---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '17468'
abstract:
- lang: eng
text: Oxygen redox chemistry is central to life1 and many human-made technologies,
such as in energy storage2,3,4. The large energy gain from oxygen redox reactions
is often connected with the occurrence of harmful reactive oxygen species3,5,6.
Key species are superoxide and the highly reactive singlet oxygen3,4,5,6,7, which
may evolve from superoxide. However, the factors determining the formation of
singlet oxygen, rather than the relatively unreactive triplet oxygen, are unknown.
Here we report that the release of triplet or singlet oxygen is governed by individual
Marcus normal and inverted region behaviour. We found that as the driving force
for the reaction increases, the initially dominant evolution of triplet oxygen
slows down, and singlet oxygen evolution becomes predominant with higher maximum
kinetics. This behaviour also applies to the widely observed superoxide disproportionation,
in which one superoxide is oxidized by another, in both non-aqueous and aqueous
systems, with Lewis and Brønsted acidity controlling the driving forces. Singlet
oxygen yields governed by these conditions are relevant, for example, in batteries
or cellular organelles in which superoxide forms. Our findings suggest ways to
understand and control spin states and kinetics in oxygen redox chemistry, with
implications for fields, including life sciences, pure chemistry and energy storage.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: ScienComp
acknowledgement: S.A.F. thanks the Institute of Science and Technology Austria (ISTA)
for the support. The Scientific Service Units of ISTA supported this research through
resources provided by the Imaging and Optics Facility, the Lab Support Facility,
the Miba Machine Shop and Scientific Computing. This research was partly funded
by the Austrian Science Fund (FWF) (10.55776/P37169 and 10.55776/COE5). For open
access purposes, the author has applied for a CC BY public copyright licence to
any author-accepted manuscript version arising from this submission. R.H. acknowledges
funding through CZI grant DAF2020-225401 (10.37921/120055ratwvi) from the Chan Zuckerberg
Initiative DAF, an advised fund of Silicon Valley Community Foundation (10.13039/100014989).
H.T.K.N. acknowledges funding by the European Commission Erasmus Mundus Joint Masters
programme. We thank M. Sixt and M. Chinon for the discussions about O-redox in life
and R. Jethwa for proofreading. Open access funding was provided by ISTA.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Soumyadip
full_name: Mondal, Soumyadip
id: d25d21ef-dc8d-11ea-abe3-ec4576307f48
last_name: Mondal
- first_name: Huyen T.K.
full_name: Nguyen, Huyen T.K.
last_name: Nguyen
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Stefan Alexander
full_name: Freunberger, Stefan Alexander
id: A8CA28E6-CE23-11E9-AD2D-EC27E6697425
last_name: Freunberger
orcid: 0000-0003-2902-5319
citation:
ama: Mondal S, Nguyen HTK, Hauschild R, Freunberger SA. Marcus kinetics control
singlet and triplet oxygen evolving from superoxide. Nature. 2025;646(8085):601–605.
doi:10.1038/s41586-025-09587-7
apa: Mondal, S., Nguyen, H. T. K., Hauschild, R., & Freunberger, S. A. (2025).
Marcus kinetics control singlet and triplet oxygen evolving from superoxide. Nature.
Springer Nature. https://doi.org/10.1038/s41586-025-09587-7
chicago: Mondal, Soumyadip, Huyen T.K. Nguyen, Robert Hauschild, and Stefan Alexander
Freunberger. “Marcus Kinetics Control Singlet and Triplet Oxygen Evolving from
Superoxide.” Nature. Springer Nature, 2025. https://doi.org/10.1038/s41586-025-09587-7.
ieee: S. Mondal, H. T. K. Nguyen, R. Hauschild, and S. A. Freunberger, “Marcus kinetics
control singlet and triplet oxygen evolving from superoxide,” Nature, vol.
646, no. 8085. Springer Nature, pp. 601–605, 2025.
ista: Mondal S, Nguyen HTK, Hauschild R, Freunberger SA. 2025. Marcus kinetics control
singlet and triplet oxygen evolving from superoxide. Nature. 646(8085), 601–605.
mla: Mondal, Soumyadip, et al. “Marcus Kinetics Control Singlet and Triplet Oxygen
Evolving from Superoxide.” Nature, vol. 646, no. 8085, Springer Nature,
2025, pp. 601–605, doi:10.1038/s41586-025-09587-7.
short: S. Mondal, H.T.K. Nguyen, R. Hauschild, S.A. Freunberger, Nature 646 (2025)
601–605.
corr_author: '1'
date_created: 2024-08-29T10:40:23Z
date_published: 2025-10-16T00:00:00Z
date_updated: 2026-04-28T13:18:33Z
day: '16'
ddc:
- '540'
department:
- _id: StFr
- _id: Bio
doi: 10.1038/s41586-025-09587-7
external_id:
isi:
- '001586378900001'
pmid:
- '41044415'
file:
- access_level: open_access
checksum: b507ddd23df0388aa65d04dc9b00fe3d
content_type: application/pdf
creator: dernst
date_created: 2025-10-20T10:26:13Z
date_updated: 2025-10-20T10:26:13Z
file_id: '20500'
file_name: 2025_Nature_Mondal.pdf
file_size: 3809247
relation: main_file
success: 1
file_date_updated: 2025-10-20T10:26:13Z
has_accepted_license: '1'
intvolume: ' 646'
isi: 1
issue: '8085'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: 601–605
pmid: 1
project:
- _id: 8df062be-16d5-11f0-9cad-f559b6612c7e
grant_number: P37169
name: Singlet oxygen in non-aqueous oxygen redox chemistry
- _id: c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473
grant_number: CZI01
name: Tools for automation and feedback microscopy
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
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/taming-the-bad-oxygen/
scopus_import: '1'
status: public
title: Marcus kinetics control singlet and triplet oxygen evolving from superoxide
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 646
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20082'
abstract:
- lang: eng
text: Efficient immune responses rely on the capacity of leukocytes to traverse
diverse and complex tissues. To meet such changing environmental conditions, leukocytes
usually adopt an ameboid configuration, using their forward-positioned nucleus
as a probe to identify and follow the path of least resistance among pre-existing
pores. We show that, in dense environments where even the largest pores preclude
free passage, leukocytes position their nucleus behind the centrosome and organelles.
The local compression imposed on the cell body by its surroundings triggers assembly
of a central F-actin pool, located between cell front and nucleus. Central actin
pushes outward to transiently dilate a path for organelles and nucleus. Pools
of central and front actin are tightly coupled and experimental depletion of the
central pool enhances actin accumulation and protrusion formation at the cell
front. Although this shifted balance speeds up cells in permissive environments,
migration in restrictive environments is impaired, as the unleashed leading edge
dissociates from the trapped cell body. Our findings establish an actin regulatory
loop that balances path dilation with advancement of the leading edge to maintain
cellular coherence.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: This research was supported by the Scientific Service Units of ISTA
through resources provided by the Imaging and Optics, Preclinical and Lab Support
Facilities. In particular, we thank M. A. Symth and F. G. G. Leite, from the Virus
Service Team, who helped generating the lentiviral particles used in this study.
We thank all the members of the Sixt group for valuable discussions and feedback,
in particular, I. Mayer, for helping with T cell isolation and Z. (P.) Li for providing
the Actin–GFP DC line. We are also thankful to J. Mandl and C. Shen for their feedback
during the writing of this manuscript. This work was supported by a European Research
Council grant ERC-SyG 101071793 to M.S. M.J.A. was supported by an HFSP Postdoctoral
Fellowship LTF 177 2021 and A.J.G. by a Lise Meitner Fellowship of the FWF (Austrian
Science Fund). Y.F. was supported by the AMED-CREST (JP19gm1310005), the Medical
Research Center Initiative for High Depth Omics and CURE:JPMXP1323015486 for MIB,
Kyushu University. Open access funding provided by Institute of Science and Technology
(IST Austria).
article_processing_charge: Yes (via OA deal)
article_type: letter_note
author:
- first_name: Patricia
full_name: Dos Reis Rodrigues, Patricia
id: 26E95904-5160-11E9-9C0B-C5B0DC97E90F
last_name: Dos Reis Rodrigues
orcid: 0000-0003-1681-508X
- first_name: Mario
full_name: Avellaneda Sarrió, Mario
id: DC4BA84C-56E6-11EA-AD5D-348C3DDC885E
last_name: Avellaneda Sarrió
orcid: 0000-0001-6406-524X
- first_name: Nikola
full_name: Canigova, Nikola
id: 3795523E-F248-11E8-B48F-1D18A9856A87
last_name: Canigova
orcid: 0000-0002-8518-5926
- 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: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Yoshinori
full_name: Fukui, Yoshinori
last_name: Fukui
- first_name: Alba
full_name: Juanes Garcia, Alba
id: 40F05888-F248-11E8-B48F-1D18A9856A87
last_name: Juanes Garcia
orcid: 0000-0002-1009-9652
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Dos Reis Rodrigues P, Avellaneda Sarrió M, Canigova N, et al. Migrating immune
cells globally coordinate protrusive forces. Nature Immunology. 2025;26:1258–1266.
doi:10.1038/s41590-025-02211-w
apa: Dos Reis Rodrigues, P., Avellaneda Sarrió, M., Canigova, N., Gärtner, F. R.,
Vaahtomeri, K., Riedl, M., … Sixt, M. K. (2025). Migrating immune cells globally
coordinate protrusive forces. Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-025-02211-w
chicago: Dos Reis Rodrigues, Patricia, Mario Avellaneda Sarrió, Nikola Canigova,
Florian R Gärtner, Kari Vaahtomeri, Michael Riedl, Ingrid de Vries, et al. “Migrating
Immune Cells Globally Coordinate Protrusive Forces.” Nature Immunology.
Springer Nature, 2025. https://doi.org/10.1038/s41590-025-02211-w.
ieee: P. Dos Reis Rodrigues et al., “Migrating immune cells globally coordinate
protrusive forces,” Nature Immunology, vol. 26. Springer Nature, pp. 1258–1266,
2025.
ista: Dos Reis Rodrigues P, Avellaneda Sarrió M, Canigova N, Gärtner FR, Vaahtomeri
K, Riedl M, de Vries I, Merrin J, Hauschild R, Fukui Y, Juanes Garcia A, Sixt
MK. 2025. Migrating immune cells globally coordinate protrusive forces. Nature
Immunology. 26, 1258–1266.
mla: Dos Reis Rodrigues, Patricia, et al. “Migrating Immune Cells Globally Coordinate
Protrusive Forces.” Nature Immunology, vol. 26, Springer Nature, 2025,
pp. 1258–1266, doi:10.1038/s41590-025-02211-w.
short: P. Dos Reis Rodrigues, M. Avellaneda Sarrió, N. Canigova, F.R. Gärtner, K.
Vaahtomeri, M. Riedl, I. de Vries, J. Merrin, R. Hauschild, Y. Fukui, A. Juanes
Garcia, M.K. Sixt, Nature Immunology 26 (2025) 1258–1266.
corr_author: '1'
date_created: 2025-07-27T22:01:26Z
date_published: 2025-08-01T00:00:00Z
date_updated: 2026-04-28T13:26:50Z
day: '01'
ddc:
- '570'
department:
- _id: MiSi
- _id: NanoFab
- _id: Bio
doi: 10.1038/s41590-025-02211-w
external_id:
isi:
- '001529134300001'
pmid:
- '40664976'
file:
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checksum: 0c725123dca7797c682609bff2c4c5ac
content_type: application/pdf
creator: dernst
date_created: 2025-07-31T08:00:33Z
date_updated: 2025-07-31T08:00:33Z
file_id: '20096'
file_name: 2025_NatureImmunology_ReisRodrigues.pdf
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intvolume: ' 26'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 1258–1266
pmid: 1
project:
- _id: bd91e723-d553-11ed-ba76-fe7eeb2185fd
grant_number: '101071793'
name: 'Pushing from within: Control of cell shape, integrity and motility by cytoskeletal
pushing forces'
- _id: c092d618-5a5b-11eb-8a69-f92e1e843fc8
grant_number: 944-2020
name: 'Bioelectric patrolling: the role of the local membrane potential in immune
cell migration'
publication: Nature Immunology
publication_identifier:
eissn:
- 1529-2916
issn:
- 1529-2908
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/bench-pressing-cells/
record:
- id: '20149'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Migrating immune cells globally coordinate protrusive forces
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 26
year: '2025'
...
