---
_id: '10614'
abstract:
- lang: eng
text: 'The infiltration of immune cells into tissues underlies the establishment
of tissue-resident macrophages and responses to infections and tumors. Yet the
mechanisms immune cells utilize to negotiate tissue barriers in living organisms
are not well understood, and a role for cortical actin has not been examined.
Here, we find that the tissue invasion of Drosophila macrophages, also known as
plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated
by the Drosophila member of the fos proto oncogene transcription factor family
(Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances
F-actin levels around the entire macrophage surface by increasing mRNA levels
of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking
filamin Cheerio, which are themselves required for invasion. Both the filamin
and the tetraspanin enhance the cortical activity of Rho1 and the formin Diaphanous
and thus the assembly of cortical actin, which is a critical function since expressing
a dominant active form of Diaphanous can rescue the Dfos macrophage invasion defect.
In vivo imaging shows that Dfos enhances the efficiency of the initial phases
of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program
in macrophages counteracts the constraint produced by the tension of surrounding
tissues and buffers the properties of the macrophage nucleus from affecting tissue
entry. We thus identify strengthening the cortical actin cytoskeleton through
Dfos as a key process allowing efficient forward movement of an immune cell into
surrounding tissues. '
acknowledged_ssus:
- _id: LifeSc
acknowledgement: 'We thank the following for their contributions: Plasmids were supplied
by the Drosophila Genomics Resource Center (NIH 2P40OD010949-10A1); fly stocks were
provided by K. Brueckner, B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington
Drosophila Stock Center (NIH P40OD018537) and the Vienna Drosophila Resource Center,
FlyBase for essential genomic information, and the BDGP in situ database for data.
For antibodies, we thank the Developmental Studies Hybridoma Bank, which was created
by the Eunice Kennedy Shriver National Institute of Child Health and Human Development
of the NIH and is maintained at the University of Iowa, as well as J. Zeitlinger
for her generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities
for RNA sequencing and analysis and the Life Scientific Service Units at IST Austria
for technical support and assistance with microscopy and FACS analysis. We thank
C. P. Heisenberg, P. Martin, M. Sixt, and Siekhaus group members for discussions
and T. Hurd, A. Ratheesh, and P. Rangan for comments on the manuscript.'
article_processing_charge: No
article_type: original
author:
- first_name: Vera
full_name: Belyaeva, Vera
id: 47F080FE-F248-11E8-B48F-1D18A9856A87
last_name: Belyaeva
- first_name: Stephanie
full_name: Wachner, Stephanie
id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87
last_name: Wachner
- first_name: Attila
full_name: György, Attila
id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
last_name: György
orcid: 0000-0002-1819-198X
- first_name: Shamsi
full_name: Emtenani, Shamsi
id: 49D32318-F248-11E8-B48F-1D18A9856A87
last_name: Emtenani
orcid: 0000-0001-6981-6938
- first_name: Igor
full_name: Gridchyn, Igor
id: 4B60654C-F248-11E8-B48F-1D18A9856A87
last_name: Gridchyn
orcid: 0000-0002-1807-1929
- first_name: Maria
full_name: Akhmanova, Maria
id: 3425EC26-F248-11E8-B48F-1D18A9856A87
last_name: Akhmanova
orcid: 0000-0003-1522-3162
- first_name: M
full_name: Linder, M
last_name: Linder
- first_name: Marko
full_name: Roblek, Marko
id: 3047D808-F248-11E8-B48F-1D18A9856A87
last_name: Roblek
orcid: 0000-0001-9588-1389
- first_name: M
full_name: Sibilia, M
last_name: Sibilia
- first_name: Daria E
full_name: Siekhaus, Daria E
id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
last_name: Siekhaus
orcid: 0000-0001-8323-8353
citation:
ama: Belyaeva V, Wachner S, György A, et al. Fos regulates macrophage infiltration
against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila.
PLoS Biology. 2022;20(1):e3001494. doi:10.1371/journal.pbio.3001494
apa: Belyaeva, V., Wachner, S., György, A., Emtenani, S., Gridchyn, I., Akhmanova,
M., … Siekhaus, D. E. (2022). Fos regulates macrophage infiltration against surrounding
tissue resistance by a cortical actin-based mechanism in Drosophila. PLoS Biology.
Public Library of Science. https://doi.org/10.1371/journal.pbio.3001494
chicago: Belyaeva, Vera, Stephanie Wachner, Attila György, Shamsi Emtenani, Igor
Gridchyn, Maria Akhmanova, M Linder, Marko Roblek, M Sibilia, and Daria E Siekhaus.
“Fos Regulates Macrophage Infiltration against Surrounding Tissue Resistance by
a Cortical Actin-Based Mechanism in Drosophila.” PLoS Biology. Public Library
of Science, 2022. https://doi.org/10.1371/journal.pbio.3001494.
ieee: V. Belyaeva et al., “Fos regulates macrophage infiltration against
surrounding tissue resistance by a cortical actin-based mechanism in Drosophila,”
PLoS Biology, vol. 20, no. 1. Public Library of Science, p. e3001494, 2022.
ista: Belyaeva V, Wachner S, György A, Emtenani S, Gridchyn I, Akhmanova M, Linder
M, Roblek M, Sibilia M, Siekhaus DE. 2022. Fos regulates macrophage infiltration
against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila.
