR, Ishikawa-Ankerhold H, Stutte S, Fu W, Weitz J, Dueck A, Nelakuditi
B, Fumagalli V, Van Den Heuvel D, Belz L, Sobirova G, Zhang Z, Titova A, Navarro
AM, Pekayvaz K, Lorenz M, Von Baumgarten L, Kranich J, Straub T, Popper B, Zheden
V, Kaufmann W, Guo C, Piontek G, Von Stillfried S, Boor P, Colonna M, Clauß S,
Schulz C, Brocker T, Walzog B, Scheiermann C, Aird WC, Nerlov C, Stark K, Petzold
T, Engelhardt S, Sixt MK, Hauschild R, Rudelius M, Oostendorp RAJ, Iannacone M,
Heinig M, Massberg S. 2024. Plasmacytoid dendritic cells control homeostasis of
megakaryopoiesis. Nature. 631, 645–653.
mla: Gärtner, Florian R., et al. “Plasmacytoid Dendritic Cells Control Homeostasis
of Megakaryopoiesis.” Nature, vol. 631, Springer Nature, 2024, pp. 645–53,
doi:10.1038/s41586-024-07671-y.
short: F.R. Gärtner, H. Ishikawa-Ankerhold, S. Stutte, W. Fu, J. Weitz, A. Dueck,
B. Nelakuditi, V. Fumagalli, D. Van Den Heuvel, L. Belz, G. Sobirova, Z. Zhang,
A. Titova, A.M. Navarro, K. Pekayvaz, M. Lorenz, L. Von Baumgarten, J. Kranich,
T. Straub, B. Popper, V. Zheden, W. Kaufmann, C. Guo, G. Piontek, S. Von Stillfried,
P. Boor, M. Colonna, S. Clauß, C. Schulz, T. Brocker, B. Walzog, C. Scheiermann,
W.C. Aird, C. Nerlov, K. Stark, T. Petzold, S. Engelhardt, M.K. Sixt, R. Hauschild,
M. Rudelius, R.A.J. Oostendorp, M. Iannacone, M. Heinig, S. Massberg, Nature 631
(2024) 645–653.
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: Imaging and flow cytometry raw data are available on request.
scRNA-seq data are accessible at the GEO (GSE261996). Bulk RNA-seq data are accessible
at the GEO (GSE185488). Source data are provided with this paper.
date_created: 2024-07-21T22:01:02Z
date_published: 2024-07-18T00:00:00Z
date_updated: 2026-10-01T11:17:11Z
day: '18'
ddc:
- '570'
department:
- _id: EM-Fac
- _id: MiSi
- _id: Bio
doi: 10.1038/s41586-024-07671-y
ec_funded: 1
external_id:
isi:
- '001281636500020'
pmid:
- '38987596'
file:
- access_level: open_access
checksum: aa004afc72d2489f0fb0fcbc9919fbbd
content_type: application/pdf
creator: dernst
date_created: 2024-07-22T06:16:11Z
date_updated: 2024-07-22T06:16:11Z
file_id: '17286'
file_name: 2024_Nature_Gaertner.pdf
file_size: 15704819
relation: main_file
success: 1
file_date_updated: 2024-07-22T06:16:11Z
fulldoi: https://doi.org/10.1038/s41586-024-07671-y
has_accepted_license: '1'
intvolume: ' 631'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 645-653
pmid: 1
project:
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '747687'
name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/heiniglab/gaertner_megakaryocytes
researchdata_availability: upon request
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 631
year: '2024'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '18920'
abstract:
- lang: eng
text: The globally distributed marine alga Emiliania huxleyi has cooling effect
on the Earth’s climate. The population density of E. huxleyi is restricted by
Nucleocytoviricota viruses, including E. huxleyi virus 201 (EhV-201). Despite
the impact of E. huxleyi viruses on the climate, there is limited information
about their structure and replication. Here, we show that the dsDNA genome inside
the EhV-201 virion is protected by an inner membrane, capsid, and outer membrane.
EhV-201 virions infect E. huxleyi by using fivefold vertices to bind to and fuse
the virus’ inner membrane with the cell plasma membrane. Progeny virions assemble
in the cytoplasm at the surface of endoplasmic reticulum–derived membrane segments.
Genome packaging initiates synchronously with the capsid assembly and completes
through an aperture in the forming capsid. The genome-filled capsids acquire an
outer membrane by budding into intracellular vesicles. EhV-201 infection induces
a loss of surface protective layers from E. huxleyi cells, which enables the continuous
release of virions by exocytosis.
acknowledgement: We acknowledge (i) the Cryo-Electron Microscopy and Tomography Core
Facility and Proteomics Core Facility of the Central European Institute of Technology
(CEITEC), Masaryk University, supported by the Ministry of Education, Youth, and
Sports of the Czech Republic (grant LM2018127); (ii) the Cellular Imaging Core Facility
supported by the Czech-BioImaging large RI project (LM2018129 funded by MEYS CR);
and (iii) Plant Sciences Core Facility for support with obtaining scientific data
presented here. We acknowledge support from the project National Institute of Virology
and Bacteriology (Program EXCELES, ID project no. LX22NPO5103), funded by the European
Union - Next Generation EU. This work received funding from the Czech Science Foundation
grant GX 19-259882X to P.P., from European Regional Development Fund-Project “MSCAfellow2@MUNI”
(no. CZ.02.2.69/0.0/0.0/18_070/0009846) to C.R.B., and from Brno PhD talent scholarship
funded by Brno city municipality to M.H.