---
OA_place: publisher
_id: '20149'
abstract:
- lang: eng
text: "Immune responses depend on the coordinated and efficient migration of leukocytes.
These\r\ncells, which are embedded and tightly confined within tissues, must navigate
and traverse\r\ndiverse and complex three-dimensional environments. Leukocytes
adapt their locomotory\r\nbehavior to the mechanical, geometrical, and biochemical
characteristics of their\r\nsurroundings. In low-density environments, where the
pore size of the interstitial matrix\r\nallows free passage, these cells position
the nucleus directly behind the lamellipodium, the\r\nprotrusive actin structure
that forms the leading front of the cell. In this configuration, they\r\nuse the
nucleus as a gauge to identify the path of least resistance.\r\nHere, we show
that in high-density environments, where the pore size precludes free passage\r\nof
the cell body, leukocytes reposition the microtubule-organizing center (MTOC)
and\r\nassociated organelles in front of the nucleus. In this configuration, they
use actin structures\r\nprotruding orthogonally to the direction of migration
in order to open a path for the cell body.\r\nWe identify two distinct actin populations
that serve this purpose at different subcellular\r\nlocalizations. At the leading
edge, local indentation of the plasma membrane leads to\r\nrecruitment of the
Wiskott-Aldrich syndrome protein (WASp), which, via Arp2/3, results in\r\nthe
formation of individual actin foci. At the cell body, actin polymerization is
triggered by\r\nDOCK8, a Cdc42 exchange factor, resulting in the formation of
a central actin pool.\r\nWe demonstrate that the central and peripheral actin
pools are functionally communicating\r\nand that depletion of the central actin
pool leads to increased actin accumulation at the cell\r\nfront, resulting in
excessive extension of the leading edge."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: NanoFab
acknowledgement: "I would like to acknowledge the\r\nfinancial support of the European
Research Council through the ERC-SyG grant “Pushing from\r\nwithin: Control of cell
shape, integrity and motility by cytoskeletal pushing forces”\r\n(01071793), which
made this research possible. "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Patricia
full_name: Dos Reis Rodrigues, Patricia
id: 26E95904-5160-11E9-9C0B-C5B0DC97E90F
last_name: Dos Reis Rodrigues
orcid: 0000-0003-1681-508X
citation:
ama: Dos Reis Rodrigues P. Coordination of protrusive forces in immune cell migration
. 2025. doi:10.15479/AT-ISTA-20149
apa: Dos Reis Rodrigues, P. (2025). Coordination of protrusive forces in immune
cell migration . Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20149
chicago: Dos Reis Rodrigues, Patricia. “Coordination of Protrusive Forces in Immune
Cell Migration .” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-20149.
ieee: P. Dos Reis Rodrigues, “Coordination of protrusive forces in immune cell migration
,” Institute of Science and Technology Austria, 2025.
ista: Dos Reis Rodrigues P. 2025. Coordination of protrusive forces in immune cell
migration . Institute of Science and Technology Austria.
mla: Dos Reis Rodrigues, Patricia. Coordination of Protrusive Forces in Immune
Cell Migration . Institute of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-20149.
short: P. Dos Reis Rodrigues, Coordination of Protrusive Forces in Immune Cell Migration
, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-08-08T09:18:02Z
date_published: 2025-08-08T00:00:00Z
date_updated: 2026-04-28T13:26:50Z
day: '08'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: MiSi
doi: 10.15479/AT-ISTA-20149
file:
- access_level: open_access
checksum: fda8a1070667c3562263f4867609b41b
content_type: application/pdf
creator: prodrigu
date_created: 2025-08-27T12:59:10Z
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file_size: 63885565
relation: main_file
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creator: prodrigu
date_created: 2025-08-27T13:00:30Z
date_updated: 2025-08-27T13:02:28Z
file_id: '20233'
file_name: 2025_ReisRodrigues_Patricia_Thesis.docx
file_size: 50483434
relation: source_file
file_date_updated: 2025-08-27T13:02:28Z
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '114'
project:
- _id: bd91e723-d553-11ed-ba76-fe7eeb2185fd
grant_number: '101071793'
name: 'Pushing from within: Control of cell shape, integrity and motility by cytoskeletal
pushing forces'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '10703'
relation: part_of_dissertation
status: public
- id: '20082'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
title: 'Coordination of protrusive forces in immune cell migration '
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
OA_place: repository
OA_type: gold
_id: '18697'
abstract:
- lang: eng
text: The information-processing capability of the brain’s cellular network depends
on the physical wiring pattern between neurons and their molecular and functional
characteristics. Mapping neurons and resolving their individual synaptic connections
can be achieved by volumetric imaging at nanoscale resolution with dense cellular
labelling. Light microscopy is uniquely positioned to visualize specific molecules
but dense, synapse-level circuit reconstruction by light microscopy has been out
of reach due to limitations in resolution, contrast, and volumetric imaging capability.
Here we developed light-microscopy based connectomics (LICONN). We integrated
specifically engineered hydrogel embedding and expansion with comprehensive deep-learning
based segmentation and analysis of connectivity, thus directly incorporating molecular
information in synapse-level brain tissue reconstructions. LICONN will allow synapse-level
brain tissue phenotyping in biological experiments in a readily adoptable manner.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: ScienComp
- _id: PreCl
- _id: M-Shop
- _id: E-Lib
article_processing_charge: No
author:
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
citation:
ama: Danzl JG, Lyudchik J, Kreuzinger C. Light-microscopy based connectomic reconstruction
of mammalian brain tissue. 2025. doi:10.15479/AT:ISTA:18697
apa: Danzl, J. G., Lyudchik, J., & Kreuzinger, C. (2025). Light-microscopy based
connectomic reconstruction of mammalian brain tissue. Institute of Science and
Technology Austria. https://doi.org/10.15479/AT:ISTA:18697
chicago: Danzl, Johann G, Julia Lyudchik, and Caroline Kreuzinger. “Light-Microscopy
Based Connectomic Reconstruction of Mammalian Brain Tissue.” Institute of Science
and Technology Austria, 2025. https://doi.org/10.15479/AT:ISTA:18697.
ieee: J. G. Danzl, J. Lyudchik, and C. Kreuzinger, “Light-microscopy based connectomic
reconstruction of mammalian brain tissue.” Institute of Science and Technology
Austria, 2025.
ista: Danzl JG, Lyudchik J, Kreuzinger C. 2025. Light-microscopy based connectomic
reconstruction of mammalian brain tissue, Institute of Science and Technology
Austria, 10.15479/AT:ISTA:18697.
mla: Danzl, Johann G., et al. Light-Microscopy Based Connectomic Reconstruction
of Mammalian Brain Tissue. Institute of Science and Technology Austria, 2025,
doi:10.15479/AT:ISTA:18697.
short: J.G. Danzl, J. Lyudchik, C. Kreuzinger, (2025).
contributor:
- contributor_type: researcher
first_name: Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- contributor_type: researcher
first_name: Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- contributor_type: researcher
first_name: Michal
last_name: Januszewski
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success: 1
file_date_updated: 2025-02-28T16:50:39Z
has_accepted_license: '1'
month: '03'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
link:
- description: Original datasets of large size (>10GB) and datasets in zarr/n5/ims/npz
format are provided via this external link.
relation: research_data
url: https://pub.ista.ac.at/group_danzl/data/LICONN/
record:
- id: '19704'
relation: used_in_publication
status: public
status: public
title: Light-microscopy based connectomic reconstruction of mammalian brain tissue
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: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '19704'
abstract:
- lang: eng
text: The information-processing capability of the brain’s cellular network depends
on the physical wiring pattern between neurons and their molecular and functional
characteristics. Mapping neurons and resolving their individual synaptic connections
can be achieved by volumetric imaging at nanoscale resolution1,2 with dense cellular
labelling. Light microscopy is uniquely positioned to visualize specific molecules,
but dense, synapse-level circuit reconstruction by light microscopy has been out
of reach, owing to limitations in resolution, contrast and volumetric imaging
capability. Here we describe light-microscopy-based connectomics (LICONN). We
integrated specifically engineered hydrogel embedding and expansion with comprehensive
deep-learning-based segmentation and analysis of connectivity, thereby directly
incorporating molecular information into synapse-level reconstructions of brain
tissue. LICONN will allow synapse-level phenotyping of brain tissue in biological
experiments in a readily adoptable manner.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: ScienComp
- _id: PreCl
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank S. Dorkenwald and P. Li for critical reading of the manuscript,
S. Loomba for discussions and E. Miguel for support with data handling. We acknowledge
support from ISTA’s scientific service units: Imaging and Optics, Lab Support, Scientific
Computing, the preclinical facility, the Miba Machine Shop and the library. We acknowledge
funding from the following sources: Austrian Science Fund (FWF) grant DK W1232 (J.G.D.
and M.R.T.); Austrian Academy of Sciences DOC fellowship 26137 (M.R.T.); Gesellschaft
für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); the European Union’s
Horizon 2020 research and innovation programme and Marie Skłodowska-Curie Actions
Fellowship 665385 (J.L.); and the European Union’s Horizon 2020 research and innovation
programme and European Research Council (ERC) grant 101044865 ‘SecretAutism’ (G.N.).Open
access funding provided by Institute of Science and Technology (IST Austria).'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Michał
full_name: Januszewski, Michał
last_name: Januszewski
- first_name: Vitali
full_name: Vistunou, Vitali
id: 7e146587-8972-11ed-ae7b-d7a32ea86a81
last_name: Vistunou
- first_name: Nathalie
full_name: Agudelo Duenas, Nathalie
id: 40E7F008-F248-11E8-B48F-1D18A9856A87
last_name: Agudelo Duenas
- first_name: Jakob
full_name: Vorlaufer, Jakob
id: 937696FA-C996-11E9-8C7C-CF13E6697425
last_name: Vorlaufer
orcid: 0009-0000-7590-3501
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
- first_name: Bárbara
full_name: Oliveira, Bárbara
id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
last_name: Oliveira
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Viren
full_name: Jain, Viren
last_name: Jain
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy-based connectomic
reconstruction of mammalian brain tissue. Nature. 2025;642:398-410. doi:10.1038/s41586-025-08985-1
apa: Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas,
N., Vorlaufer, J., … Danzl, J. G. (2025). Light-microscopy-based connectomic reconstruction
of mammalian brain tissue. Nature. Springer Nature. https://doi.org/10.1038/s41586-025-08985-1
chicago: Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou,
Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy-Based
Connectomic Reconstruction of Mammalian Brain Tissue.” Nature. Springer
Nature, 2025. https://doi.org/10.1038/s41586-025-08985-1.
ieee: M. Tavakoli et al., “Light-microscopy-based connectomic reconstruction
of mammalian brain tissue,” Nature, vol. 642. Springer Nature, pp. 398–410,
2025.
ista: Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer
J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl
JG. 2025. Light-microscopy-based connectomic reconstruction of mammalian brain
tissue. Nature. 642, 398–410.
mla: Tavakoli, Mojtaba, et al. “Light-Microscopy-Based Connectomic Reconstruction
of Mammalian Brain Tissue.” Nature, vol. 642, Springer Nature, 2025, pp.