PLoS Biology. 20(1), e3001494.
mla: Belyaeva, Vera, et al. “Fos Regulates Macrophage Infiltration against Surrounding
Tissue Resistance by a Cortical Actin-Based Mechanism in Drosophila.” PLoS
Biology, vol. 20, no. 1, Public Library of Science, 2022, p. e3001494, doi:10.1371/journal.pbio.3001494.
short: V. Belyaeva, S. Wachner, A. György, S. Emtenani, I. Gridchyn, M. Akhmanova,
M. Linder, M. Roblek, M. Sibilia, D.E. Siekhaus, PLoS Biology 20 (2022) e3001494.
date_created: 2022-01-12T10:18:17Z
date_published: 2022-01-06T00:00:00Z
date_updated: 2024-03-25T23:30:15Z
day: '06'
ddc:
- '570'
department:
- _id: DaSi
- _id: JoCs
doi: 10.1371/journal.pbio.3001494
ec_funded: 1
external_id:
isi:
- '000971223700001'
pmid:
- '34990456'
file:
- access_level: open_access
checksum: f454212a5522a7818ba4b2892315c478
content_type: application/pdf
creator: cchlebak
date_created: 2022-01-12T13:50:04Z
date_updated: 2022-01-12T13:50:04Z
file_id: '10615'
file_name: 2022_PLOSBio_Belyaeva.pdf
file_size: 5426932
relation: main_file
success: 1
file_date_updated: 2022-01-12T13:50:04Z
has_accepted_license: '1'
intvolume: ' 20'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: e3001494
pmid: 1
project:
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29638
name: Drosophila TNFa´s Funktion in Immunzellen
- _id: 26199CA4-B435-11E9-9278-68D0E5697425
grant_number: '24800'
name: Tissue barrier penetration is crucial for immunity and metastasis
- _id: 2536F660-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '334077'
name: Investigating the role of transporters in invasive migration through junctions
publication: PLoS Biology
publication_identifier:
eissn:
- 1545-7885
issn:
- 1544-9173
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
link:
- relation: earlier_version
url: https://www.biorxiv.org/content/10.1101/2020.09.18.301481
- description: News on the ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/resisting-the-pressure/
record:
- id: '8557'
relation: earlier_version
status: public
- id: '11193'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Fos regulates macrophage infiltration against surrounding tissue resistance
by a cortical actin-based mechanism in Drosophila
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 20
year: '2022'
...
---
_id: '10703'
abstract:
- lang: eng
text: 'When crawling through the body, leukocytes often traverse tissues that are
densely packed with extracellular matrix and other cells, and this raises the
question: How do leukocytes overcome compressive mechanical loads? Here, we show
that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness
requires neither force sensing via the nucleus nor adhesive interactions with
a substrate. Upon global compression of the cell body as well as local indentation
of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into
dot-like structures, providing activation platforms for Arp2/3 nucleated actin
patches. These patches locally push against the external load, which can be obstructing
collagen fibers or other cells, and thereby create space to facilitate forward
locomotion. We show in vitro and in vivo that this WASp function is rate limiting
for ameboid leukocyte migration in dense but not in loose environments and is
required for trafficking through diverse tissues such as skin and lymph nodes.'
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner
for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes
Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll
for advice on fluorescent labeling of collagen gels. This research was supported
by the Scientific Service Units (SSUs) of IST Austria through resources provided
by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron
Microscopy Facility. This work was funded by grants from the European Research Council
( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding
from the European Union’s Horizon 2020 research and innovation program under the
Marie Skłodowska-Curie grant agreement no. 747687.
article_processing_charge: No
article_type: original
author:
- first_name: Florian
full_name: Gaertner, Florian
last_name: Gaertner
- first_name: Patricia
full_name: Reis-Rodrigues, Patricia
last_name: Reis-Rodrigues
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Juan
full_name: Aguilera, Juan
last_name: Aguilera
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Aglaja
full_name: Kopf, Aglaja
id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
last_name: Kopf
orcid: 0000-0002-2187-6656
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Vanessa
full_name: Zheden, Vanessa
id: 39C5A68A-F248-11E8-B48F-1D18A9856A87
last_name: Zheden
orcid: 0000-0002-9438-4783
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- 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: Gaertner F, Reis-Rodrigues P, de Vries I, et al. WASp triggers mechanosensitive
actin patches to facilitate immune cell migration in dense tissues. Developmental
Cell. 2022;57(1):47-62.e9. doi:10.1016/j.devcel.2021.11.024
apa: Gaertner, F., Reis-Rodrigues, P., de Vries, I., Hons, M., Aguilera, J., Riedl,
M., … Sixt, M. K. (2022). WASp triggers mechanosensitive actin patches to facilitate
immune cell migration in dense tissues. Developmental Cell. Cell Press ;
Elsevier. https://doi.org/10.1016/j.devcel.2021.11.024
chicago: Gaertner, Florian, Patricia Reis-Rodrigues, Ingrid de Vries, Miroslav Hons,
Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive
Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental
Cell. Cell Press ; Elsevier, 2022. https://doi.org/10.1016/j.devcel.2021.11.024.
ieee: F. Gaertner et al., “WASp triggers mechanosensitive actin patches to
facilitate immune cell migration in dense tissues,” Developmental Cell,
vol. 57, no. 1. Cell Press ; Elsevier, p. 47–62.e9, 2022.
ista: Gaertner F, Reis-Rodrigues P, de Vries I, Hons M, Aguilera J, Riedl M, Leithner
AF, Tasciyan S, Kopf A, Merrin J, Zheden V, Kaufmann W, Hauschild R, Sixt MK.