article_number: 'eadk1954 '
article_processing_charge: Yes
article_type: original
author:
- first_name: Miroslav
full_name: Homola, Miroslav
last_name: Homola
- first_name: Renate Carina
full_name: Büttner, Renate Carina
id: 3b7984c9-17ff-11ed-b6fe-f943c4a5b626
last_name: Büttner
- first_name: Tibor
full_name: Füzik, Tibor
last_name: Füzik
- first_name: Pavel
full_name: Křepelka, Pavel
last_name: Křepelka
- first_name: Radka
full_name: Holbová, Radka
last_name: Holbová
- first_name: Jiří
full_name: Nováček, Jiří
last_name: Nováček
- first_name: Marten L.
full_name: Chaillet, Marten L.
last_name: Chaillet
- first_name: Jakub
full_name: Žák, Jakub
last_name: Žák
- first_name: Danyil
full_name: Grybchuk, Danyil
last_name: Grybchuk
- first_name: Friedrich
full_name: Förster, Friedrich
last_name: Förster
- first_name: William H.
full_name: Wilson, William H.
last_name: Wilson
- first_name: Declan C.
full_name: Schroeder, Declan C.
last_name: Schroeder
- first_name: Pavel
full_name: Plevka, Pavel
last_name: Plevka
citation:
ama: Homola M, Büttner RC, Füzik T, et al. Structure and replication cycle of a
virus infecting climate-modulating alga Emiliania huxleyi. Science Advances.
2024;10(15). doi:10.1126/sciadv.adk1954
apa: Homola, M., Büttner, R. C., Füzik, T., Křepelka, P., Holbová, R., Nováček,
J., … Plevka, P. (2024). Structure and replication cycle of a virus infecting
climate-modulating alga Emiliania huxleyi. Science Advances. American Association
for the Advancement of Science. https://doi.org/10.1126/sciadv.adk1954
chicago: Homola, Miroslav, Renate Carina Büttner, Tibor Füzik, Pavel Křepelka, Radka
Holbová, Jiří Nováček, Marten L. Chaillet, et al. “Structure and Replication Cycle
of a Virus Infecting Climate-Modulating Alga Emiliania Huxleyi.” Science Advances.
American Association for the Advancement of Science, 2024. https://doi.org/10.1126/sciadv.adk1954.
ieee: M. Homola et al., “Structure and replication cycle of a virus infecting
climate-modulating alga Emiliania huxleyi,” Science Advances, vol. 10,
no. 15. American Association for the Advancement of Science, 2024.
ista: Homola M, Büttner RC, Füzik T, Křepelka P, Holbová R, Nováček J, Chaillet
ML, Žák J, Grybchuk D, Förster F, Wilson WH, Schroeder DC, Plevka P. 2024. Structure
and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi.
Science Advances. 10(15), eadk1954.
mla: Homola, Miroslav, et al. “Structure and Replication Cycle of a Virus Infecting
Climate-Modulating Alga Emiliania Huxleyi.” Science Advances, vol. 10,
no. 15, eadk1954, American Association for the Advancement of Science, 2024, doi:10.1126/sciadv.adk1954.
short: M. Homola, R.C. Büttner, T. Füzik, P. Křepelka, R. Holbová, J. Nováček, M.L.
Chaillet, J. Žák, D. Grybchuk, F. Förster, W.H. Wilson, D.C. Schroeder, P. Plevka,
Science Advances 10 (2024).
das_tickbox: '1'
dataavailabilitystatement: 'Cryo-EM maps and structure coordinates were deposited
to the Electron Microscopy Data Bank (EMDB) and Protein Data Bank (PDB), respectively,
with the following accession numbers: (i) EhV-201 virion vertex reconstructed using
a single-particle approach and a mask with the diameter of 50 nm (EMD-17650); (ii)
EhV-201 virion vertex reconstructed using sub-tomogram averaging and a mask with
the diameter of 50 nm (EMD-17649); (iii) EhV-201 virion vertex reconstructed using
sub-tomogram averaging and a mask with the diameter of 50 nm and a mask covering
only the capsid layer (EMD-19036) and the fitted structure of AlphaFold2 predicted
EhV-201 major capsid protein and penton protein (PDB 8RBT); (iv) EhV-201 virion
vertex reconstructed by sub-tomogram averaging and a mask with the diameter of 120
nm (EMD-17651); and (v) composite map of the EhV201 virion (EMD-19035) and corresponding
structure of icosahedral asymmetric unit (PDB 8RBS). All custom scripts used during
tomographic reconstruction have been made available at https://github.com/fuzikt/tomostarpy.
Additional files have been made available at https://doi.org/10.5061/dryad.p5hqbzkw0:
(i) cryo-ET tilt series of lamellas of control and EhV-201 infected E. huxleyi cells;
(ii) segmentations of cryo-tomograms of infected and control cells; (iii) block
face imaging data series of high-pressure frozen and resin-embedded E. huxleyi infected
by EhV-201; (iv) scripts used during tomographic reconstruction; (v) fluorescence
microscopy images of E. huxleyi infected by EhV-201; and (vi) mass spectrometry
report of EhV-201 virion protein composition. Cryo-ET tilt series used for EhV-201
virion structure determination were deposited to EMPIAR and linked to the file EMD-17649.
All other data needed to evaluate the conclusions in the paper are present in the
paper and/or the Supplementary Materials.'
date_created: 2025-01-27T14:32:34Z
date_published: 2024-04-01T00:00:00Z
date_updated: 2026-10-01T11:15:30Z
day: '01'
ddc:
- '570'
department:
- _id: EM-Fac
doi: 10.1126/sciadv.adk1954
external_id:
pmid:
- '38598627'
file:
- access_level: open_access
checksum: 291dd7ceccbe6bfd8e0a9157584f88e9
content_type: application/pdf
creator: dernst
date_created: 2025-01-27T14:40:08Z
date_updated: 2025-01-27T14:40:08Z
file_id: '18921'
file_name: 2024_ScienceAdv_Homola.pdf
file_size: 40623405
relation: main_file
success: 1
file_date_updated: 2025-01-27T14:40:08Z
fulldoi: https://doi.org/10.1126/sciadv.adk1954
has_accepted_license: '1'
intvolume: ' 10'
issue: '15'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: Science Advances
publication_identifier:
eissn:
- 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
link:
- relation: software
url: ' https://github.com/fuzikt/tomostarpy.'
record:
- id: '23025'
relation: research_data
status: public
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Structure and replication cycle of a virus infecting climate-modulating alga
Emiliania huxleyi
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 10
year: '2024'
...