398–410, doi:10.1038/s41586-025-08985-1.
short: M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas,
J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino,
V. Jain, J.G. Danzl, Nature 642 (2025) 398–410.
corr_author: '1'
date_created: 2025-05-18T22:02:51Z
date_published: 2025-06-12T00:00:00Z
date_updated: 2026-04-28T13:33:34Z
day: '12'
ddc:
- '570'
department:
- _id: JoDa
- _id: GradSch
- _id: Bio
- _id: GaNo
doi: 10.1038/s41586-025-08985-1
ec_funded: 1
external_id:
isi:
- '001483477000001'
pmid:
- '40335689'
file:
- access_level: open_access
checksum: ebc99d7108e728f46db0a009292675ef
content_type: application/pdf
creator: dernst
date_created: 2025-07-03T06:55:20Z
date_updated: 2025-07-03T06:55:20Z
file_id: '19959'
file_name: 2025_Nature_Tavakoli.pdf
file_size: 133201290
relation: main_file
success: 1
file_date_updated: 2025-07-03T06:55:20Z
has_accepted_license: '1'
intvolume: ' 642'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 398-410
pmid: 1
project:
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
grant_number: '26137'
name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
Microscopy
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6
grant_number: '101044865'
name: Toward an understanding of the brain interstitial system and the extracellular
proteome in health and autism spectrum disorders
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
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/piecing-together-the-brain-puzzle/
record:
- id: '18677'
relation: earlier_version
status: public
- id: '18697'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Light-microscopy-based connectomic reconstruction of mammalian brain tissue
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 642
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '19602'
abstract:
- lang: eng
text: N4-methylcytosine (4mC) is an important DNA modification in prokaryotes, but
its relevance and even its presence in eukaryotes have been mysterious. Here we
show that spermatogenesis in the liverwort Marchantia polymorpha involves two
waves of extensive DNA methylation reprogramming. First, 5-methylcytosine (5mC)
expands from transposons to the entire genome. Notably, the second wave installs
4mC throughout genic regions, covering over 50% of CG sites in sperm. 4mC requires
a methyltransferase (MpDN4MT1a) that is specifically expressed during late spermiogenesis.
Deletion of MpDN4MT1a alters the sperm transcriptome, causes sperm swimming and
fertility defects, and impairs post-fertilization development. Our results reveal
extensive 4mC in a eukaryote, identify a family of eukaryotic methyltransferases,
and elucidate the biological functions of 4mC in reproductive development, thereby
expanding the repertoire of functional eukaryotic DNA modifications.
acknowledged_ssus:
- _id: Bio
- _id: ScienComp
acknowledgement: We thank Sir Richard Roberts (NEB) for the kind gift of anti-4mC
antibodies. We are also grateful to the JIC Small Molecule Mass Spectrometry (Lionel
Hill) and Chemistry (Martin Rejzek) platforms as well as the High Resolution Metabolomics
Laboratory (Manfred Beckmann, Aberystwyth University) for their assistance with
LC-MS. Additionally, we acknowledge the assistance of the JIC Bioimaging Facility
and ISTA Imaging and Optics Facility for microscopy. Finally, we appreciate the
High Performance Computing resources provided by the ISTA Scientific Computing Facility
and Norwich BioScience Institute Partnership Computing Infrastructure. This work
was funded by a Sainsbury Charitable Foundation studentship (J.W.), a UKRI-BBSRC
Doctoral Training Partnerships studentship (BBT0087171 to J.T.), a European Research
Council Starting Grant (“SexMeth” 804981 to J.W., S.X., and X.F.), two Biotechnology
and Biological Sciences Research Council (BBSRC) grants (BBS0096201 and BBP0135111
to J.Z., M.V., and X.F.), an EMBO Long Term Fellowship (Y.L.), an ISTA Bridge Fellowship
(S.X.), and ISTA core funding (Y.Y. and X.F.).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: James
full_name: Walker, James
last_name: Walker
- first_name: Jingyi
full_name: Zhang, Jingyi
last_name: Zhang
- first_name: Yalin
full_name: Liu, Yalin
last_name: Liu
- first_name: Shujuan
full_name: Xu, Shujuan
id: 9724dd9d-f591-11ee-bd51-e97ed0652286
last_name: Xu
- first_name: Yiming
full_name: Yu, Yiming
id: 318e643b-8b61-11ed-b69e-aafa103ec8dd
last_name: Yu
orcid: 0000-0002-9919-7282
- first_name: Martin
full_name: Vickers, Martin
last_name: Vickers
- first_name: Weizhi
full_name: Ouyang, Weizhi
id: fec73395-8b60-11ed-b69e-927fda99c743
last_name: Ouyang
- first_name: Judit
full_name: Tálas, Judit
last_name: Tálas
- first_name: Liam
full_name: Dolan, Liam
last_name: Dolan
- first_name: Keiji
full_name: Nakajima, Keiji
last_name: Nakajima
- first_name: Xiaoqi
full_name: Feng, Xiaoqi
id: e0164712-22ee-11ed-b12a-d80fcdf35958
last_name: Feng
orcid: 0000-0002-4008-1234
citation:
ama: Walker J, Zhang J, Liu Y, et al. Extensive N4 cytosine methylation is essential
for Marchantia sperm function. Cell. 2025;188(11):2890-2906.e14. doi:10.1016/j.cell.2025.03.014
apa: Walker, J., Zhang, J., Liu, Y., Xu, S., Yu, Y., Vickers, M., … Feng, X. (2025).
Extensive N4 cytosine methylation is essential for Marchantia sperm function.
Cell. Elsevier. https://doi.org/10.1016/j.cell.2025.03.014
chicago: Walker, James, Jingyi Zhang, Yalin Liu, Shujuan Xu, Yiming Yu, Martin Vickers,
Weizhi Ouyang, et al. “Extensive N4 Cytosine Methylation Is Essential for Marchantia
Sperm Function.” Cell. Elsevier, 2025. https://doi.org/10.1016/j.cell.2025.03.014.
ieee: J. Walker et al., “Extensive N4 cytosine methylation is essential for
Marchantia sperm function,” Cell, vol. 188, no. 11. Elsevier, p. 2890–2906.e14,
2025.
ista: Walker J, Zhang J, Liu Y, Xu S, Yu Y, Vickers M, Ouyang W, Tálas J, Dolan
L, Nakajima K, Feng X. 2025. Extensive N4 cytosine methylation is essential for
Marchantia sperm function. Cell. 188(11), 2890–2906.e14.
mla: Walker, James, et al. “Extensive N4 Cytosine Methylation Is Essential for Marchantia
Sperm Function.” Cell, vol. 188, no. 11, Elsevier, 2025, p. 2890–2906.e14,
doi:10.1016/j.cell.2025.03.014.
short: J. Walker, J. Zhang, Y. Liu, S. Xu, Y. Yu, M. Vickers, W. Ouyang, J. Tálas,
L. Dolan, K. Nakajima, X. Feng, Cell 188 (2025) 2890–2906.e14.
corr_author: '1'
date_created: 2025-04-20T22:01:28Z
date_published: 2025-05-29T00:00:00Z
date_updated: 2026-04-28T13:36:51Z
day: '29'
ddc:
- '570'
department:
- _id: XiFe
doi: 10.1016/j.cell.2025.03.014
ec_funded: 1
external_id:
isi:
- '001504744800006'
pmid:
- '40209706'
file:
- access_level: open_access
checksum: 0dcc2feb368dfe7c4890093366b2dacb
content_type: application/pdf
creator: dernst
date_created: 2025-12-29T13:40:32Z
date_updated: 2025-12-29T13:40:32Z
file_id: '20871'
file_name: 2025_Cell_Walker.pdf
file_size: 11622960
relation: main_file
success: 1
file_date_updated: 2025-12-29T13:40:32Z
has_accepted_license: '1'
intvolume: ' 188'
isi: 1
issue: '11'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: 2890-2906.e14
pmid: 1
project:
- _id: bdb51a6e-d553-11ed-ba76-c2025f3d5725
call_identifier: H2020
grant_number: '804981'
name: Establishment, modulation and inheritance of sexual lineage specific DNA methylation
in plants
publication: Cell
publication_identifier:
eissn:
- 1097-4172
issn:
- 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/from-bacterial-immunity-to-plant-sex/
scopus_import: '1'
status: public
title: Extensive N4 cytosine methylation is essential for Marchantia sperm function
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 188
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '19421'
abstract:
- lang: eng
text: The phytohormone auxin (Aux) is a principal endogenous developmental signal
in plants. It mediates transcriptional reprogramming by a well-established canonical
signalling mechanism. TIR1/AFB auxin receptors are F-box subunits of an ubiquitin
ligase complex; after auxin perception, they associate with Aux/IAA transcriptional
repressors and ubiquitinate them for degradation, thus enabling the activation
of auxin response factor (ARF) transcription factors1,2,3. Here we revise this
paradigm by showing that without TIR1 adenylate cyclase (AC) activity4, auxin-induced
degradation of Aux/IAAs is not sufficient to mediate the transcriptional auxin
response. Abolishing the TIR1 AC activity does not affect auxin-induced degradation
of Aux/IAAs but renders TIR1 non-functional in mediating transcriptional reprogramming
and auxin-regulated development, including shoot, root, root hair growth and lateral
root formation. Transgenic plants show that local cAMP production in the vicinity
of the Aux/IAA–ARF complex by unrelated AC enzymes bypasses the need for auxin
perception and is sufficient to induce ARF-mediated transcription. These discoveries
revise the canonical model of auxin signalling and establish TIR1/AFB-produced
cAMP as a second messenger essential for transcriptional reprograming.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
acknowledgement: We are grateful to J. Callis and H.-Q. Yang for sharing materials
and to M. Estelle and S. Kepinski for inspiring discussions. This research was supported
by the Laboratory Support Facility, the Plant Facility and the Imaging and Optics
Facility of the Institute of Science and Technology Austria. This project has received
funding from the European Research Council (101142681 CYNIPS) and Austrian Science
Fund (P 37051-B). L.Q. was supported by the National Natural Science Foundation
of China (grant no. 32470327). M.Z. was supported by the Interdisciplinary Project
Committee of the Institute of Science and Technology Austria, and Y.P. was supported
by an EMBO Postdoctoral Fellowship (ALTF 38-2023). Open access funding provided
by Institute of Science and Technology (IST Austria).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Huihuang
full_name: Chen, Huihuang
id: 83c96512-15b2-11ec-abd3-b7eede36184f
last_name: Chen
- first_name: Linlin
full_name: Qi, Linlin
id: 44B04502-A9ED-11E9-B6FC-583AE6697425
last_name: Qi
orcid: 0000-0001-5187-8401
- first_name: Minxia
full_name: Zou, Minxia
id: 5c243f41-03f3-11ec-841c-96faf48a7ef9
last_name: Zou
- first_name: Mengting
full_name: Lu, Mengting
id: a8198a14-1ffe-11ee-8b67-d2bdff9d9178
last_name: Lu
- first_name: M
full_name: Kwiatkowski, M
last_name: Kwiatkowski
- first_name: Yuanrong
full_name: Pei, Yuanrong
id: 98605edc-6ce7-11ee-95f3-cc16b866efcd
last_name: Pei
- first_name: K
full_name: Jaworski, K
last_name: Jaworski
- first_name: Jiří
full_name: Friml, Jiří
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
citation:
ama: Chen H, Qi L, Zou M, et al. TIR1-produced cAMP as a second messenger in transcriptional
auxin signalling. Nature. 2025;640:1011-1016. doi:10.1038/s41586-025-08669-w
apa: Chen, H., Qi, L., Zou, M., Lu, M., Kwiatkowski, M., Pei, Y., … Friml, J. (2025).
TIR1-produced cAMP as a second messenger in transcriptional auxin signalling.
Nature. Springer Nature. https://doi.org/10.1038/s41586-025-08669-w
chicago: Chen, Huihuang, Linlin Qi, Minxia Zou, Mengting Lu, M Kwiatkowski, Yuanrong
Pei, K Jaworski, and Jiří Friml. “TIR1-Produced CAMP as a Second Messenger in
Transcriptional Auxin Signalling.” Nature. Springer Nature, 2025. https://doi.org/10.1038/s41586-025-08669-w.
ieee: H. Chen et al., “TIR1-produced cAMP as a second messenger in transcriptional
auxin signalling,” Nature, vol. 640. Springer Nature, pp. 1011–1016, 2025.
ista: Chen H, Qi L, Zou M, Lu M, Kwiatkowski M, Pei Y, Jaworski K, Friml J. 2025.
TIR1-produced cAMP as a second messenger in transcriptional auxin signalling.
Nature. 640, 1011–1016.
mla: Chen, Huihuang, et al. “TIR1-Produced CAMP as a Second Messenger in Transcriptional
Auxin Signalling.” Nature, vol. 640, Springer Nature, 2025, pp. 1011–16,
doi:10.1038/s41586-025-08669-w.
short: H. Chen, L. Qi, M. Zou, M. Lu, M. Kwiatkowski, Y. Pei, K. Jaworski, J. Friml,
Nature 640 (2025) 1011–1016.
corr_author: '1'
date_created: 2025-03-19T09:44:39Z
date_published: 2025-04-24T00:00:00Z
date_updated: 2026-04-28T13:42:45Z
day: '24'
ddc:
- '580'
department:
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doi: 10.1038/s41586-025-08669-w
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grant_number: P37051
name: Guanylate cyclase activity of TIR1/AFBs auxin receptors
publication: Nature
publication_identifier:
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- 1476-4687
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- 0028-0836
publication_status: published
publisher: Springer Nature
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related_material:
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relation: press_release
url: https://ista.ac.at/en/news/updating-the-textbook/
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status: public
title: TIR1-produced cAMP as a second messenger in transcriptional auxin signalling
tmp:
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name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
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volume: 640
year: '2025'
...