2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration
in dense tissues. Developmental Cell. 57(1), 47–62.e9.
mla: Gaertner, Florian, et al. “WASp Triggers Mechanosensitive Actin Patches to
Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell,
vol. 57, no. 1, Cell Press ; Elsevier, 2022, p. 47–62.e9, doi:10.1016/j.devcel.2021.11.024.
short: F. Gaertner, P. Reis-Rodrigues, I. de Vries, M. Hons, J. Aguilera, M. Riedl,
A.F. Leithner, S. Tasciyan, A. Kopf, J. Merrin, V. Zheden, W. Kaufmann, R. Hauschild,
M.K. Sixt, Developmental Cell 57 (2022) 47–62.e9.
date_created: 2022-01-30T23:01:33Z
date_published: 2022-01-10T00:00:00Z
date_updated: 2024-03-25T23:30:12Z
day: '10'
ddc:
- '570'
department:
- _id: MiSi
- _id: EM-Fac
- _id: NanoFab
- _id: BjHo
doi: 10.1016/j.devcel.2021.11.024
ec_funded: 1
external_id:
isi:
- '000768933800005'
pmid:
- '34919802'
intvolume: ' 57'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.sciencedirect.com/science/article/pii/S1534580721009497
month: '01'
oa: 1
oa_version: Published Version
page: 47-62.e9
pmid: 1
project:
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '747687'
name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
publication: Developmental Cell
publication_identifier:
eissn:
- 1878-1551
issn:
- 1534-5807
publication_status: published
publisher: Cell Press ; Elsevier
quality_controlled: '1'
related_material:
record:
- id: '12726'
relation: dissertation_contains
status: public
- id: '14530'
relation: dissertation_contains
status: public
- id: '12401'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: WASp triggers mechanosensitive actin patches to facilitate immune cell migration
in dense tissues
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 57
year: '2022'
...
---
_id: '10727'
abstract:
- lang: eng
text: "Social insects are a common model to study disease dynamics in social animals.
Even though pathogens should thrive in social insect colonies as the hosts engage
in frequent social interactions, are closely related and live in a pathogen-rich
environment, disease outbreaks are rare. This is because social insects have evolved
mechanisms to keep pathogens at bay – and fight disease as a collective. Social
insect colonies are often viewed as “superorganisms” with division of labor between
reproductive “germ-like” queens and males and “somatic” workers, which together
form an interdependent reproductive unit that parallels a multicellular body.
Superorganisms possess a “social immune system” that comprises of collective disease
defenses performed by the workers - summarized as “social immunity”. In social
groups immunization (reduced susceptibility to a parasite upon secondary exposure
to the same parasite) can e.g. be triggered by social interactions (“social immunization”).
Social immunization can be caused by (i) asymptomatic low-level infections that
are acquired during caregiving to a contagious individual that can give an immune
boost, which can induce protection upon later encounter with the same pathogen
(active immunization) or (ii) by transfer of immune effectors between individuals
(passive immunization).\r\nIn the second chapter, I built up on a study that I
co-authored that found that low-level infections can not only be protective, but
also be costly and make the host more susceptible to detrimental superinfections
after contact to a very dissimilar pathogen. I here now tested different degrees
of phylogenetically-distant fungal strains of M. brunneum and M. robertsii in
L. neglectus and can describe the occurrence of cross-protection of social immunization
if the first and second pathogen are from the same level. Interestingly, low-level
infections only provided protection when the first strain was less virulent than
the second strain and elicited higher immune gene expression.\r\nIn the third
and fourth chapters, I expanded on the role of social immunity in sexual selection,
a so far unstudied field. I used the fungus Metarhizium robertsii and the ant
Cardiocondyla obscurior as a model, as in this species mating occurs in the presence
of workers and can be studied under laboratory conditions. Before males mate with
virgin queens in the nest they engage in fierce combat over the access to their
mating partners.\r\nFirst, I focused on male-male competition in the third chapter
and found that fighting with a contagious male is costly as it can lead to contamination
of the rival, but that workers can decrease the risk of disease contraction by
performing sanitary care.\r\nIn the fourth chapter, I studied the effect of fungal
infection on survival and mating success of sexuals (freshly emerged queens and
males) and found that worker-performed sanitary care can buffer the negative effect
that a pathogenic contagion would have on sexuals by spore removal from the exposed
individuals. When social immunity was prevented and queens could contract spores
from their mating partner, very low dosages led to negative consequences: their
lifespan was reduced and they produced fewer offspring with poor immunocompetence
compared to healthy queens. Interestingly, cohabitation with a late-stage infected
male where no spore transfer was possible had a positive effect on offspring immunity
– male offspring of mothers that apparently perceived an infected partner in their
vicinity reacted more sensitively to fungal challenge than male offspring without
paternal pathogen history."
acknowledged_ssus:
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Sina
full_name: Metzler, Sina
id: 48204546-F248-11E8-B48F-1D18A9856A87
last_name: Metzler
orcid: 0000-0002-9547-2494
citation:
ama: Metzler S. Pathogen-mediated sexual selection and immunization in ant colonies.