---
_id: '18052'
abstract:
- lang: eng
text: Sodium dodecyl sulfate-digested freeze-fracture replica labeling (SDS-FRL)
is an electron microscope (EM) sample preparation technique which allows for high-resolution
visualization of membrane proteins with high sensitivity. However, image acquisition
of specific replica profiles such as synapses in a large field of EM view needs
a valid experience and a long time for manual searching. Here, we describe how
to utilize deep learning for automatizing image acquisition of specific profiles
of interest in replica samples. This protocol facilitates the labor-intensive
collection of EM images, in particular for rare profiles. We provide instructions
for using SerialEM image acquisition software in conjunction with object detection
by our newly developed deep learning software DarEM, to automatically acquire
tilt series of all synapses in a selected region. We then show how to perform
a mostly automated analysis of gold particle labeling in the acquired images by
utilizing Darea software.
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: This research was supported by the European Research Council Advanced
Grant 694539 to RS and by the Scientific Service Units of IST Austria through resources
provided by the Electron Microscopy Facility.
alternative_title:
- Neuromethods
article_processing_charge: No
author:
- first_name: David
full_name: Kleindienst, David
id: 42E121A4-F248-11E8-B48F-1D18A9856A87
last_name: Kleindienst
- first_name: Tommaso
full_name: Costanzo, Tommaso
id: D93824F4-D9BA-11E9-BB12-F207E6697425
last_name: Costanzo
orcid: 0000-0001-9732-3815
- 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, Costanzo T, Shigemoto R. Automated Imaging and Analysis of
Synapses in Freeze-Fracture Replica Samples with Deep Learning. In: Lübke JHR,
Rollenhagen A, eds. New Aspects in Analyzing the Synaptic Organization of the
Brain. 1st ed. New York: Springer Nature; 2024:123-137. doi:10.1007/978-1-0716-4019-7_8'
apa: 'Kleindienst, D., Costanzo, T., & Shigemoto, R. (2024). Automated Imaging
and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning.
In J. H. R. Lübke & A. Rollenhagen (Eds.), New Aspects in Analyzing the
Synaptic Organization of the Brain (1st ed., pp. 123–137). New York: Springer
Nature. https://doi.org/10.1007/978-1-0716-4019-7_8'
chicago: 'Kleindienst, David, Tommaso Costanzo, and Ryuichi Shigemoto. “Automated
Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep
Learning.” In New Aspects in Analyzing the Synaptic Organization of the Brain,
edited by Joachim H.R. Lübke and Astrid Rollenhagen, 1st ed., 123–37. New York:
Springer Nature, 2024. https://doi.org/10.1007/978-1-0716-4019-7_8.'
ieee: 'D. Kleindienst, T. Costanzo, and R. Shigemoto, “Automated Imaging and Analysis
of Synapses in Freeze-Fracture Replica Samples with Deep Learning,” in New
Aspects in Analyzing the Synaptic Organization of the Brain, 1st ed., J. H.
R. Lübke and A. Rollenhagen, Eds. New York: Springer Nature, 2024, pp. 123–137.'
ista: 'Kleindienst D, Costanzo T, Shigemoto R. 2024.Automated Imaging and Analysis
of Synapses in Freeze-Fracture Replica Samples with Deep Learning. In: New Aspects
in Analyzing the Synaptic Organization of the Brain. Neuromethods, , 123–137.'
mla: Kleindienst, David, et al. “Automated Imaging and Analysis of Synapses in Freeze-Fracture
Replica Samples with Deep Learning.” New Aspects in Analyzing the Synaptic
Organization of the Brain, edited by Joachim H.R. Lübke and Astrid Rollenhagen,
1st ed., Springer Nature, 2024, pp. 123–37, doi:10.1007/978-1-0716-4019-7_8.
short: D. Kleindienst, T. Costanzo, R. Shigemoto, in:, J.H.R. Lübke, A. Rollenhagen
(Eds.), New Aspects in Analyzing the Synaptic Organization of the Brain, 1st ed.,
Springer Nature, New York, 2024, pp. 123–137.
corr_author: '1'
das_tickbox: '0'
date_created: 2024-09-10T12:32:38Z
date_published: 2024-08-27T00:00:00Z
date_updated: 2026-10-01T11:17:28Z
day: '27'
department:
- _id: EM-Fac
- _id: RySh
doi: 10.1007/978-1-0716-4019-7_8
ec_funded: 1
edition: '1'
editor:
- first_name: 'Joachim H.R. '
full_name: 'Lübke, Joachim H.R. '
last_name: Lübke
- first_name: Astrid
full_name: Rollenhagen, Astrid
last_name: Rollenhagen
fulldoi: https://doi.org/10.1007/978-1-0716-4019-7_8
language:
- iso: eng
month: '08'
oa_version: None
page: 123-137
place: New York
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'
publication: New Aspects in Analyzing the Synaptic Organization of the Brain
publication_identifier:
eisbn:
- '9781071640197'
eissn:
- 1940-6045
isbn:
- '9781071640180'
issn:
- 0893-2336
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples
with Deep Learning
type: book_chapter
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
_id: '14842'
abstract:
- lang: eng
text: Eva Benkova received a PhD in Biophysics at the Institute of Biophysics of
the Czech Academy of Sciences in 1998. After working as a postdoc at the Max Planck
Institute in Cologne and the Center for Plant Molecular Biology (ZMBP) in Tübingen,
she became a group leader at the Plant Systems Biology Department of the Vlaams
Instituut voor Biotechnologie (VIB) in Gent. In 2012, she transitioned to an Assistant
Professor position at the Institute of Science and Technology Austria (ISTA) where
she was later promoted to Professor. Since 2021, she has served as the Dean of
the ISTA Graduate School. As a plant developmental biologist, she focuses on unraveling
the molecular mechanisms and principles that underlie hormonal interactions in
plants. In her current work, she explores the intricate connections between hormones
and regulatory pathways that mediate the perception of environmental stimuli,
including abiotic stress and nitrate availability.