---
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_id: '19478'
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: "This project was funded by the European Research Council Advanced
Grant (ETAP-742985),\r\nEuropean Research Council (ERC; 101142681 CYNIPS), Austrian
Science Fund (FWF; P\r\n37051-B)."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Huihuang
full_name: Chen, Huihuang
id: 83c96512-15b2-11ec-abd3-b7eede36184f
last_name: Chen
citation:
ama: Chen H. The cAMP second messenger in auxin signalling. 2025. doi:10.15479/AT-ISTA-19478
apa: Chen, H. (2025). The cAMP second messenger in auxin signalling. Institute
of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-19478
chicago: Chen, Huihuang. “The CAMP Second Messenger in Auxin Signalling.” Institute
of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-19478.
ieee: H. Chen, “The cAMP second messenger in auxin signalling,” Institute of Science
and Technology Austria, 2025.
ista: Chen H. 2025. The cAMP second messenger in auxin signalling. Institute of
Science and Technology Austria.
mla: Chen, Huihuang. The CAMP Second Messenger in Auxin Signalling. Institute
of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-19478.
short: H. Chen, The CAMP Second Messenger in Auxin Signalling, Institute of Science
and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-04-04T07:48:24Z
date_published: 2025-04-04T00:00:00Z
date_updated: 2026-04-28T13:42:45Z
day: '04'
ddc:
- '580'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JiFr
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ec_funded: 1
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language:
- iso: eng
month: '04'
oa_version: Published Version
page: '118'
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742985'
name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 7bcece63-9f16-11ee-852c-ae94e099eeb6
grant_number: P37051
name: Guanylate cyclase activity of TIR1/AFBs auxin receptors
- _id: 8f347782-16d5-11f0-9cad-8c19706ee739
grant_number: '101142681'
name: Cyclic nucleotides as second messengers in plants
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '13212'
relation: part_of_dissertation
status: public
- id: '19421'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Jiří
full_name: Friml, Jiří
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
title: The cAMP second messenger in auxin signalling
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
APC_amount: 3948 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '19593'
abstract:
- lang: eng
text: Prenatal immune challenges pose significant risks to human embryonic brain
and eye development. However, our knowledge about the safe usage of anti-inflammatory
drugs during pregnancy is still limited. While human induced pluripotent stem
cells (hIPSC)-derived brain organoid models have started to explore functional
consequences upon viral stimulation, these models commonly lack microglia, which
are susceptible to and promote inflammation. Furthermore, microglia are actively
involved in neuronal development. Here, we generate hIPSC-derived microglia precursor
cells and assemble them into retinal organoids. Once the outer plexiform layer
forms, these hIPSC-derived microglia (iMG) fully integrate into the retinal organoids.
Since the ganglion cell survival declines by this time in 3D-retinal organoids,
we adapted the model into 2D and identify that the improved ganglion cell number
significantly decreases only with iMG presence. In parallel, we applied the immunostimulant
POLY(I:C) to mimic a fetal viral infection. While POLY(I:C) exposure alters the
iMG phenotype, it does not hinder their interaction with ganglion cells. Furthermore,
iMG significantly enhance the supernatant’s inflammatory secretome and increase
retinal cell proliferation. Simultaneous exposure with the non-steroidal anti-inflammatory
drug (NSAID) ibuprofen dampens POLY(I:C)-mediated changes of the iMG phenotype
and ameliorates cell proliferation. Remarkably, while POLY(I:C) disrupts neuronal
calcium dynamics independent of iMG, ibuprofen rescues this effect only if iMG
are present. Mechanistically, ibuprofen targets the enzymes cyclooxygenase 1 and
2 (COX1/PTGS1 and COX2/PTGS2) simultaneously, from which iMG mainly express COX1.
Selective COX1 blockage fails to restore the calcium peak amplitude upon POLY(I:C)
stimulation, suggesting ibuprofen’s beneficial effect depends on the presence
and interplay of COX1 and COX2. These findings underscore the importance of microglia
in the context of prenatal immune challenges and provide insight into the mechanisms
by which ibuprofen exerts its protective effects during embryonic development.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
acknowledgement: We thank the scientific service units at ISTA, specifically the Lab
Support Facility (LSF), the Molecular Biology Services/Virus Services Team, specifically
Flavia Gama Gomes Leite and Mark Andrew Smyth, for the virus production, and the
Imaging and Optics Facility (IOF). We thank all members of the Siegert group and
Marco Benevento for their constant feedback on the project and comments on the manuscript.
A special thanks to Rouven Schulz for input on statistical analysis and sharing
R-scripts, Gloria Colombo for the introduction to cell sorting, Negar Vehdani and
Florianne Schoot Uiterkamp for their support in cell culture. This research was
supported by the Gesellschaft für Forschungsförderung Niederösterreich (grant No.
Sc19-017 to V.H.).
article_number: '98'
article_processing_charge: Yes
article_type: original
author:
- first_name: Verena
full_name: Hübschmann, Verena
id: 32B7C918-F248-11E8-B48F-1D18A9856A87
last_name: Hübschmann
- first_name: Medina
full_name: Korkut, Medina
id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
last_name: Korkut
orcid: 0000-0003-4309-2251
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Juan Pablo
full_name: Maya-Arteaga, Juan Pablo
id: c815d433-1f5d-11f0-a875-dad18b1e5924
last_name: Maya-Arteaga
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Schmied V, Korkut M, Venturino A, Maya-Arteaga JP, Siegert S. Microglia determine
an immune-challenged environment and facilitate ibuprofen action in human retinal
organoids. Journal of Neuroinflammation. 2025;22(1). doi:10.1186/s12974-025-03366-x
apa: Schmied, V., Korkut, M., Venturino, A., Maya-Arteaga, J. P., & Siegert,
S. (2025). Microglia determine an immune-challenged environment and facilitate
ibuprofen action in human retinal organoids. Journal of Neuroinflammation.
Springer Nature. https://doi.org/10.1186/s12974-025-03366-x
chicago: Schmied, Verena, Medina Korkut, Alessandro Venturino, Juan Pablo Maya-Arteaga,
and Sandra Siegert. “Microglia Determine an Immune-Challenged Environment and
Facilitate Ibuprofen Action in Human Retinal Organoids.” Journal of Neuroinflammation.
Springer Nature, 2025. https://doi.org/10.1186/s12974-025-03366-x.
ieee: V. Schmied, M. Korkut, A. Venturino, J. P. Maya-Arteaga, and S. Siegert, “Microglia
determine an immune-challenged environment and facilitate ibuprofen action in
human retinal organoids,” Journal of Neuroinflammation, vol. 22, no. 1.
Springer Nature, 2025.
ista: Schmied V, Korkut M, Venturino A, Maya-Arteaga JP, Siegert S. 2025. Microglia
determine an immune-challenged environment and facilitate ibuprofen action in
human retinal organoids. Journal of Neuroinflammation. 22(1), 98.
mla: Schmied, Verena, et al. “Microglia Determine an Immune-Challenged Environment
and Facilitate Ibuprofen Action in Human Retinal Organoids.” Journal of Neuroinflammation,
vol. 22, no. 1, 98, Springer Nature, 2025, doi:10.1186/s12974-025-03366-x.
short: V. Schmied, M. Korkut, A. Venturino, J.P. Maya-Arteaga, S. Siegert, Journal
of Neuroinflammation 22 (2025).
corr_author: '1'
date_created: 2025-04-20T22:01:28Z
date_published: 2025-04-03T00:00:00Z
date_updated: 2026-05-06T12:49:37Z
day: '03'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1186/s12974-025-03366-x
external_id:
isi:
- '001459311800002'
pmid:
- '40181459'
file:
- access_level: open_access
checksum: dcc355c21ab713e45fda5c61b5fa5299
content_type: application/pdf
creator: dernst
date_created: 2025-04-22T09:46:27Z
date_updated: 2025-04-22T09:46:27Z
file_id: '19607'
file_name: 2025_JourNeuroinflammation_Schmied.pdf
file_size: 4482167
relation: main_file
success: 1
file_date_updated: 2025-04-22T09:46:27Z
has_accepted_license: '1'
intvolume: ' 22'
isi: 1
issue: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 9B99D380-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-017
name: How human microglia shape developing neurons during health and inflammation
- _id: B67AFEDC-15C9-11EA-A837-991A96BB2854
name: IST Austria Open Access Fund
publication: Journal of Neuroinflammation
publication_identifier:
eissn:
- 1742-2094
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/pink-skies/
record:
- id: '20074'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Microglia determine an immune-challenged environment and facilitate ibuprofen
action in human retinal organoids
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 22
year: '2025'
...
---
APC_amount: 2236,02 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '19566'
abstract:
- lang: eng
text: "Purpose: Optic nerve crush (ONC) is a model for studying optic nerve trauma.
Unilateral ONC induces massive retinal ganglion cell (RGC) degeneration in the
affected eye, leading to vision loss within a month. A common assumption has been
that the non-injured contralateral eye is unaffected due to the minimal retino-retinal
projections of the RGCs at the chiasm. Yet, recently, microglia, the brain-resident
macrophages, have shown a responsive phenotype in the contralateral eye after
ONC. Whether RGC loss accompanies this phenotype is still controversial.\r\n\r\nMethods:
Using the available RGCode algorithm and developing our own RGC-Quant deep-learning-based
tool, we quantify RGC's total number and density across the entire retina after
ONC.\r\n\r\nResults: We confirm a short-term microglia response in the contralateral
eye after ONC, but this did not affect the microglia number. Furthermore, we cannot
confirm the previously reported RGC loss between naïve and contralateral retinas
5 weeks after ONC induction across the commonly used Cx3cr1creERT2 and C57BL6/J
mouse models. Neither sex nor the direct comparison of the RGC markers Brn3a and
RBPMS, with Brn3a co-labeling, on average, 89% of the RBPMS+-cells, explained
this discrepancy, suggesting that the early microglia-responsive phenotype does
not have immediate consequences on the RGC number.\r\n\r\nConclusions: Our results
corroborate that unilateral optic nerve injury elicits a microglial response in
the uninjured contralateral eye but without RGC loss. Therefore, the contralateral
eye should be treated separately and not as an ONC control."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: "The authors thank the Scientific Service Units (SSU) of ISTA for
the provided resources, specifically the Imaging and Optics Facility (IOF), the
Lab Support Facility (LSF), and the Pre-Clinical Facility (PCF) team, specifically
Sonja Haslinger, Claudia Gold, and Michael Schunn, for mouse colony management and
support. We thank all members of the Siegert group for constant feedback on the
project and the manuscript. \r\nSupported in whole or in part by the Austrian Science
Fund (FWF) [10.55776/P37131]. For open access purposes, the author has applied a
CC BY public copyright license to any author-accepted manuscript version arising
from this submission. "
article_number: '49'
article_processing_charge: Yes
article_type: original
author:
- first_name: Florianne E
full_name: Schoot Uiterkamp, Florianne E
id: 3526230C-F248-11E8-B48F-1D18A9856A87
last_name: Schoot Uiterkamp
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Mohammad
full_name: Alamalhoda, Mohammad
last_name: Alamalhoda
- first_name: Arsalan
full_name: Firoozi, Arsalan
last_name: Firoozi
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Miteva FE, Maes ME, Alamalhoda M, Firoozi A, Colombo G, Siegert S. Optic nerve
crush does not induce retinal ganglion cell loss in the contralateral eye. Investigative
Ophthalmology & Visual Science. 2025;66(3). doi:10.1167/iovs.66.3.49
apa: Miteva, F. E., Maes, M. E., Alamalhoda, M., Firoozi, A., Colombo, G., &
Siegert, S. (2025). Optic nerve crush does not induce retinal ganglion cell loss
in the contralateral eye. Investigative Ophthalmology & Visual Science.