2022. doi:10.15479/AT:ISTA:10727
apa: Metzler, S. (2022). Pathogen-mediated sexual selection and immunization
in ant colonies. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:10727
chicago: Metzler, Sina. “Pathogen-Mediated Sexual Selection and Immunization in
Ant Colonies.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/AT:ISTA:10727.
ieee: S. Metzler, “Pathogen-mediated sexual selection and immunization in ant colonies,”
Institute of Science and Technology Austria, 2022.
ista: Metzler S. 2022. Pathogen-mediated sexual selection and immunization in ant
colonies. Institute of Science and Technology Austria.
mla: Metzler, Sina. Pathogen-Mediated Sexual Selection and Immunization in Ant
Colonies. Institute of Science and Technology Austria, 2022, doi:10.15479/AT:ISTA:10727.
short: S. Metzler, Pathogen-Mediated Sexual Selection and Immunization in Ant Colonies,
Institute of Science and Technology Austria, 2022.
date_created: 2022-02-04T15:45:12Z
date_published: 2022-02-07T00:00:00Z
date_updated: 2023-09-07T13:43:23Z
day: '07'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SyCr
doi: 10.15479/AT:ISTA:10727
ec_funded: 1
file:
- access_level: closed
checksum: 47ba18bb270dd6cc266e0a3f7c69d0e4
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: smetzler
date_created: 2022-02-04T15:36:12Z
date_updated: 2023-02-03T23:30:03Z
embargo_to: open_access
file_id: '10728'
file_name: Thesis_Sina_Metzler.docx
file_size: 6757886
relation: source_file
- access_level: open_access
checksum: f3ec07d5d6b20ae6e46bfeedebce9027
content_type: application/pdf
creator: smetzler
date_created: 2022-02-04T15:36:43Z
date_updated: 2023-02-03T23:30:03Z
embargo: 2023-02-02
file_id: '10730'
file_name: Thesis_Sina_Metzler_A2.pdf
file_size: 6314921
relation: main_file
- access_level: open_access
checksum: dedd14b7be7a75d63018dbfc68dd8113
content_type: application/pdf
creator: smetzler
date_created: 2022-02-07T10:35:02Z
date_updated: 2023-02-04T23:30:03Z
embargo: 2023-02-02
file_id: '10742'
file_name: Thesis_Sina_Metzler_print.pdf
file_size: 6882557
relation: main_file
file_date_updated: 2023-02-04T23:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
project:
- _id: 2649B4DE-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '771402'
name: Epidemics in ant societies on a chip
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Sylvia
full_name: Cremer, Sylvia
id: 2F64EC8C-F248-11E8-B48F-1D18A9856A87
last_name: Cremer
orcid: 0000-0002-2193-3868
title: Pathogen-mediated sexual selection and immunization in ant colonies
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2022'
...
---
_id: '10791'
abstract:
- lang: eng
text: The mammalian neocortex is composed of diverse neuronal and glial cell classes
that broadly arrange in six distinct laminae. Cortical layers emerge during development
and defects in the developmental programs that orchestrate cortical lamination
are associated with neurodevelopmental diseases. The developmental principle of
cortical layer formation depends on concerted radial projection neuron migration,
from their birthplace to their final target position. Radial migration occurs
in defined sequential steps, regulated by a large array of signaling pathways.
However, based on genetic loss-of-function experiments, most studies have thus
far focused on the role of cell-autonomous gene function. Yet, cortical neuron
migration in situ is a complex process and migrating neurons traverse along diverse
cellular compartments and environments. The role of tissue-wide properties and
genetic state in radial neuron migration is however not clear. Here we utilized
mosaic analysis with double markers (MADM) technology to either sparsely or globally
delete gene function, followed by quantitative single-cell phenotyping. The MADM-based
gene ablation paradigms in combination with computational modeling demonstrated
that global tissue-wide effects predominate cell-autonomous gene function albeit
in a gene-specific manner. Our results thus suggest that the genetic landscape
in a tissue critically affects the overall migration phenotype of individual cortical
projection neurons. In a broader context, our findings imply that global tissue-wide
effects represent an essential component of the underlying etiology associated
with focal malformations of cortical development in particular, and neurological
diseases in general.
acknowledged_ssus:
- _id: LifeSc
- _id: PreCl
- _id: Bio
acknowledgement: "A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian
Academy of Sciences. This work also received support from IST Austria institutional
funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh
Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC
funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical
support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer
lab for discussion. This research was supported by the Scientific Service Units
of IST Austria through resources provided by the Imaging and Optics Facility, Lab
Support Facility and Preclinical Facility."
article_number: kvac009
article_processing_charge: No
article_type: original
author:
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Anna-Magdalena
full_name: Heger, Anna-Magdalena
id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
last_name: Heger
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- 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: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
- first_name: Li Huei
full_name: Tsai, Li Huei
last_name: Tsai
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic
gene function in radial neuron migration. Oxford Open Neuroscience. 2022;1(1).
doi:10.1093/oons/kvac009
apa: Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter,
S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene
function in radial neuron migration. Oxford Open Neuroscience. Oxford Academic.
https://doi.org/10.1093/oons/kvac009
chicago: Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena
Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override
Cell-Intrinsic Gene Function in Radial Neuron Migration.” Oxford Open Neuroscience.