article_processing_charge: No
author:
- first_name: Eva
full_name: Benková, Eva
id: 38F4F166-F248-11E8-B48F-1D18A9856A87
last_name: Benková
orcid: 0000-0002-8510-9739
citation:
ama: Benková E. Eva Benkova. Vol 34. Elsevier; 2024:R3-R5. doi:10.1016/j.cub.2023.11.039
apa: Benková, E. (2024). Eva Benkova. Current Biology (Vol. 34, pp.
R3–R5). Elsevier. https://doi.org/10.1016/j.cub.2023.11.039
chicago: Benková, Eva. Eva Benkova. Current Biology. Vol. 34. Elsevier,
2024. https://doi.org/10.1016/j.cub.2023.11.039.
ieee: E. Benková, Eva Benkova, vol. 34, no. 1. Elsevier, 2024, pp. R3–R5.
ista: Benková E. 2024. Eva Benkova, Elsevier,p.
mla: Benková, Eva. “Eva Benkova.” Current Biology, vol. 34, no. 1, Elsevier,
2024, pp. R3–5, doi:10.1016/j.cub.2023.11.039.
short: E. Benková, Eva Benkova, Elsevier, 2024.
corr_author: '1'
das_tickbox: '0'
date_created: 2024-01-21T23:00:56Z
date_published: 2024-01-08T00:00:00Z
date_updated: 2026-10-01T11:17:58Z
day: '08'
ddc:
- '580'
department:
- _id: EvBe
doi: 10.1016/j.cub.2023.11.039
external_id:
pmid:
- '38194926'
fulldoi: https://doi.org/10.1016/j.cub.2023.11.039
intvolume: ' 34'
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.cub.2023.11.039
month: '01'
oa: 1
oa_version: Published Version
page: R3-R5
pmid: 1
publication: Current Biology
publication_identifier:
eissn:
- 1879-0445
publication_status: published
publisher: Elsevier
quality_controlled: '1'
researchdata_availability: not applicable
status: public
supplementarymaterial: no
title: Eva Benkova
type: other_academic_publication
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 34
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '23025'
abstract:
- lang: eng
text: The globally distributed marine alga Emiliania huxleyi produces reflective
calcite disks (coccoliths) that increase the albedo of ocean water and thus reduce
the heat absorption in the ocean, which cools the Earth’s climate. The population
density of E. huxleyi is restricted by Nucleocytoviricota viruses, including E.
huxleyi virus 201 (EhV-201). Despite the impact of E. huxleyi viruses on the climate,
there is limited information about their structure and replication. Here we show
that the dsDNA genome inside the EhV-201 virion is protected by an inner membrane,
capsid, and outer membrane decorated with numerous transmembrane proteins. The
virions are prone to deformation, and parts of their capsids deviate from the
icosahedral arrangement. EhV-201 virions infect E. huxleyi by using their fivefold
vertex to bind to a host cell and fuse the virus’s inner membrane with the plasma
membrane. Whereas the replication of EhV-201 probably occurs in the nucleus, virions
assemble in the cytoplasm at the surface of endoplasmic reticulum-derived membrane
segments. Genome packaging initiates synchronously with the capsid assembly and
completes through an aperture in the forming capsid. Upon the completion of genome
packaging, the capsids change conformation, which enables them to acquire an outer
membrane by budding into intracellular vesicles. EhV-201 infection induces a loss
of surface protective layers from E. huxleyi cells, which allows the continuous
release of virions by exocytosis. Our results provide insight into how EhVs bypass
the surface protective layers of E. huxleyi and exploit the organelles of an infected
cell for progeny assembly.
article_processing_charge: No
author:
- first_name: Miroslav
full_name: Homola, Miroslav
last_name: Homola
- first_name: Carina
full_name: Büttner, Carina
last_name: Büttner
- first_name: Tibor
full_name: Füzik, Tibor
last_name: Füzik
- first_name: Pavel
full_name: Krepelka, Pavel
last_name: Krepelka
- first_name: Radka
full_name: Holbová, Radka
last_name: Holbová
- first_name: Marten
full_name: Chaillet, Marten
last_name: Chaillet
- first_name: Jiří
full_name: Nováček, Jiří
last_name: Nováček
- first_name: Friedrich
full_name: Förster, Friedrich
last_name: Förster
- first_name: William
full_name: Wilson, William
last_name: Wilson
- first_name: Declan
full_name: Schroeder, Declan
last_name: Schroeder
- first_name: Pavel
full_name: Plevka, Pavel
last_name: Plevka
citation:
ama: 'Homola M, Büttner C, Füzik T, et al. Data: Structure and replication cycle
of a virus infecting climate-modulating alga Emiliania huxleyi. 2024. doi:10.5061/dryad.p5hqbzkw0'
apa: 'Homola, M., Büttner, C., Füzik, T., Krepelka, P., Holbová, R., Chaillet, M.,
… Plevka, P. (2024). Data: Structure and replication cycle of a virus infecting
climate-modulating alga Emiliania huxleyi. Dryad. https://doi.org/10.5061/dryad.p5hqbzkw0'
chicago: 'Homola, Miroslav, Carina Büttner, Tibor Füzik, Pavel Krepelka, Radka Holbová,
Marten Chaillet, Jiří Nováček, et al. “Data: Structure and Replication Cycle of
a Virus Infecting Climate-Modulating Alga Emiliania Huxleyi.” Dryad, 2024. https://doi.org/10.5061/dryad.p5hqbzkw0.'