Association for Research in Vision and Ophthalmology. https://doi.org/10.1167/iovs.66.3.49
chicago: Miteva, Florianne E, Margaret E Maes, Mohammad Alamalhoda, Arsalan Firoozi,
Gloria Colombo, and Sandra Siegert. “Optic Nerve Crush Does Not Induce Retinal
Ganglion Cell Loss in the Contralateral Eye.” Investigative Ophthalmology &
Visual Science. Association for Research in Vision and Ophthalmology, 2025.
https://doi.org/10.1167/iovs.66.3.49.
ieee: F. E. Miteva, M. E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, and S. Siegert,
“Optic nerve crush does not induce retinal ganglion cell loss in the contralateral
eye,” Investigative Ophthalmology & Visual Science, vol. 66, no. 3.
Association for Research in Vision and Ophthalmology, 2025.
ista: Miteva FE, Maes ME, Alamalhoda M, Firoozi A, Colombo G, Siegert S. 2025. Optic
nerve crush does not induce retinal ganglion cell loss in the contralateral eye.
Investigative Ophthalmology & Visual Science. 66(3), 49.
mla: Miteva, Florianne E., et al. “Optic Nerve Crush Does Not Induce Retinal Ganglion
Cell Loss in the Contralateral Eye.” Investigative Ophthalmology & Visual
Science, vol. 66, no. 3, 49, Association for Research in Vision and Ophthalmology,
2025, doi:10.1167/iovs.66.3.49.
short: F.E. Miteva, M.E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, S. Siegert,
Investigative Ophthalmology & Visual Science 66 (2025).
corr_author: '1'
date_created: 2025-04-15T13:40:35Z
date_published: 2025-03-01T00:00:00Z
date_updated: 2026-05-20T06:37:12Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1167/iovs.66.3.49
external_id:
pmid:
- '40126507'
file:
- access_level: open_access
checksum: e8722ce5792f6c08fe1e191f7de6f147
content_type: application/pdf
creator: dernst
date_created: 2025-04-15T13:49:10Z
date_updated: 2025-04-15T13:49:10Z
file_id: '19567'
file_name: 2025_IOVS_SchootUiterkamp.pdf
file_size: 2721477
relation: main_file
success: 1
file_date_updated: 2025-04-15T13:49:10Z
has_accepted_license: '1'
intvolume: ' 66'
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 7be82147-9f16-11ee-852c-f44682d73140
grant_number: P37131
name: Dissecting the morpho-functional relationship of microglia
- _id: 3AC91DDA-15DF-11EA-824D-93A3E7B544D1
call_identifier: FWF
name: FWF Open Access Fund
publication: Investigative Ophthalmology & Visual Science
publication_identifier:
issn:
- 1552-5783
publication_status: published
publisher: Association for Research in Vision and Ophthalmology
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/siegert-lab/RGC-Quant
record:
- id: '20467'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Optic nerve crush does not induce retinal ganglion cell loss in the contralateral
eye
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 66
year: '2025'
...
---
OA_place: publisher
_id: '20467'
acknowledged_ssus:
- _id: Bio
- _id: SSU
- _id: PreCl
- _id: LifeSc
acknowledgement: "The work presented in this Thesis was carried out at the Institute
of Science and Technology\r\nAustria (ISTA), and was supported by the Austrian Science
Fund (FWF) [10.55776/P37131].\r\nI would like to thank the Scientific Service Units
(SSU) of ISTA for the provided resources,\r\nspecifically the Imaging and Optics
Facility (IOF), the Lab Support Facility (LSF), and the\r\nPre-Clinical Facility
(PCF) team, specifically Sonja Haslinger, Claudia Gold, and Michael\r\nSchunn, for
mouse colony management and support. "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Florianne E
full_name: Miteva, Florianne E
id: 3526230C-F248-11E8-B48F-1D18A9856A87
last_name: Miteva
citation:
ama: Miteva FE. The role of cyclooxygenase 1 on microglial response to inflammatory
stressors. 2025. doi:10.15479/AT-ISTA-20467
apa: Miteva, F. E. (2025). The role of cyclooxygenase 1 on microglial response
to inflammatory stressors. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20467
chicago: Miteva, Florianne E. “The Role of Cyclooxygenase 1 on Microglial Response
to Inflammatory Stressors.” Institute of Science and Technology Austria, 2025.
https://doi.org/10.15479/AT-ISTA-20467.
ieee: F. E. Miteva, “The role of cyclooxygenase 1 on microglial response to inflammatory
stressors,” Institute of Science and Technology Austria, 2025.
ista: Miteva FE. 2025. The role of cyclooxygenase 1 on microglial response to inflammatory
stressors. Institute of Science and Technology Austria.
mla: Miteva, Florianne E. The Role of Cyclooxygenase 1 on Microglial Response
to Inflammatory Stressors. Institute of Science and Technology Austria, 2025,
doi:10.15479/AT-ISTA-20467.
short: F.E. Miteva, The Role of Cyclooxygenase 1 on Microglial Response to Inflammatory
Stressors, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-10-14T10:24:41Z
date_published: 2025-10-14T00:00:00Z
date_updated: 2026-05-20T06:37:12Z
day: '14'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SaSi
doi: 10.15479/AT-ISTA-20467
file:
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checksum: 03537697be8c688d3a05cf948288e48f
content_type: application/pdf
creator: fschootu
date_created: 2025-10-17T11:09:11Z
date_updated: 2025-10-17T11:13:25Z
embargo: 2026-10-14
embargo_to: open_access
file_id: '20484'
file_name: 2025_Miteva_Florianne_thesis.pdf
file_size: 13668588
relation: main_file
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creator: fschootu
date_created: 2025-10-23T11:33:06Z
date_updated: 2025-10-23T11:33:06Z
file_id: '20525'
file_name: 2025_Miteva_florianne_thesis.docx
file_size: 28991918
relation: source_file
file_date_updated: 2025-10-23T11:33:06Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa_version: Published Version
page: '99'
project:
- _id: 7be82147-9f16-11ee-852c-f44682d73140
grant_number: P37131
name: Dissecting the morpho-functional relationship of microglia
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '19566'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
title: The role of cyclooxygenase 1 on microglial response to inflammatory stressors
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
APC_amount: 3642,79 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '20080'
abstract:
- lang: eng
text: "Introduction: Acid-growth theory has been postulated in the 70s to explain
the rapid elongation of plant cells in response to the hormone auxin. More recently,
it has been demonstrated that activation of the proton ATPs pump (H+-ATPs) promoting
acidification of the apoplast is the principal mechanism by which auxin and other
hormones such as brassinosteroids (BR) induce cell elongation. Despite these advances,
the impact of this acidification on the mechanical properties of the cell wall
remained largely unexplored.\r\n\r\nMethods: Here, we use elongation assays of
Arabidopsis thaliana hypocotyls and Atomic Force Microscopy (AFM) to correlate
hormone-induced tissue elongation and local changes in cell wall mechanical properties.
Furthermore, employing transgenic lines over-expressing Pectin Methyl Esterase
(PME), along with calcium chelators, we investigate the effect of pectin modification
in hormone-driven cell elongation.\r\n\r\nResults: We demonstrate that acidification
of apoplast is necessary and sufficient to induce cell elongation through promoting
cell wall softening. Moreover, we show that enhanced PME activity can induce both
cell wall softening or stiffening in extracellular calcium dependent-manner and
that tight control of PME activity is required for proper hypocotyl elongation.\r\n\r\nDiscussion:
Our results confirm a dual role of PME in plant cell elongation. However, further
investigation is needed to assess the status of pectin following short- or long-term
PME treatments in order to determine if pectin methyl-esterification might promote
its degradation as well as the role of PME inhibitors upon PME induction."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: E-Lib
acknowledgement: "The author(s) declare that financial support was received for the
research and/or publication of this article. This work was supported by grants from
the European Research Council (Starting Independent Research Grant ERC-2007-Stg-
207362-HCPO to EB) and MG was recipient of an IST Interdisciplinary project (IC1022IPC03).\r\nWe
acknowledge Jaume F. Martı́nez Garcı́a for phyAphyB mutant seeds. We acknowledge
CF Nanobiotechnology of CIISB, Instruct-CZ Centre, supported by MEYS CR (LM2018127).
We gratefully acknowledge support by the Scientific Service Units at ISTA, including
the Imaging and Optics and Lab Support facilities and Library. We thank Stefan Riegler
for the efforts to establish immunodetection method."
article_number: '1612366'
article_processing_charge: Yes
article_type: original
author:
- first_name: Marçal
full_name: Gallemi, Marçal
id: 460C6802-F248-11E8-B48F-1D18A9856A87
last_name: Gallemi
orcid: 0000-0003-4675-6893
- first_name: Juan C
full_name: Montesinos López, Juan C
id: 310A8E3E-F248-11E8-B48F-1D18A9856A87
last_name: Montesinos López
orcid: 0000-0001-9179-6099
- first_name: Nikola
full_name: Zarevski, Nikola
id: 18e95355-e05a-11ea-a9c0-8fba1b89e83a
last_name: Zarevski
- first_name: Jan
full_name: Pribyl, Jan
last_name: Pribyl
- first_name: Petr
full_name: Skládal, Petr
last_name: Skládal
- 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: Eva
full_name: Benková, Eva
id: 38F4F166-F248-11E8-B48F-1D18A9856A87
last_name: Benková
orcid: 0000-0002-8510-9739
citation:
ama: Gallemi M, Montesinos López JC, Zarevski N, et al. Dual role of pectin methyl
esterase activity in the regulation of plant cell wall biophysical properties.
Frontiers in Plant Science. 2025;16. doi:10.3389/fpls.2025.1612366
apa: Gallemi, M., Montesinos López, J. C., Zarevski, N., Pribyl, J., Skládal, P.,
Hannezo, E. B., & Benková, E. (2025). Dual role of pectin methyl esterase
activity in the regulation of plant cell wall biophysical properties. Frontiers
in Plant Science. Frontiers Media. https://doi.org/10.3389/fpls.2025.1612366
chicago: Gallemi, Marçal, Juan C Montesinos López, Nikola Zarevski, Jan Pribyl,
Petr Skládal, Edouard B Hannezo, and Eva Benková. “Dual Role of Pectin Methyl
Esterase Activity in the Regulation of Plant Cell Wall Biophysical Properties.”
Frontiers in Plant Science. Frontiers Media, 2025. https://doi.org/10.3389/fpls.2025.1612366.
ieee: M. Gallemi et al., “Dual role of pectin methyl esterase activity in
the regulation of plant cell wall biophysical properties,” Frontiers in Plant
Science, vol. 16. Frontiers Media, 2025.
ista: Gallemi M, Montesinos López JC, Zarevski N, Pribyl J, Skládal P, Hannezo EB,
Benková E. 2025. Dual role of pectin methyl esterase activity in the regulation
of plant cell wall biophysical properties. Frontiers in Plant Science. 16, 1612366.
mla: Gallemi, Marçal, et al. “Dual Role of Pectin Methyl Esterase Activity in the
Regulation of Plant Cell Wall Biophysical Properties.” Frontiers in Plant Science,
vol. 16, 1612366, Frontiers Media, 2025, doi:10.3389/fpls.2025.1612366.
short: M. Gallemi, J.C. Montesinos López, N. Zarevski, J. Pribyl, P. Skládal, E.B.
Hannezo, E. Benková, Frontiers in Plant Science 16 (2025).
corr_author: '1'
date_created: 2025-07-27T22:01:26Z
date_published: 2025-07-04T00:00:00Z
date_updated: 2026-05-20T07:53:03Z
day: '04'
ddc:
- '580'
department:
- _id: EdHa
- _id: EvBe
- _id: CaGu
doi: 10.3389/fpls.2025.1612366
ec_funded: 1
external_id:
isi:
- '001530690900001'
pmid:
- '40688689'
file:
- access_level: open_access
checksum: 9e6b8b53ba56d4a24a9bd91cf6d2dc58
content_type: application/pdf
creator: dernst
date_created: 2025-07-31T07:28:54Z
date_updated: 2025-07-31T07:28:54Z
file_id: '20093'
file_name: 2025_FrontiersPlantSc_Gallemi.pdf
file_size: 3665187
relation: main_file
success: 1
file_date_updated: 2025-07-31T07:28:54Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 253FCA6A-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '207362'
name: Hormonal cross-talk in plant organogenesis
- _id: B67AFEDC-15C9-11EA-A837-991A96BB2854
name: IST Austria Open Access Fund
publication: Frontiers in Plant Science
publication_identifier:
eissn:
- 1664-462X
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dual role of pectin methyl esterase activity in the regulation of plant cell
wall biophysical properties
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2025'
...