Oxford Academic, 2022. https://doi.org/10.1093/oons/kvac009.
ieee: A. H. Hansen et al., “Tissue-wide effects override cell-intrinsic gene
function in radial neuron migration,” Oxford Open Neuroscience, vol. 1,
no. 1. Oxford Academic, 2022.
ista: Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM,
Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects
override cell-intrinsic gene function in radial neuron migration. Oxford Open
Neuroscience. 1(1), kvac009.
mla: Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function
in Radial Neuron Migration.” Oxford Open Neuroscience, vol. 1, no. 1, kvac009,
Oxford Academic, 2022, doi:10.1093/oons/kvac009.
short: A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter,
C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford
Open Neuroscience 1 (2022).
date_created: 2022-02-25T07:52:11Z
date_published: 2022-07-07T00:00:00Z
date_updated: 2023-11-30T10:55:12Z
day: '07'
ddc:
- '570'
department:
- _id: SiHi
- _id: BjHo
- _id: LifeSc
- _id: EM-Fac
doi: 10.1093/oons/kvac009
ec_funded: 1
file:
- access_level: open_access
checksum: 822e76e056c07099d1fb27d1ece5941b
content_type: application/pdf
creator: dernst
date_created: 2023-08-16T08:00:30Z
date_updated: 2023-08-16T08:00:30Z
file_id: '14061'
file_name: 2023_OxfordOpenNeuroscience_Hansen.pdf
file_size: 4846551
relation: main_file
success: 1
file_date_updated: 2023-08-16T08:00:30Z
has_accepted_license: '1'
intvolume: ' 1'
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
publication: Oxford Open Neuroscience
publication_identifier:
eissn:
- 2753-149X
publication_status: published
publisher: Oxford Academic
quality_controlled: '1'
related_material:
record:
- id: '12726'
relation: dissertation_contains
status: public
- id: '14530'
relation: dissertation_contains
status: public
status: public
title: Tissue-wide effects override cell-intrinsic gene function in radial neuron
migration
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: 1
year: '2022'
...
---
_id: '9794'
abstract:
- lang: eng
text: 'Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular
cells that form dedicated niches for immune cell interaction and capsular fibroblasts
that build a shell around the organ. Immunological challenge causes LNs to increase
more than tenfold in size within a few days. Here, we characterized the biomechanics
of LN swelling on the cellular and organ scale. We identified lymphocyte trapping
by influx and proliferation as drivers of an outward pressure force, causing fibroblastic
reticular cells of the T-zone (TRCs) and their associated conduits to stretch.
After an initial phase of relaxation, TRCs sensed the resulting strain through
cell matrix adhesions, which coordinated local growth and remodeling of the stromal
network. While the expanded TRC network readopted its typical configuration, a
massive fibrotic reaction of the organ capsule set in and countered further organ
expansion. Thus, different fibroblast populations mechanically control LN swelling
in a multitier fashion.'
acknowledged_ssus:
- _id: Bio
- _id: EM-Fac
- _id: PreCl
- _id: LifeSc
acknowledgement: This research was supported by the Scientific Service Units of IST
Austria through resources provided by the Imaging and Optics, Electron Microscopy,
Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd
antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing
a custom 3D channel alignment script. This work was supported by a European Research
Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR
20-24603Y and Charles University PRIMUS/20/MED/013.
article_processing_charge: No
article_type: original
author:
- first_name: Frank P
full_name: Assen, Frank P
id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
last_name: Assen
orcid: 0000-0003-3470-6119
- first_name: Jun
full_name: Abe, Jun
last_name: Abe
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Tommaso
full_name: Costanzo, Tommaso
id: D93824F4-D9BA-11E9-BB12-F207E6697425
last_name: Costanzo
orcid: 0000-0001-9732-3815
- first_name: Gabriel
full_name: Krens, Gabriel
id: 2B819732-F248-11E8-B48F-1D18A9856A87
last_name: Krens
orcid: 0000-0003-4761-5996
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Burkhard
full_name: Ludewig, Burkhard
last_name: Ludewig
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
- first_name: Wolfgang
full_name: Weninger, Wolfgang
last_name: Weninger
- 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: Sanjiv A.
full_name: Luther, Sanjiv A.
last_name: Luther
- first_name: Jens V.
full_name: Stein, Jens V.
last_name: Stein
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
citation:
ama: Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations
in swelling lymph nodes. Nature Immunology. 2022;23:1246-1255. doi:10.1038/s41590-022-01257-4
apa: Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W.,
… Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling
lymph nodes. Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-022-01257-4
chicago: Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour,
Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal
Adaptations in Swelling Lymph Nodes.” Nature Immunology. Springer Nature,
2022. https://doi.org/10.1038/s41590-022-01257-4.
ieee: F. P. Assen et al., “Multitier mechanics control stromal adaptations
in swelling lymph nodes,” Nature Immunology, vol. 23. Springer Nature,
pp. 1246–1255, 2022.
ista: Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T,
Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo
EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations
in swelling lymph nodes. Nature Immunology. 23, 1246–1255.
mla: Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in
Swelling Lymph Nodes.” Nature Immunology, vol. 23, Springer Nature, 2022,
pp. 1246–55, doi:10.1038/s41590-022-01257-4.
short: F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T.
Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg,
W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology
23 (2022) 1246–1255.
date_created: 2021-08-06T09:09:11Z
date_published: 2022-07-11T00:00:00Z
date_updated: 2023-08-02T06:53:07Z
day: '11'
ddc:
- '570'
department:
- _id: SiHi
- _id: CaHe
- _id: EdHa
- _id: EM-Fac
- _id: Bio
- _id: MiSi
doi: 10.1038/s41590-022-01257-4
ec_funded: 1
external_id:
isi:
- '000822975900002'
file:
- access_level: open_access
checksum: 628e7b49809f22c75b428842efe70c68
content_type: application/pdf
creator: dernst
date_created: 2022-07-25T07:11:32Z
date_updated: 2022-07-25T07:11:32Z
file_id: '11642'
file_name: 2022_NatureImmunology_Assen.pdf
file_size: 11475325
relation: main_file
success: 1
file_date_updated: 2022-07-25T07:11:32Z
has_accepted_license: '1'
intvolume: ' 23'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1246-1255
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
publication: Nature Immunology
publication_identifier:
eissn:
- 1529-2916
issn:
- 1529-2908
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Multitier mechanics control stromal adaptations in swelling lymph nodes
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 23
year: '2022'
...
---
_id: '10826'
abstract:
- lang: eng
text: Animals that lose one sensory modality often show augmented responses to other
sensory inputs. The mechanisms underpinning this cross-modal plasticity are poorly
understood. We probe such mechanisms by performing a forward genetic screen for
mutants with enhanced O2 perception in Caenorhabditis elegans. Multiple mutants
exhibiting increased O2 responsiveness concomitantly show defects in other sensory
responses. One mutant, qui-1, defective in a conserved NACHT/WD40 protein, abolishes
pheromone-evoked Ca2+ responses in the ADL pheromone-sensing neurons. At the same
time, ADL responsiveness to pre-synaptic input from O2-sensing neurons is heightened
in qui-1, and other sensory defective mutants, resulting in enhanced neurosecretion
although not increased Ca2+ responses. Expressing qui-1 selectively in ADL rescues
both the qui-1 ADL neurosecretory phenotype and enhanced escape from 21% O2. Profiling
ADL neurons in qui-1 mutants highlights extensive changes in gene expression,
notably of many neuropeptide receptors. We show that elevated ADL expression of
the conserved neuropeptide receptor NPR-22 is necessary for enhanced ADL neurosecretion
in qui-1 mutants, and is sufficient to confer increased ADL neurosecretion in
control animals. Sensory loss can thus confer cross-modal plasticity by changing
the peptidergic connectome.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: ScienComp
acknowledgement: "We would like to thank Gemma Chandratillake and Merav Cohen for
identifying mutants and José David Moñino Sánchez for his help on neurosecretion
assays. We are grateful to Kaveh Ashrafi (UCSF), Piali Sengupta (Brandeis), and
the Caenorhabditis Genetic Center (funded by National Institutes of Health Infrastructure
Program P40 OD010440) for strains and reagents ... and Rebecca Butcher (Univ. Florida)
for C9 pheromone. We thank Tim Stevens, Paula Freire-Pritchett, Alastair Crisp,
GurpreetGhattaoraya, and Fabian Amman for help with bioinformatic analysis, Ekaterina
Lashmanova for help with injections, Iris Hardege for strains, and Isabel Beets
(KU Leuven) and members of the de Bono Lab for comments on the manuscript. We thank
the CRUK Cambridge Research Institute Genomics Core for next generation sequencing
and the Flow Cytometry Facility at LMB for FACS. This research was supported by
the Scientific Service Units (SSU) of IST Austria through resources provided by
the Bioimaging Facility (BIF), the Life Science Facility (LSF) and Scientific Computing
(SciCo-p– Bioinformatics).\r\nThis work was supported by the Medical Research Council
UK (Studentship to GV), an\r\nAdvanced ERC grant (269,058 ACMO to MdB), and a Wellcome
Investigator Award (209504/Z/17/Z to MdB)."
article_number: e68040
article_processing_charge: No
article_type: original
author:
- first_name: Giulio
full_name: Valperga, Giulio
id: 67F289DE-0D8F-11EA-9BDD-54AE3DDC885E
last_name: Valperga
- 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: Valperga G, de Bono M. Impairing one sensory modality enhances another by reconfiguring
peptidergic signalling in Caenorhabditis elegans. eLife. 2022;11. doi:10.7554/eLife.68040
apa: Valperga, G., & de Bono, M. (2022). Impairing one sensory modality enhances
another by reconfiguring peptidergic signalling in Caenorhabditis elegans. ELife.
eLife Sciences Publications. https://doi.org/10.7554/eLife.68040
chicago: Valperga, Giulio, and Mario de Bono. “Impairing One Sensory Modality Enhances
Another by Reconfiguring Peptidergic Signalling in Caenorhabditis Elegans.” ELife.
eLife Sciences Publications, 2022. https://doi.org/10.7554/eLife.68040.
ieee: G. Valperga and M. de Bono, “Impairing one sensory modality enhances another
by reconfiguring peptidergic signalling in Caenorhabditis elegans,” eLife,
vol. 11. eLife Sciences Publications, 2022.
ista: Valperga G, de Bono M. 2022. Impairing one sensory modality enhances another
by reconfiguring peptidergic signalling in Caenorhabditis elegans. eLife. 11,
e68040.
mla: Valperga, Giulio, and Mario de Bono. “Impairing One Sensory Modality Enhances
Another by Reconfiguring Peptidergic Signalling in Caenorhabditis Elegans.” ELife,
vol. 11, e68040, eLife Sciences Publications, 2022, doi:10.7554/eLife.68040.
short: G. Valperga, M. de Bono, ELife 11 (2022).