ieee: 'M. Homola et al., “Data: Structure and replication cycle of a virus
infecting climate-modulating alga Emiliania huxleyi.” Dryad, 2024.'
ista: 'Homola M, Büttner C, Füzik T, Krepelka P, Holbová R, Chaillet M, Nováček
J, Förster F, Wilson W, Schroeder D, Plevka P. 2024. Data: Structure and replication
cycle of a virus infecting climate-modulating alga Emiliania huxleyi, Dryad, 10.5061/dryad.p5hqbzkw0.'
mla: 'Homola, Miroslav, et al. Data: Structure and Replication Cycle of a Virus
Infecting Climate-Modulating Alga Emiliania Huxleyi. Dryad, 2024, doi:10.5061/dryad.p5hqbzkw0.'
short: M. Homola, C. Büttner, T. Füzik, P. Krepelka, R. Holbová, M. Chaillet, J.
Nováček, F. Förster, W. Wilson, D. Schroeder, P. Plevka, (2024).
date_created: 2026-10-01T11:13:02Z
date_published: 2024-02-07T00:00:00Z
date_updated: 2026-10-01T11:15:29Z
day: '07'
ddc:
- '570'
department:
- _id: EM-Fac
doi: 10.5061/dryad.p5hqbzkw0
fulldoi: https://doi.org/10.5061/dryad.p5hqbzkw0
main_file_link:
- open_access: '1'
url: https://doi.org/10.5061/dryad.p5hqbzkw0
month: '02'
oa: 1
oa_version: None
publisher: Dryad
related_material:
record:
- id: '18920'
relation: used_in_publication
status: public
status: public
title: 'Data: Structure and replication cycle of a virus infecting climate-modulating
alga Emiliania huxleyi'
type: research_data_reference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
_id: '15146'
abstract:
- lang: eng
text: The extracellular matrix (ECM) serves as a scaffold for cells and plays an
essential role in regulating numerous cellular processes, including cell migration
and proliferation. Due to limitations in specimen preparation for conventional
room-temperature electron microscopy, we lack structural knowledge on how ECM
components are secreted, remodeled, and interact with surrounding cells. We have
developed a 3D-ECM platform compatible with sample thinning by cryo-focused ion
beam milling, the lift-out extraction procedure, and cryo-electron tomography.
Our workflow implements cell-derived matrices (CDMs) grown on EM grids, resulting
in a versatile tool closely mimicking ECM environments. This allows us to visualize
ECM for the first time in its hydrated, native context. Our data reveal an intricate
network of extracellular fibers, their positioning relative to matrix-secreting
cells, and previously unresolved structural entities. Our workflow and results
add to the structural atlas of the ECM, providing novel insights into its secretion
and assembly.
acknowledged_ssus:
- _id: LifeSc
- _id: ScienComp
- _id: EM-Fac
- _id: M-Shop
acknowledgement: "Open Access funding provided by IST Austria. We thank Armel Nicolas
and his team at the ISTA proteomics facility, Alois Schloegl, Stefano Elefante,
and colleagues at the ISTA Scientific Computing facility, Tommaso Constanzo and
Ludek Lovicar at the Electron Microsocpy Facility (EMF), and Thomas Menner at the
Miba Machine shop for their support. We also thank Wanda Kukulski (University of
Bern) as well as Darío Porley, Andreas Thader, and other members of the Schur group
for helpful discussions. Matt Swulius and Jessica Heebner provided great support
in using Dragonfly. We thank Dorotea Fracciolla (Art & Science) for support in figure
illustration.\r\n\r\nThis research was supported by the Scientific Service Units
of ISTA through resources provided by Scientific Computing, the Lab Support Facility,
and the Electron Microscopy Facility. We acknowledge funding support from the following
sources: Austrian Science Fund (FWF) grant P33367 (to F.K.M. Schur), the Federation
of European Biochemical Societies (to F.K.M. Schur), Niederösterreich (NÖ) Fonds
(to B. Zens), FWF grant E435 (to J.M. Hansen), European Research Council under the
European Union’s Horizon 2020 research (grant agreement No. 724373) (to M. Sixt),
and Jenny and Antti Wihuri Foundation (to J. Alanko). This publication has been
made possible in part by CZI grant DAF2021-234754 and grant DOI https://doi.org/10.37921/812628ebpcwg
from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community
Foundation (to F.K.M. Schur)."
article_number: e202309125
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Bettina
full_name: Zens, Bettina
id: 45FD126C-F248-11E8-B48F-1D18A9856A87
last_name: Zens
orcid: 0000-0002-9561-1239
- first_name: Florian
full_name: Fäßler, Florian
id: 404F5528-F248-11E8-B48F-1D18A9856A87
last_name: Fäßler
orcid: 0000-0001-7149-769X
- first_name: Jesse
full_name: Hansen, Jesse
id: 1063c618-6f9b-11ec-9123-f912fccded63
last_name: Hansen
orcid: 0000-0001-7967-2085
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Julia
full_name: Datler, Julia
id: 3B12E2E6-F248-11E8-B48F-1D18A9856A87
last_name: Datler
orcid: 0000-0002-3616-8580
- first_name: Victor-Valentin
full_name: Hodirnau, Victor-Valentin
id: 3661B498-F248-11E8-B48F-1D18A9856A87
last_name: Hodirnau
orcid: 0000-0003-3904-947X
- first_name: Vanessa
full_name: Zheden, Vanessa
id: 39C5A68A-F248-11E8-B48F-1D18A9856A87
last_name: Zheden
orcid: 0000-0002-9438-4783
- first_name: Jonna H
full_name: Alanko, Jonna H
id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87
last_name: Alanko
orcid: 0000-0002-7698-3061
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- 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: Zens B, Fäßler F, Hansen J, et al. Lift-out cryo-FIBSEM and cryo-ET reveal
the ultrastructural landscape of extracellular matrix. Journal of Cell Biology.