---
APC_amount: 7068 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '20929'
abstract:
- lang: eng
text: Insulin/insulin-like growth factor signaling inhibits FOXO transcription factors
to control development, homeostasis, and aging. Here, we use proximity labeling
to identify proteins interacting with the C. elegans FOXO DAF-16. We show that
in well-fed, unstressed animals harboring active insulin signaling, DAF-16 forms
a complex with the PAR-1/MARK serine/threonine kinase, a key regulator of cell
polarity. PAR-1 inhibits DAF-16 accumulation and promotes DAF-16 phosphorylation
at S249, at a conserved motif that PAR-1/human MARK2 phosphorylates in vitro.
DAF-2 insulin-like receptor signaling stimulates DAF-16 S249 phosphorylation,
suggesting DAF-2 activates PAR-1. DAF-2 also promotes PAR-1 expression by inhibiting
DAF-16. PAR-1 knockdown, or DAF-16 S249A, prolong lifespan, whereas phosphomimetic
DAF-16 S249D suppresses the longevity of daf-2 mutants. At low insulin signaling,
DAF-16 proximity labeling highlights transcription factors, chromatin regulators,
and DNA repair proteins. One interactor, the zinc finger/homeobox protein ZFH-2/ZFHX3,
forms a complex with DAF-16 and prolongs lifespan. Our work provides entry points
for hypothesis-driven studies of FOXO function and longevity.
acknowledged_ssus:
- _id: Bio
acknowledgement: We thank de Bono lab members for helpful comments on the manuscript,
and the Mass Spec Facility at the Max Perutz Labs, notably WeiQiang Chen and Markus
Hartl, for invaluable discussions and comments on mass spec analyses of worm samples.
All LC-MS/MS analyses were performed on instruments of the Vienna BioCenter Core
Facilities (VBCF). Microscopy was supported by the Scientific Services Units (SSU)
of ISTA through resources provided by the Imaging & Optics Facility (IOF). We are
grateful to Dr. Geraldine Seydoux (Johns Hopkins University) for worm strains and
plasmids, and Dr. Seung-Jae V. Lee (KAIST) for RNAi clones. We are grateful to Ekaterina
Lashmanova for designing the daf-16::TbID::mNG::3xFLAG knock-in construct and for
her outstanding support in the lab. This work was supported by a Wellcome Investigator
Award (209504/A/17/Z) to MdB and an ISTplus Fellowship to MA (Marie Sklodowska-Curie
agreement No 754411).
article_number: '11355'
article_processing_charge: Yes
article_type: original
author:
- first_name: Murat
full_name: Artan, Murat
id: C407B586-6052-11E9-B3AE-7006E6697425
last_name: Artan
orcid: 0000-0001-8945-6992
- first_name: Hanna
full_name: Schön, Hanna
id: C8E17EDC-D7AA-11E9-B7B7-45ECE5697425
last_name: Schön
- first_name: Mario
full_name: De Bono, Mario
id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
last_name: De Bono
orcid: 0000-0001-8347-0443
citation:
ama: Artan M, Schön H, de Bono M. Proximity labeling of DAF-16 FOXO highlights aging
regulatory proteins. Nature Communications. 2025;16. doi:10.1038/s41467-025-66409-0
apa: Artan, M., Schön, H., & de Bono, M. (2025). Proximity labeling of DAF-16
FOXO highlights aging regulatory proteins. Nature Communications. Springer
Nature. https://doi.org/10.1038/s41467-025-66409-0
chicago: Artan, Murat, Hanna Schön, and Mario de Bono. “Proximity Labeling of DAF-16
FOXO Highlights Aging Regulatory Proteins.” Nature Communications. Springer
Nature, 2025. https://doi.org/10.1038/s41467-025-66409-0.
ieee: M. Artan, H. Schön, and M. de Bono, “Proximity labeling of DAF-16 FOXO highlights
aging regulatory proteins,” Nature Communications, vol. 16. Springer Nature,
2025.
ista: Artan M, Schön H, de Bono M. 2025. Proximity labeling of DAF-16 FOXO highlights
aging regulatory proteins. Nature Communications. 16, 11355.
mla: Artan, Murat, et al. “Proximity Labeling of DAF-16 FOXO Highlights Aging Regulatory
Proteins.” Nature Communications, vol. 16, 11355, Springer Nature, 2025,
doi:10.1038/s41467-025-66409-0.
short: M. Artan, H. Schön, M. de Bono, Nature Communications 16 (2025).
corr_author: '1'
date_created: 2026-01-04T23:01:34Z
date_published: 2025-12-11T00:00:00Z
date_updated: 2026-05-20T08:10:18Z
day: '11'
ddc:
- '570'
department:
- _id: MaDe
doi: 10.1038/s41467-025-66409-0
ec_funded: 1
external_id:
pmid:
- '41381452'
file:
- access_level: open_access
checksum: 748e2e003b878b85b6048d51621d6aae
content_type: application/pdf
creator: dernst
date_created: 2026-01-05T10:58:28Z
date_updated: 2026-01-05T10:58:28Z
file_id: '20941'
file_name: 2025_NatureComm_Artan.pdf
file_size: 1642352
relation: main_file
success: 1
file_date_updated: 2026-01-05T10:58:28Z
has_accepted_license: '1'
intvolume: ' 16'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 23870BE8-32DE-11EA-91FC-C7463DDC885E
grant_number: 209504/A/17/Z
name: Molecular mechanisms of neural circuit function
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2025'
...
---
APC_amount: 5949 EUR
OA_place: publisher
OA_type: hybrid
_id: '19626'
abstract:
- lang: eng
text: Active regulation of gene expression, orchestrated by complex interactions
of activators and repressors at promoters, controls the fate of organisms. In
contrast, basal expression at uninduced promoters is considered to be a dynamically
inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional
regulation. Here, we investigate the basal expression mode of the mar operon,
the main regulator of intrinsic multiple antibiotic resistance in Escherichia
coli, and link its dynamic properties to the noncanonical, yet highly conserved
start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements
across tens of generations reveal that basal expression consists of rare stochastic
gene expression pulses, which maximize variability in wildtype and, surprisingly,
transiently accelerate cellular elongation rates. Competition experiments show
that basal expression confers fitness advantages to wildtype across several transitions
between exponential and stationary growth by shortening lag times. The dynamically
rich basal expression of the mar operon has likely been evolutionarily maintained
for its role in growth homeostasis of Enterobacteria within the gut environment,
thereby allowing other ancillary gene regulatory roles to evolve, e.g., control
of costly-to-induce multidrug efflux pumps. Understanding the complex selection
forces governing genetic systems involved in intrinsic multidrug resistance is
crucial for effective public health measures.
acknowledged_ssus:
- _id: Bio
acknowledgement: K.J. thanks B. Wu, I. Tomanek, K. Tomasek for detailed discussions
on the manuscript, all other members from the Guet laboratory for valuable feedback,
R. Chait, & Imaging and Optics Facility, Institute of Science and Technology Austria
for helping with microscopy, Dr. Sudha Rao and Dr. Raja Mugasimangalam, Genotypic
Technology India for allowing time off to address the revisions. K.J. acknowledges
Institute of Science and Technology fellowship IC1006FELL02, R.H. was supported
in part by Chan Zuckerberg Initiative and Donor Advised-Fund grant 2020-225401 (https://doi.org/10.37921/120055ratwvi),
O.O.B. acknowledges Fonds Zur Förderung der Wissenschaftlichen Forschung (FWF) Grant
ESP253-B, R.R. acknowledges FWF Grant 10.55776/ESP219, C.C.G. acknowledges FWF I5127-B.
article_number: e2413709122
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Kirti
full_name: Jain, Kirti
id: 330F0278-F248-11E8-B48F-1D18A9856A87
last_name: Jain
orcid: 0000-0002-3809-0449
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Olga
full_name: Bochkareva, Olga
id: C4558D3C-6102-11E9-A62E-F418E6697425
last_name: Bochkareva
orcid: 0000-0003-1006-6639
- first_name: Roderich
full_name: Römhild, Roderich
id: 68E56E44-62B0-11EA-B963-444F3DDC885E
last_name: Römhild
orcid: 0000-0001-9480-5261
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Pulsatile
basal gene expression as a fitness determinant in bacteria. Proceedings of
the National Academy of Sciences. 2025;122(15). doi:10.1073/pnas.2413709122
apa: Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., & Guet,
C. C. (2025). Pulsatile basal gene expression as a fitness determinant in bacteria.
Proceedings of the National Academy of Sciences. National Academy of Sciences.
https://doi.org/10.1073/pnas.2413709122
chicago: Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper
Tkačik, and Calin C Guet. “Pulsatile Basal Gene Expression as a Fitness Determinant
in Bacteria.” Proceedings of the National Academy of Sciences. National
Academy of Sciences, 2025. https://doi.org/10.1073/pnas.2413709122.
ieee: K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet,
“Pulsatile basal gene expression as a fitness determinant in bacteria,” Proceedings
of the National Academy of Sciences, vol. 122, no. 15. National Academy of
Sciences, 2025.
ista: Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Pulsatile
basal gene expression as a fitness determinant in bacteria. Proceedings of the
National Academy of Sciences. 122(15), e2413709122.
mla: Jain, Kirti, et al. “Pulsatile Basal Gene Expression as a Fitness Determinant
in Bacteria.” Proceedings of the National Academy of Sciences, vol. 122,
no. 15, e2413709122, National Academy of Sciences, 2025, doi:10.1073/pnas.2413709122.
short: K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings
of the National Academy of Sciences 122 (2025).
corr_author: '1'
date_created: 2025-04-27T22:02:13Z
date_published: 2025-04-15T00:00:00Z
date_updated: 2026-05-20T08:33:08Z
day: '15'
ddc:
- '570'
department:
- _id: CaGu
- _id: Bio
- _id: FyKo
- _id: GaTk
doi: 10.1073/pnas.2413709122
external_id:
isi:
- '001471235200001'
pmid:
- '40193613'
file:
- access_level: open_access
checksum: 115a687f40009660eb4b38b4f6559d41
content_type: application/pdf
creator: dernst
date_created: 2025-06-24T07:27:43Z
date_updated: 2025-06-24T07:27:43Z
file_id: '19888'
file_name: 2025_PNAS_Jain.pdf
file_size: 2949523
relation: main_file
success: 1
file_date_updated: 2025-06-24T07:27:43Z
has_accepted_license: '1'
intvolume: ' 122'
isi: 1
issue: '15'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473
grant_number: CZI01
name: Tools for automation and feedback microscopy
- _id: bd6f94d1-d553-11ed-ba76-ae9f07250f74
grant_number: E219
name: Non-canonical antibiotic interactions
- _id: 34e076d6-11ca-11ed-8bc3-aec76c41a181
grant_number: I05127
name: Evolutionary analysis of gene regulation
publication: Proceedings of the National Academy of Sciences
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/
record:
- id: '19294'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Pulsatile basal gene expression as a fitness determinant in bacteria
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 122
year: '2025'
...