date_created: 2022-03-06T23:01:52Z
date_published: 2022-02-24T00:00:00Z
date_updated: 2023-08-02T14:42:55Z
day: '24'
ddc:
- '570'
department:
- _id: MaDe
doi: 10.7554/eLife.68040
external_id:
isi:
- '000763432300001'
pmid:
- '35201977'
file:
- access_level: open_access
checksum: cc1b9bf866d0f61f965556e0dd03d3ac
content_type: application/pdf
creator: dernst
date_created: 2022-03-07T07:39:25Z
date_updated: 2022-03-07T07:39:25Z
file_id: '10830'
file_name: 2022_eLife_Valperga.pdf
file_size: 4095591
relation: main_file
success: 1
file_date_updated: 2022-03-07T07:39:25Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 23870BE8-32DE-11EA-91FC-C7463DDC885E
grant_number: 209504/A/17/Z
name: Molecular mechanisms of neural circuit function
publication: eLife
publication_identifier:
eissn:
- 2050084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Impairing one sensory modality enhances another by reconfiguring peptidergic
signalling in Caenorhabditis elegans
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2022'
...
---
_id: '10934'
abstract:
- lang: eng
text: 'FtsA is crucial for assembly of the E. coli divisome, as it dynamically links
cytoplasmic FtsZ filaments with transmembrane cell division proteins. FtsA allegedly
initiates cell division by switching from an inactive polymeric to an active monomeric
confirmation, which recruits downstream proteins and stabilizes FtsZ filaments.
Here, we use biochemical reconstitution experiments combined with quantitative
fluorescence microscopy to study divisome activation in vitro. We compare wildtype-FtsA
with FtsA-R286W, a constantly active gain-of-function mutant and find that R286W
outperforms the wildtype protein in replicating FtsZ treadmilling dynamics, stabilizing
FtsZ filaments and recruiting FtsN. We attribute these differences to a faster
membrane exchange of FtsA-R286W and its higher packing density below FtsZ filaments. Using
FRET microscopy, we find that FtsN binding does not compete with, but promotes
FtsA self-interaction. Our findings suggest a model where FtsA always forms dynamic
polymers on the membrane, which re-organize during assembly and activation of
the divisome. '
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We acknowledge members of the Loose laboratory at IST Austria for
helpful discussions—in particular L. Lindorfer for his assistance with cloning and
purifications. We thank J. Löwe and T. Nierhaus (MRC-LMB Cambridge, UK) for sharing
unpublished work and helpful discussions, as well as D. Vavylonis and D. Rutkowski
(Lehigh University, Bethlehem, PA, USA) as well as S. Martin (University of Lausanne,
Switzerland) for sharing their code for FRAP analysis. We are also thankful for
the support by the Scientific Service Units (SSU) of IST Austria through resources
provided by the Imaging and Optics Facility (IOF) and the Lab Support Facility (LSF).
This work was supported by the European Research Council through grant ERC 2015-StG-679239
and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L. and HFSP LT 000824/2016-L4
to N.B. For the purpose of open access, we have applied a CC BY public copyright
licence to any Author Accepted Manuscript version arising from this submission.
article_processing_charge: No
author:
- first_name: Philipp
full_name: Radler, Philipp
id: 40136C2A-F248-11E8-B48F-1D18A9856A87
last_name: Radler
orcid: ' 0000-0001-9198-2182 '
citation:
ama: Radler P. In vitro reconstitution of Escherichia coli divisome activation.
2022. doi:10.15479/AT:ISTA:10934
apa: Radler, P. (2022). In vitro reconstitution of Escherichia coli divisome activation.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:10934
chicago: Radler, Philipp. “In Vitro Reconstitution of Escherichia Coli Divisome
Activation.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/AT:ISTA:10934.
ieee: P. Radler, “In vitro reconstitution of Escherichia coli divisome activation.”
Institute of Science and Technology Austria, 2022.
ista: Radler P. 2022. In vitro reconstitution of Escherichia coli divisome activation,
Institute of Science and Technology Austria, 10.15479/AT:ISTA:10934.
mla: Radler, Philipp. In Vitro Reconstitution of Escherichia Coli Divisome Activation.
Institute of Science and Technology Austria, 2022, doi:10.15479/AT:ISTA:10934.
short: P. Radler, (2022).
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file_size: 4294960000
relation: main_file
success: 1
file_date_updated: 2022-04-22T10:15:19Z
has_accepted_license: '1'
keyword:
- Bacterial cell division
- in vitro reconstitution
- FtsZ
- FtsN
- FtsA
month: '04'
oa: 1
oa_version: Submitted Version
project:
- _id: 2595697A-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '679239'
name: Self-Organization of the Bacterial Cell
- _id: fc38323b-9c52-11eb-aca3-ff8afb4a011d
grant_number: P34607
name: "Understanding bacterial cell division by in vitro\r\nreconstitution"
publisher: Institute of Science and Technology Austria
related_material:
link:
- description: A custom written code (FRAPdiff) to quantify the Off binding rate
and Diffusion coefficient of membrane bound proteins. Written by Christoph Sommer.