2024;223(6). doi:10.1083/jcb.202309125
apa: Zens, B., Fäßler, F., Hansen, J., Hauschild, R., Datler, J., Hodirnau, V.-V.,
… Schur, F. K. (2024). Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural
landscape of extracellular matrix. Journal of Cell Biology. Rockefeller
University Press. https://doi.org/10.1083/jcb.202309125
chicago: Zens, Bettina, Florian Fäßler, Jesse Hansen, Robert Hauschild, Julia Datler,
Victor-Valentin Hodirnau, Vanessa Zheden, Jonna H Alanko, Michael K Sixt, and
Florian KM Schur. “Lift-out Cryo-FIBSEM and Cryo-ET Reveal the Ultrastructural
Landscape of Extracellular Matrix.” Journal of Cell Biology. Rockefeller
University Press, 2024. https://doi.org/10.1083/jcb.202309125.
ieee: B. Zens et al., “Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural
landscape of extracellular matrix,” Journal of Cell Biology, vol. 223,
no. 6. Rockefeller University Press, 2024.
ista: Zens B, Fäßler F, Hansen J, Hauschild R, Datler J, Hodirnau V-V, Zheden V,
Alanko JH, Sixt MK, Schur FK. 2024. Lift-out cryo-FIBSEM and cryo-ET reveal the
ultrastructural landscape of extracellular matrix. Journal of Cell Biology. 223(6),
e202309125.
mla: Zens, Bettina, et al. “Lift-out Cryo-FIBSEM and Cryo-ET Reveal the Ultrastructural
Landscape of Extracellular Matrix.” Journal of Cell Biology, vol. 223,
no. 6, e202309125, Rockefeller University Press, 2024, doi:10.1083/jcb.202309125.
short: B. Zens, F. Fäßler, J. Hansen, R. Hauschild, J. Datler, V.-V. Hodirnau, V.
Zheden, J.H. Alanko, M.K. Sixt, F.K. Schur, Journal of Cell Biology 223 (2024).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: 'Representative tomograms containing the data shown in
Fig. 3, and Figs. S5 and S9 have been deposited in the Electron Microscopy Data
Bank under accession codes: EMD-18490, EMD-18491, EMD-18492, EMD-18493, and EMD-18494.
All tilt series, including frames, raw tilt series, and reconstructed IsoNet-filtered
tomograms, were deposited in the Electron Microscopy Public Image Archive database
under the accession code EMPIAR-11897.'
date_created: 2024-03-21T06:45:51Z
date_published: 2024-03-20T00:00:00Z
date_updated: 2026-10-01T11:24:27Z
day: '20'
ddc:
- '570'
department:
- _id: FlSc
- _id: MiSi
- _id: Bio
- _id: EM-Fac
doi: 10.1083/jcb.202309125
ec_funded: 1
external_id:
isi:
- '001264190100001'
pmid:
- '38506714'
file:
- access_level: open_access
checksum: 90d1984a93660735e506c2a304bc3f73
content_type: application/pdf
creator: dernst
date_created: 2024-03-25T12:52:04Z
date_updated: 2024-03-25T12:52:04Z
file_id: '15188'
file_name: 2024_JCB_Zens.pdf
file_size: 11907016
relation: main_file
success: 1
file_date_updated: 2024-03-25T12:52:04Z
fulldoi: https://doi.org/10.1083/jcb.202309125
has_accepted_license: '1'
intvolume: ' 223'
isi: 1
issue: '6'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
grant_number: P33367
name: Structure and isoform diversity of the Arp2/3 complex
- _id: 7bd318a1-9f16-11ee-852c-cc9217763180
grant_number: E435
name: In Situ Actin Structures via Hybrid Cryo-electron Microscopy
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
- _id: 059B463C-7A3F-11EA-A408-12923DDC885E
name: "NÃ\x96-Fonds Preis für die Jungforscherin des Jahres am IST Austria"
- _id: 2615199A-B435-11E9-9278-68D0E5697425
grant_number: '21317'
name: Spatiotemporal regulation of chemokine-induced signalling in leukocyte chemotaxis
- _id: 62909c6f-2b32-11ec-9570-e1476aab5308
grant_number: CZI01
name: CryoMinflux-guided in-situ visual proteomics and structure determination
publication: Journal of Cell Biology
publication_identifier:
eissn:
- 1540-8140
issn:
- 0021-9525
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular
matrix
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 223
year: '2024'
...
---
_id: '17463'
abstract:
- lang: eng
text: Allosteric modulation of protein function, wherein the binding of an effector
to a protein triggers conformational changes at distant functional sites, plays
a central part in the control of metabolism and cell signalling1,2,3. There has
been considerable interest in designing allosteric systems, both to gain insight
into the mechanisms underlying such ‘action at a distance’ modulation and to create
synthetic proteins whose functions can be regulated by effectors4,5,6,7. However,
emulating the subtle conformational changes distributed across many residues,
characteristic of natural allosteric proteins, is a significant challenge8,9.