---
APC_amount: 4215,38 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '19963'
abstract:
- lang: eng
text: The acquisition of cellular identity requires large-scale alterations in cellular
state. The noncanonical proteasome activator PSME3 is known to regulate diverse
cellular processes, but its importance for differentiation remains unclear. Here,
we demonstrate that PSME3 binds dynamically to highly active promoters over the
course of differentiation. However, loss of PSME3 does not globally affect mRNA
transcription. We find instead that PSME3 influences the levels of several adhesion-related
proteins and acts upstream of the HSP90 co-chaperone NUDC to regulate cell motility
and myoblast differentiation in a proteasome-independent manner. Our findings
reveal several new facets of PSME3 functionality and highlight its importance
for the differentiation of myogenic cells.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
acknowledgement: 'All proteomics analysis was done by the ISTA LSF Mass Spectrometry
Service: Ewelina Dutkiewicz-Kopczynska processed the samples (digest and cleanup);
Bella Bruszel optimized the acquisition methods, acquired the data, and performed
all searches; and Armel Nicolas provided pre- and post-project consulting and post-processed
the search results using a development version of their data analysis package, proteoCraft
(publication pending). The authors would like to thank Saki for their clarity of
thought and insight, as well as Dr. Lorenzo Puri and the members of his laboratory
for invaluable discussions relating to the project. This research was further supported
by the Lab Support Facility and the Imaging and Optics Facility of ISTA.'
article_number: e202503208
article_processing_charge: Yes
article_type: original
author:
- first_name: Kenneth D
full_name: Kuhn, Kenneth D
id: 7deed7e0-0133-11f0-8590-c4600b08d0f4
last_name: Kuhn
- first_name: Ukrae H.
full_name: Cho, Ukrae H.
last_name: Cho
- first_name: Martin W
full_name: Hetzer, Martin W
id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
last_name: Hetzer
orcid: 0000-0002-2111-992X
citation:
ama: Kuhn KD, Cho UH, Hetzer M. PSME3 regulates migration and differentiation of
myoblasts. Life Science Alliance. 2025;8(9). doi:10.26508/lsa.202503208
apa: Kuhn, K. D., Cho, U. H., & Hetzer, M. (2025). PSME3 regulates migration
and differentiation of myoblasts. Life Science Alliance. Embo Press. https://doi.org/10.26508/lsa.202503208
chicago: Kuhn, Kenneth D, Ukrae H. Cho, and Martin Hetzer. “PSME3 Regulates Migration
and Differentiation of Myoblasts.” Life Science Alliance. Embo Press, 2025.
https://doi.org/10.26508/lsa.202503208.
ieee: K. D. Kuhn, U. H. Cho, and M. Hetzer, “PSME3 regulates migration and differentiation
of myoblasts,” Life Science Alliance, vol. 8, no. 9. Embo Press, 2025.
ista: Kuhn KD, Cho UH, Hetzer M. 2025. PSME3 regulates migration and differentiation
of myoblasts. Life Science Alliance. 8(9), e202503208.
mla: Kuhn, Kenneth D., et al. “PSME3 Regulates Migration and Differentiation of
Myoblasts.” Life Science Alliance, vol. 8, no. 9, e202503208, Embo Press,
2025, doi:10.26508/lsa.202503208.
short: K.D. Kuhn, U.H. Cho, M. Hetzer, Life Science Alliance 8 (2025).
corr_author: '1'
date_created: 2025-07-06T22:01:22Z
date_published: 2025-09-01T00:00:00Z
date_updated: 2026-05-20T08:38:04Z
day: '01'
ddc:
- '570'
department:
- _id: MaHe
doi: 10.26508/lsa.202503208
external_id:
isi:
- '001511452100001'
pmid:
- '40537284'
file:
- access_level: open_access
checksum: 591d47aa39fc969986c7d3b966890f5f
content_type: application/pdf
creator: dernst
date_created: 2025-12-30T09:17:09Z
date_updated: 2025-12-30T09:17:09Z
file_id: '20904'
file_name: 2025_LifeScienceAlliance_Kuhn.pdf
file_size: 5471288
relation: main_file
success: 1
file_date_updated: 2025-12-30T09:17:09Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: B67AFEDC-15C9-11EA-A837-991A96BB2854
name: IST Austria Open Access Fund
publication: Life Science Alliance
publication_identifier:
eissn:
- 2575-1077
publication_status: published
publisher: Embo Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: PSME3 regulates migration and differentiation of myoblasts
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 8
year: '2025'
...
---
APC_amount: 5766,07 EUR
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20289'
abstract:
- lang: eng
text: Cell and tissue movement in development, cancer invasion, and immune response
relies on chemical or mechanical guidance cues. In many systems, this behavior
is locally directed by self-generated signaling gradients rather than long-range,
prepatterned cues. However, how heterogeneous mixtures of cells interact nonreciprocally
and navigate through self-generated gradients remains largely unexplored. Here,
we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous
cell populations. We find that the relative chemotactic sensitivities of different
cell populations control their long-time coupling and comigration dynamics, with
boundary conditions such as external cell and attractant reservoirs substantially
influencing the migration patterns. Our model predicts an optimal parameter regime
that enables robust and colocalized migration. We test our theoretical predictions
with in vitro experiments demonstrating the comigration of distinct immune cell
populations, and quantitatively reproduce observed migration patterns under wild-type
and perturbed conditions. Interestingly, immune cell comigration occurs close
to the predicted optimal regime. Finally, we incorporate mechanical interactions
into our framework, revealing a nontrivial interplay between chemotactic and mechanical
nonreciprocity in driving collective migration. Together, our findings suggest
that self-generated chemotaxis is a robust strategy for the navigation of mixed
cell populations.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: NanoFab
acknowledgement: We thank all members of the M.S. and E.H. groups for stimulating
discussions.We thank the Imaging and Optics facility, the Pre-clinical and Lab Support
facility of the Institute of Science and Technology Austria for their excellent
support and provided resources for the experimental research. In particular, we
thank Jack Merrin from the Nanofabrication facility who generated the microfabricated
channel used in this study. This work received funding fromt he European Research
Council under the European Union’s Horizon 2020 research and innovation program
(grant agreement No. 851288 to E.H.). M.C.U.is funded by a University of Sheffield
Strategic Research Fellowship in the Physics of Life and Quantitative Biology.
article_number: e2504064122
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Mehmet C
full_name: Ucar, Mehmet C
id: 50B2A802-6007-11E9-A42B-EB23E6697425
last_name: Ucar
orcid: 0000-0003-0506-4217
- first_name: Alsberga
full_name: Zane, Alsberga
id: 60f7509a-f652-11ea-9d86-b963d6490d7c
last_name: Zane
orcid: 0009-0003-0415-7603
- 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: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
citation:
ama: Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. Self-generated chemotaxis
of mixed cell populations. Proceedings of the National Academy of Sciences.
2025;122(34). doi:10.1073/pnas.2504064122
apa: Ucar, M. C., Zane, A., Alanko, J. H., Sixt, M. K., & Hannezo, E. B. (2025).
Self-generated chemotaxis of mixed cell populations. Proceedings of the National
Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2504064122
chicago: Ucar, Mehmet C, Alsberga Zane, Jonna H Alanko, Michael K Sixt, and Edouard
B Hannezo. “Self-Generated Chemotaxis of Mixed Cell Populations.” Proceedings
of the National Academy of Sciences. National Academy of Sciences, 2025. https://doi.org/10.1073/pnas.2504064122.
ieee: M. C. Ucar, A. Zane, J. H. Alanko, M. K. Sixt, and E. B. Hannezo, “Self-generated
chemotaxis of mixed cell populations,” Proceedings of the National Academy
of Sciences, vol. 122, no. 34. National Academy of Sciences, 2025.
ista: Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. 2025. Self-generated chemotaxis
of mixed cell populations. Proceedings of the National Academy of Sciences. 122(34),
e2504064122.
mla: Ucar, Mehmet C., et al. “Self-Generated Chemotaxis of Mixed Cell Populations.”
Proceedings of the National Academy of Sciences, vol. 122, no. 34, e2504064122,
National Academy of Sciences, 2025, doi:10.1073/pnas.2504064122.
short: M.C. Ucar, A. Zane, J.H. Alanko, M.K. Sixt, E.B. Hannezo, Proceedings of
the National Academy of Sciences 122 (2025).
corr_author: '1'
date_created: 2025-09-07T22:01:32Z
date_published: 2025-08-26T00:00:00Z
date_updated: 2026-05-20T08:59:54Z
day: '26'
ddc:
- '570'
department:
- _id: EdHa
- _id: MiSi
doi: 10.1073/pnas.2504064122
ec_funded: 1
external_id:
isi:
- '001562181600001'
pmid:
- '40838890'
file:
- access_level: open_access
checksum: b36abd92673b6d76376fc9434bad52cc
content_type: application/pdf
creator: dernst
date_created: 2025-09-08T07:23:29Z
date_updated: 2025-09-08T07:23:29Z
file_id: '20307'
file_name: 2025_PNAS_Ucar.pdf
file_size: 16069140
relation: main_file
success: 1
file_date_updated: 2025-09-08T07:23:29Z
has_accepted_license: '1'
intvolume: ' 122'
isi: 1
issue: '34'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
publication: Proceedings of the National Academy of Sciences
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/mehmetcanucar/Self-generated-chemotaxis
scopus_import: '1'
status: public
title: Self-generated chemotaxis of mixed cell populations
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 122
year: '2025'
...
---
APC_amount: 7068 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '20424'
abstract:
- lang: eng
text: Homeostasis relies on a precise balance of fate choices between renewal and
differentiation. Although progress has been done to characterize the dynamics
of single-cell fate choices, their underlying mechanistic basis often remains
unclear. Concentrating on skin epidermis as a paradigm for multilayered tissues
with complex fate choices, we develop a 3D vertex-based model with proliferation
in the basal layer, showing that mechanical competition for space naturally gives
rise to homeostasis and neutral drift dynamics that are seen experimentally. We
then explore the effect of introducing mechanical heterogeneities between cellular
subpopulations. We uncover that relatively small tension heterogeneities, reflected
by distinct morphological changes in single-cell shapes, can be sufficient to
heavily tilt cellular dynamics towards exponential growth. We thus derive a master
relationship between cell shape and long-term clonal dynamics, which we validated
during basal cell carcinoma initiation in mouse epidermis. Altogether, we propose
a theoretical framework to link mechanical forces, quantitative cellular morphologies
and cellular fate outcomes in complex tissues.
acknowledged_ssus:
- _id: Bio
acknowledgement: We thank Alois Schlögl, Paula Sanematsu, Susana Moreno Flores, Bernat
Corominas-Murtra, Stefania Tavano, Gayathri Singharaju, and Hannezo group members
for helpful discussions, the Bioimaging facility at ISTA, as well as Matthias Merkel
and Lisa Manning for sharing the 3D Voronoi code. We also thank the Champalimaud
animal facility, Anna Pezzarossa and the Champalimaud ABBE platform for the help
with microscopy and image processing. This work was supported by EMBO (ALTF 522-2021),
a Fundação para a Ciência e Tecnologia grant to A.S.D. (PTDC/MED-ONC/5553/2020),
as well as the European Research Council (grant 851288 to EH). A.S.D., S.C., and
R.M.S. are supported by QuantOCancer Project Horizon European Union’s Horizon 2020
program (grant agreement No 810653).
article_number: '8440'
article_processing_charge: Yes
article_type: original
author:
- first_name: Preeti
full_name: Sahu, Preeti
id: 55BA52EE-A185-11EA-88FD-18AD3DDC885E
last_name: Sahu
- first_name: Sara
full_name: Monteiro-Ferreira, Sara
last_name: Monteiro-Ferreira
- first_name: Sara
full_name: Canato, Sara
last_name: Canato
- first_name: Raquel Maia
full_name: Soares, Raquel Maia
last_name: Soares
- first_name: Adriana
full_name: Sánchez-Danés, Adriana
last_name: Sánchez-Danés
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
citation:
ama: Sahu P, Monteiro-Ferreira S, Canato S, Soares RM, Sánchez-Danés A, Hannezo
EB. Mechanical control of cell fate decisions in the skin epidermis. Nature
Communications. 2025;16. doi:10.1038/s41467-025-62882-9
apa: Sahu, P., Monteiro-Ferreira, S., Canato, S., Soares, R. M., Sánchez-Danés,
A., & Hannezo, E. B. (2025). Mechanical control of cell fate decisions in
the skin epidermis. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-025-62882-9
chicago: Sahu, Preeti, Sara Monteiro-Ferreira, Sara Canato, Raquel Maia Soares,
Adriana Sánchez-Danés, and Edouard B Hannezo. “Mechanical Control of Cell Fate
Decisions in the Skin Epidermis.” Nature Communications. Springer Nature,
2025. https://doi.org/10.1038/s41467-025-62882-9.
ieee: P. Sahu, S. Monteiro-Ferreira, S. Canato, R. M. Soares, A. Sánchez-Danés,
and E. B. Hannezo, “Mechanical control of cell fate decisions in the skin epidermis,”
Nature Communications, vol. 16. Springer Nature, 2025.
ista: Sahu P, Monteiro-Ferreira S, Canato S, Soares RM, Sánchez-Danés A, Hannezo
EB. 2025. Mechanical control of cell fate decisions in the skin epidermis. Nature
Communications. 16, 8440.
mla: Sahu, Preeti, et al. “Mechanical Control of Cell Fate Decisions in the Skin
Epidermis.” Nature Communications, vol. 16, 8440, Springer Nature, 2025,
doi:10.1038/s41467-025-62882-9.
short: P. Sahu, S. Monteiro-Ferreira, S. Canato, R.M. Soares, A. Sánchez-Danés,
E.B. Hannezo, Nature Communications 16 (2025).
corr_author: '1'
date_created: 2025-10-05T22:01:34Z
date_published: 2025-09-26T00:00:00Z
date_updated: 2026-05-20T08:52:01Z
day: '26'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1038/s41467-025-62882-9
ec_funded: 1
external_id:
isi:
- '001582555200011'
pmid:
- '41006218'
file:
- access_level: open_access
checksum: d1656576883b23902545328e2d640234
content_type: application/pdf
creator: dernst
date_created: 2025-10-13T12:37:04Z
date_updated: 2025-10-13T12:37:04Z
file_id: '20464'
file_name: 2025_NatureComm_Sahu.pdf
file_size: 2816813
relation: main_file
success: 1
file_date_updated: 2025-10-13T12:37:04Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 628f3fb1-2b32-11ec-9570-83ce778803f7
grant_number: ALTF 522-2021
name: Biomechanics of stem cell fate determination
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mechanical control of cell fate decisions in the skin epidermis
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2025'
...