Here, inspired by the classic Monod–Wyman–Changeux model of cooperativity10, we
investigate the de novo design of allostery through rigid-body coupling of peptide-switchable
hinge modules11 to protein interfaces12 that direct the formation of alternative
oligomeric states. We find that this approach can be used to generate a wide variety
of allosterically switchable systems, including cyclic rings that incorporate
or eject subunits in response to peptide binding and dihedral cages that undergo
effector-induced disassembly. Size-exclusion chromatography, mass photometry13
and electron microscopy reveal that these designed allosteric protein assemblies
closely resemble the design models in both the presence and absence of peptide
effectors and can have ligand-binding cooperativity comparable to classic natural
systems such as haemoglobin14. Our results indicate that allostery can arise from
global coupling of the energetics of protein substructures without optimized side-chain–side-chain
allosteric communication pathways and provide a roadmap for generating allosterically
triggerable delivery systems, protein nanomachines and cellular feedback control
circuitry.
acknowledgement: We thank D. D. Sahtoe, R. D. Kiber, Y. Hsia, N. Bethel and A. Favor
for helpful discussions and K. VanWormer and L. Goldschmidt for technical support.
We also thank X. Li and M. Lamb for mass spectrometry support. This work was supported
by the Washington Research Foundation Postdoctoral Fellowship (grant no. GR027504,
A. Pillai), a National Science Foundation Graduate Research Fellowship (grant no.
DGE-2140004, A.I.), a Human Frontier Science Program Long Term Fellowship (grant
no. LT000880/2019, F.P.), the Audacious Project at the Institute for Protein Design
(A.B., A. Pillai, A. Philomin, A.I. and D.B.), a National Energy Research Scientific
Computing Centre award (grant no. BER-ERCAP0022018), the Howard Hughes Medical Institute
(D.B.), the Open Philanthropy Project Improving Protein Design Fund (P.J.Y.L., C.D.
and D.B.) a gift from Microsoft (D.B.) and a grant from DARPA supporting the Harnessing
Enzymatic Activity for Lifesaving Remedies programme (grant no. HR001120S0052, contract
no. HR0011-21-2-0012, D.B.).
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Arvind
full_name: Pillai, Arvind
last_name: Pillai
- first_name: Abbas
full_name: Idris, Abbas
last_name: Idris
- first_name: Annika
full_name: Philomin, Annika
last_name: Philomin
- first_name: Connor
full_name: Weidle, Connor
last_name: Weidle
- first_name: Rebecca
full_name: Skotheim, Rebecca
last_name: Skotheim
- first_name: Philip J.Y.
full_name: Leung, Philip J.Y.
last_name: Leung
- first_name: Adam
full_name: Broerman, Adam
last_name: Broerman
- first_name: Cullen
full_name: Demakis, Cullen
last_name: Demakis
- first_name: Andrew J.
full_name: Borst, Andrew J.
last_name: Borst
- first_name: Florian M
full_name: Praetorius, Florian M
id: dfec9381-4341-11ee-8fd8-faa02bba7d62
last_name: Praetorius
orcid: 0000-0002-0806-8101
- first_name: David
full_name: Baker, David
last_name: Baker
citation:
ama: Pillai A, Idris A, Philomin A, et al. De novo design of allosterically switchable
protein assemblies. Nature. 2024;632:911–920. doi:10.1038/s41586-024-07813-2
apa: Pillai, A., Idris, A., Philomin, A., Weidle, C., Skotheim, R., Leung, P. J.
Y., … Baker, D. (2024). De novo design of allosterically switchable protein assemblies.
Nature. Springer Nature. https://doi.org/10.1038/s41586-024-07813-2
chicago: Pillai, Arvind, Abbas Idris, Annika Philomin, Connor Weidle, Rebecca Skotheim,
Philip J.Y. Leung, Adam Broerman, et al. “De Novo Design of Allosterically Switchable
Protein Assemblies.” Nature. Springer Nature, 2024. https://doi.org/10.1038/s41586-024-07813-2.
ieee: A. Pillai et al., “De novo design of allosterically switchable protein
assemblies,” Nature, vol. 632. Springer Nature, pp. 911–920, 2024.
ista: Pillai A, Idris A, Philomin A, Weidle C, Skotheim R, Leung PJY, Broerman A,
Demakis C, Borst AJ, Praetorius FM, Baker D. 2024. De novo design of allosterically
switchable protein assemblies. Nature. 632, 911–920.
mla: Pillai, Arvind, et al. “De Novo Design of Allosterically Switchable Protein
Assemblies.” Nature, vol. 632, Springer Nature, 2024, pp. 911–920, doi:10.1038/s41586-024-07813-2.
short: A. Pillai, A. Idris, A. Philomin, C. Weidle, R. Skotheim, P.J.Y. Leung, A.
Broerman, C. Demakis, A.J. Borst, F.M. Praetorius, D. Baker, Nature 632 (2024)
911–920.
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: All data are available either in the main text or as Supplementary
Information. PDB models and sequences for designs shown in main text figures are
available in the attached Supplementary Information, along with source data for
plots in main text figures. Structures determined by cryo-EM were deposited in the
PDB as 8UP1, 8URE and 8UTM, and maps were deposited in the EMDB under accession
numbers EMD-42442, EMD-42491 and EMD-42542.
date_created: 2024-08-25T22:01:08Z
date_published: 2024-08-22T00:00:00Z
date_updated: 2026-10-01T11:19:54Z
day: '22'
ddc:
- '570'
department:
- _id: FlPr
doi: 10.1038/s41586-024-07813-2
external_id:
isi:
- '001300534300019'
pmid:
- '39143214'
file:
- access_level: open_access
checksum: 39127601621a360ec0edc538627eb211
content_type: application/pdf
creator: dernst
date_created: 2024-09-09T12:01:14Z
date_updated: 2024-09-09T12:01:14Z
file_id: '18005'
file_name: 2024_Nature_Pillai.pdf
file_size: 16572040
relation: main_file
success: 1
file_date_updated: 2024-09-09T12:01:14Z
fulldoi: https://doi.org/10.1038/s41586-024-07813-2
has_accepted_license: '1'
intvolume: ' 632'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '911–920 '
pmid: 1
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes (supplementary data)
scopus_import: '1'
status: public
supplementarymaterial: yes
title: De novo design of allosterically switchable protein assemblies
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 632
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
_id: '18934'
abstract:
- lang: eng
text: The assembly of biomolecular condensate in eukaryotic cells and the accumulation
of amyloid deposits in neurons are processes involving the nucleation and growth
(NAG) of new protein phases. To therapeutically target protein phase separation,
drug candidates are tested in in vitro assays that monitor the increase in the
mass or size of the new phase. Limited mechanistic insight is, however, provided
if empirical or untestable kinetic models are fitted to these progress curves.
Here we present the web server NAGPKin that quantifies NAG rates using mass-based
or size-based progress curves as the input data. A report is generated containing
the fitted NAG parameters and elucidating the phase separation mechanisms at play.
The NAG parameters can be used to predict particle size distributions of, for
example, protein droplets formed by liquid-liquid phase separation (LLPS) or amyloid
fibrils formed by protein aggregation. Because minimal intervention is required
from the user, NAGPKin is a good platform for standardized reporting of LLPS and
protein self-assembly data. NAGPKin is useful for drug discovery as well as for
fundamental studies on protein phase separation. NAGPKin is freely available (no
login required) at https://nagpkin.i3s.up.pt .
acknowledgement: We thank Professor José Paulo Leal, Department of Computer Science
− Faculdade de Ciências da Universidade do Porto, for his invaluable help during
the Implementation of NAGPKin. This work is part of a project that has received
funding from the European Union’s Horizon 2020 research and innovation programme
under grant agreement no. 952334 (PhasAGE). This research was funded by the Portuguese
Foundation for Science and Technology (FCT) in the framework of project PTDC/QUI-COL/2444/2021.
article_number: mr1
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Zsuzsa
full_name: Sárkány, Zsuzsa
last_name: Sárkány
- first_name: Francisco
full_name: Figueiredo, Francisco
id: 8125cbe2-9661-11ed-a754-afe96018f37d
last_name: Figueiredo
- first_name: Sandra
full_name: Macedo-Ribeiro, Sandra
last_name: Macedo-Ribeiro
- first_name: Pedro M.
full_name: Martins, Pedro M.
last_name: Martins
citation:
ama: 'Sárkány Z, Figueiredo F, Macedo-Ribeiro S, Martins PM. NAGPKin: Nucleation-and-growth
parameters from the kinetics of protein phase separation. Molecular Biology
of the Cell. 2024;35(3). doi:10.1091/mbc.e23-07-0289'
apa: 'Sárkány, Z., Figueiredo, F., Macedo-Ribeiro, S., & Martins, P. M. (2024).
NAGPKin: Nucleation-and-growth parameters from the kinetics of protein phase separation.
Molecular Biology of the Cell. American Society for Cell Biology. https://doi.org/10.1091/mbc.e23-07-0289'
chicago: 'Sárkány, Zsuzsa, Francisco Figueiredo, Sandra Macedo-Ribeiro, and Pedro
M. Martins. “NAGPKin: Nucleation-and-Growth Parameters from the Kinetics of Protein
Phase Separation.” Molecular Biology of the Cell. American Society for
Cell Biology, 2024. https://doi.org/10.1091/mbc.e23-07-0289.'
ieee: 'Z. Sárkány, F. Figueiredo, S. Macedo-Ribeiro, and P. M. Martins, “NAGPKin:
Nucleation-and-growth parameters from the kinetics of protein phase separation,”
Molecular Biology of the Cell, vol. 35, no. 3. American Society for Cell
Biology, 2024.'
ista: 'Sárkány Z, Figueiredo F, Macedo-Ribeiro S, Martins PM. 2024. NAGPKin: Nucleation-and-growth
parameters from the kinetics of protein phase separation. Molecular Biology of
the Cell. 35(3), mr1.'
mla: 'Sárkány, Zsuzsa, et al. “NAGPKin: Nucleation-and-Growth Parameters from the
Kinetics of Protein Phase Separation.” Molecular Biology of the Cell, vol.
35, no. 3, mr1, American Society for Cell Biology, 2024, doi:10.1091/mbc.e23-07-0289.'
short: Z. Sárkány, F. Figueiredo, S. Macedo-Ribeiro, P.M. Martins, Molecular Biology
of the Cell 35 (2024).
das_tickbox: '0'
date_created: 2025-01-29T07:58:40Z
date_published: 2024-03-01T00:00:00Z
date_updated: 2026-10-01T11:22:53Z
day: '01'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1091/mbc.e23-07-0289
external_id:
pmid:
- '38117593'
file:
- access_level: open_access
checksum: d7deb6390f294da69321cfbe352ed611
content_type: application/pdf
creator: dernst
date_created: 2025-01-29T08:12:11Z
date_updated: 2025-01-29T08:12:11Z
file_id: '18935'
file_name: 2024_MolecularBioCell_Sarkany.pdf
file_size: 1699180
relation: main_file
success: 1
file_date_updated: 2025-01-29T08:12:11Z
fulldoi: https://doi.org/10.1091/mbc.e23-07-0289
has_accepted_license: '1'
intvolume: ' 35'
issue: '3'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: Molecular Biology of the Cell
publication_identifier:
eissn:
- 1939-4586
issn:
- 1059-1524
publication_status: published
publisher: American Society for Cell Biology
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: no
title: 'NAGPKin: Nucleation-and-growth parameters from the kinetics of protein phase
separation'
tmp:
image: /images/cc_by_nc_sa.png
legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
BY-NC-SA 4.0)
short: CC BY-NC-SA (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 35
year: '2024'
...