---
OA_embargo: 6 months
OA_place: publisher
_id: '19456'
abstract:
- lang: eng
text: "Making decisions requires flexibly adapting to changing environments, a process
that\r\ndepends on accurately interpreting current contingencies and integrating
them with\r\npast experience. Two brain regions are particularly critical for
this process, the medial\r\nprefrontal cortex (mPFC) and the hippocampus. Using
contextual information from the\r\nhippocampus, the mPFC selects relevant cognitive
frameworks and suppresses\r\nirrelevant ones to guide appropriate actions. Several
studies have shown that some\r\nmPFC pyramidal neurons become spatially tuned
when spatial information is required\r\nto guide goal-directed behavior. However,
the role of prefrontal spatial representations\r\nin learning and decision making
is not well understood. This work aims to characterize\r\nthe role of mPFC spatial
tuning in supporting a contextual association task. Rats were\r\ntrained to learn
two cue–location associations on a radial arm maze over multiple days,\r\nwhile
we simultaneously recorded from dorsal CA1 of the hippocampus and the\r\nprelimbic
area of the mPFC. We describe a subset of spatially tuned hippocampal and\r\nprefrontal
pyramidal neurons that “flicker” between multiple spatial representations on\r\ndifferent
trials, suggesting dynamic, context-dependent coding. This flickering may\r\nprovide
a substrate for how the network reorganizes in response to task demands,\r\nlikely
by enabling the flexible evaluation of competing representations. "
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
- _id: M-Shop
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Andrea D
full_name: Cumpelik, Andrea D
id: 3F158B32-F248-11E8-B48F-1D18A9856A87
last_name: Cumpelik
orcid: 0000-0003-1727-6612
citation:
ama: Cumpelik AD. The role of prefrontal spatial coding in supporting a contextual
association task. 2025. doi:10.15479/AT-ISTA-19456
apa: Cumpelik, A. D. (2025). The role of prefrontal spatial coding in supporting
a contextual association task. Institute of Science and Technology Austria.
https://doi.org/10.15479/AT-ISTA-19456
chicago: Cumpelik, Andrea D. “The Role of Prefrontal Spatial Coding in Supporting
a Contextual Association Task.” Institute of Science and Technology Austria, 2025.
https://doi.org/10.15479/AT-ISTA-19456.
ieee: A. D. Cumpelik, “The role of prefrontal spatial coding in supporting a contextual
association task,” Institute of Science and Technology Austria, 2025.
ista: Cumpelik AD. 2025. The role of prefrontal spatial coding in supporting a contextual
association task. Institute of Science and Technology Austria.
mla: Cumpelik, Andrea D. The Role of Prefrontal Spatial Coding in Supporting
a Contextual Association Task. Institute of Science and Technology Austria,
2025, doi:10.15479/AT-ISTA-19456.
short: A.D. Cumpelik, The Role of Prefrontal Spatial Coding in Supporting a Contextual
Association Task, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-03-25T11:22:38Z
date_published: 2025-02-18T00:00:00Z
date_updated: 2026-04-07T12:37:58Z
day: '18'
ddc:
- '612'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JoCs
doi: 10.15479/AT-ISTA-19456
file:
- access_level: open_access
checksum: 1c7573303d8e5f6da3eb03d59055390f
content_type: application/pdf
creator: acumpeli
date_created: 2025-03-25T11:07:55Z
date_updated: 2025-09-30T22:30:02Z
embargo: 2025-09-30
file_id: '19457'
file_name: 2025_Thesis_Cumpelik_corrections_PDFA.pdf
file_size: 11869040
relation: main_file
- access_level: closed
checksum: b93265ebd9a53f7a14100d0d48b4ff5b
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: acumpeli
date_created: 2025-03-25T11:08:05Z
date_updated: 2025-09-30T22:30:02Z
embargo_to: open_access
file_id: '19458'
file_name: 2025_Thesis_Cumpelik_corrections.docx
file_size: 20436467
relation: source_file
file_date_updated: 2025-09-30T22:30:02Z
has_accepted_license: '1'
keyword:
- neuroscience
- decision making
- learning
- cognitive flexibility
- medial prefrontal cortex
- hippocampus
- electrophysiology
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: '96'
publication_identifier:
isbn:
- 978-3-99078-056-5
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Jozsef L
full_name: Csicsvari, Jozsef L
id: 3FA14672-F248-11E8-B48F-1D18A9856A87
last_name: Csicsvari
orcid: 0000-0002-5193-4036
title: The role of prefrontal spatial coding in supporting a contextual association
task
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
OA_place: publisher
_id: '19763'
abstract:
- lang: eng
text: "Pattern formation in developing organs is controlled by morphogens. These
signalling\r\nmolecules form concentration gradients across tissues, thereby providing
positional\r\ninformation that instructs the pattern of cell differentiation.
Morphogen gradients are highly\r\ndynamic in space and time. Many factors such
as morphogen production, spreading,\r\ndegradation, cellular rearrangements and
others could contribute to changes in the gradient\r\nshape, yet how the spatiotemporal
signalling dynamics arise in many systems is still unclear.\r\nWe studied the
dynamics of morphogen signalling and tissue patterning in the developing\r\nvertebrate
neural tube. In this system, neural crest, roof plate and distinct dorsal progenitor\r\nsubtypes
are specified in a spatially and temporally ordered manner in response to dorsal-toventral
gradients of BMP and WNT signalling activity. How the BMP and WNT gradients are\r\nestablished
and interpreted to ensure ordered cell specification is poorly understood.\r\nTo
address this question, we developed a 2D embryonic stem cell differentiation system
that\r\ncaptures key features of dorsal neural tube development. In this system,
differentiated\r\ncolonies display remarkable self-organised pattern formation
in response to uniformly\r\napplied BMP ligand. We established a method of differentiating
the colonies using\r\nmicrofabricated stencils, which allowed us to control the
initial size and shape of colonies\r\nwithout confining cell migration and colony
growth. This led to highly reproducible pattern\r\nformation that facilitates
quantification.\r\nUsing this approach, we observed striking two-phase temporal
dynamics of BMP signalling in\r\nour colonies: a BMP gradient rapidly forms from
the periphery to the centre of colonies,\r\nsubsequently disappears and is re-established
again in the second phase. By combining our\r\nquantitative data with a data-driven
theoretical model, we uncovered a temporal relay\r\nmechanism that underlies this
biphasic BMP signalling dynamics. The first signalling phase is\r\ncontrolled
by fast tissue-autonomous negative feedback that restricts the duration of the\r\ninitial
response to BMP. The early BMP activity gradient moreover controls the spatial\r\norganisation
of the cell type pattern: the absence of a first phase results in disordered cell\r\ntype
pattern. The second phase is controlled by slow positive regulation of BMP signalling
by\r\nthe transcription factor LMX1A, a key regulator of roof plate identity.
WNT promotes the\r\nsecond phase of BMP signalling via positive feedback on LMX1A.\r\nAltogether,
the mechanism that we uncovered ensures the coupling of sequential\r\ndevelopmental
events, making pattern formation spatially and temporally organised.\r\nFurthermore,
this mechanism allows the BMP signalling pathway to be reused in different\r\ncontexts
– first for the establishment of the neural plate border, and subsequently for
dorsal\r\nneural progenitor patterning. Our study supports a general developmental
principle in which\r\nmultiple morphogens interact with transcriptional networks
resulting in complex\r\nspatiotemporal signalling dynamics that ultimately drive
organised pattern formation."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
acknowledgement: "My work would also not have been possible without the Imaging and
Optics, the Life Science\r\nand the Preclinical Facility of ISTA. Your support has
facilitated my research substantially. I\r\nalso want to thank the Graduate School
Office for their never-ending support and their sincere\r\neffort to improve the
PhD programme of the ISTA even further.\r\nThis work was supported by the Gesellschaft
für Forschungsförderung Niederösterreich\r\nm.b.H. fellowship (SC19-011). Thank
you for recognizing the importance of this project."
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neural tube. 2025. doi:10.15479/AT-ISTA-19763
apa: Rus, S. (2025). Dynamics of morphogen signalling and cell fate decisions
in the dorsal neural tube. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-19763
chicago: Rus, Stefanie. “Dynamics of Morphogen Signalling and Cell Fate Decisions
in the Dorsal Neural Tube.” Institute of Science and Technology Austria, 2025.
https://doi.org/10.15479/AT-ISTA-19763.
ieee: S. Rus, “Dynamics of morphogen signalling and cell fate decisions in the dorsal
neural tube,” Institute of Science and Technology Austria, 2025.
ista: Rus S. 2025. Dynamics of morphogen signalling and cell fate decisions in the
dorsal neural tube. Institute of Science and Technology Austria.
mla: Rus, Stefanie. Dynamics of Morphogen Signalling and Cell Fate Decisions
in the Dorsal Neural Tube. Institute of Science and Technology Austria, 2025,
doi:10.15479/AT-ISTA-19763.
short: S. Rus, Dynamics of Morphogen Signalling and Cell Fate Decisions in the Dorsal
Neural Tube, Institute of Science and Technology Austria, 2025.
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A thalamic hub-and-spoke network enables visual perception during action by coordinating
visuomotor dynamics. 2024. doi:10.15479/AT:ISTA:18579
apa: Vega Zuniga, T. A., Sumser, A. L., Symonova, O., Koppensteiner, P., Schmidt,
F., & Jösch, M. A. (2024). A thalamic hub-and-spoke network enables visual
perception during action by coordinating visuomotor dynamics. Institute of Science
and Technology Austria. https://doi.org/10.15479/AT:ISTA:18579
chicago: Vega Zuniga, Tomas A, Anton L Sumser, Olga Symonova, Peter Koppensteiner,
Florian Schmidt, and Maximilian A Jösch. “A Thalamic Hub-and-Spoke Network Enables
Visual Perception during Action by Coordinating Visuomotor Dynamics.” Institute
of Science and Technology Austria, 2024. https://doi.org/10.15479/AT:ISTA:18579.
ieee: T. A. Vega Zuniga, A. L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt,
and M. A. Jösch, “A thalamic hub-and-spoke network enables visual perception during
action by coordinating visuomotor dynamics.” Institute of Science and Technology
Austria, 2024.
ista: Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA.
2024. A thalamic hub-and-spoke network enables visual perception during action
by coordinating visuomotor dynamics, Institute of Science and Technology Austria,
10.15479/AT:ISTA:18579.
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Perception during Action by Coordinating Visuomotor Dynamics. Institute of
Science and Technology Austria, 2024, doi:10.15479/AT:ISTA:18579.
short: T.A. Vega Zuniga, A.L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt,
M.A. Jösch, (2024).
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