relation: software
url: https://doi.org/10.5281/zenodo.6400639
record:
- id: '11373'
relation: used_in_publication
status: public
- id: '14280'
relation: used_in_publication
status: public
status: public
title: In vitro reconstitution of Escherichia coli divisome activation
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11155'
abstract:
- lang: eng
text: The potential of energy filtering and direct electron detection for cryo-electron
microscopy (cryo-EM) has been well documented. Here, we assess the performance
of recently introduced hardware for cryo-electron tomography (cryo-ET) and subtomogram
averaging (STA), an increasingly popular structural determination method for complex
3D specimens. We acquired cryo-ET datasets of EIAV virus-like particles (VLPs)
on two contemporary cryo-EM systems equipped with different energy filters and
direct electron detectors (DED), specifically a Krios G4, equipped with a cold
field emission gun (CFEG), Thermo Fisher Scientific Selectris X energy filter,
and a Falcon 4 DED; and a Krios G3i, with a Schottky field emission gun (XFEG),
a Gatan Bioquantum energy filter, and a K3 DED. We performed constrained cross-correlation-based
STA on equally sized datasets acquired on the respective systems. The resulting
EIAV CA hexamer reconstructions show that both systems perform comparably in the
4–6 Å resolution range based on Fourier-Shell correlation (FSC). In addition,
by employing a recently introduced multiparticle refinement approach, we obtained
a reconstruction of the EIAV CA hexamer at 2.9 Å. Our results demonstrate the
potential of the new generation of energy filters and DEDs for STA, and the effects
of using different processing pipelines on their STA outcomes.
acknowledged_ssus:
- _id: LifeSc
- _id: ScienComp
- _id: EM-Fac
acknowledgement: This work was funded by the Austrian Science Fund (FWF) grant P31445
to F.K.M.S and the National Institute of Allergy and Infectious Diseases under awards
R01AI147890 to R.A.D. This research was also supported by the Scientific Service
Units (SSUs) of IST Austria through resources provided by Scientific Computing (SciComp),
the Life Science Facility (LSF), and the Electron Microscopy Facility (EMF). We
thank Dustin Morado for providing the software SubTOM for data processing. We also
thank William Wan for critical reading of the manuscript and valuable feedback.
article_number: '107852'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Martin
full_name: Obr, Martin
id: 4741CA5A-F248-11E8-B48F-1D18A9856A87
last_name: Obr
- first_name: Wim J.H.
full_name: Hagen, Wim J.H.
last_name: Hagen
- first_name: Robert A.
full_name: Dick, Robert A.
last_name: Dick
- first_name: Lingbo
full_name: Yu, Lingbo
last_name: Yu
- first_name: Abhay
full_name: Kotecha, Abhay
last_name: Kotecha
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
citation:
ama: Obr M, Hagen WJH, Dick RA, Yu L, Kotecha A, Schur FK. Exploring high-resolution
cryo-ET and subtomogram averaging capabilities of contemporary DEDs. Journal
of Structural Biology. 2022;214(2). doi:10.1016/j.jsb.2022.107852
apa: Obr, M., Hagen, W. J. H., Dick, R. A., Yu, L., Kotecha, A., & Schur, F.
K. (2022). Exploring high-resolution cryo-ET and subtomogram averaging capabilities
of contemporary DEDs. Journal of Structural Biology. Elsevier. https://doi.org/10.1016/j.jsb.2022.107852
chicago: Obr, Martin, Wim J.H. Hagen, Robert A. Dick, Lingbo Yu, Abhay Kotecha,
and Florian KM Schur. “Exploring High-Resolution Cryo-ET and Subtomogram Averaging
Capabilities of Contemporary DEDs.” Journal of Structural Biology. Elsevier,
2022. https://doi.org/10.1016/j.jsb.2022.107852.
ieee: M. Obr, W. J. H. Hagen, R. A. Dick, L. Yu, A. Kotecha, and F. K. Schur, “Exploring
high-resolution cryo-ET and subtomogram averaging capabilities of contemporary
DEDs,” Journal of Structural Biology, vol. 214, no. 2. Elsevier, 2022.
ista: Obr M, Hagen WJH, Dick RA, Yu L, Kotecha A, Schur FK. 2022. Exploring high-resolution
cryo-ET and subtomogram averaging capabilities of contemporary DEDs. Journal of
Structural Biology. 214(2), 107852.
mla: Obr, Martin, et al. “Exploring High-Resolution Cryo-ET and Subtomogram Averaging
Capabilities of Contemporary DEDs.” Journal of Structural Biology, vol.
214, no. 2, 107852, Elsevier, 2022, doi:10.1016/j.jsb.2022.107852.
short: M. Obr, W.J.H. Hagen, R.A. Dick, L. Yu, A. Kotecha, F.K. Schur, Journal of
Structural Biology 214 (2022).
date_created: 2022-04-15T07:10:26Z
date_published: 2022-06-01T00:00:00Z
date_updated: 2023-08-03T06:25:23Z
day: '01'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1016/j.jsb.2022.107852
external_id:
isi:
- '000790733600001'
pmid:
- '35351542'
file:
- access_level: open_access
checksum: 0b1eb53447aae8e95ae4c12d193b0b00
content_type: application/pdf
creator: dernst
date_created: 2022-08-02T11:07:58Z
date_updated: 2022-08-02T11:07:58Z
file_id: '11722'
file_name: 2022_JourStructuralBiology_Obr.pdf
file_size: 7080863
relation: main_file
success: 1
file_date_updated: 2022-08-02T11:07:58Z
has_accepted_license: '1'
intvolume: ' 214'
isi: 1
issue: '2'
keyword:
- Structural Biology
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 26736D6A-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P31445
name: Structural conservation and diversity in retroviral capsid
publication: Journal of Structural Biology
publication_identifier:
issn:
- 1047-8477
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Exploring high-resolution cryo-ET and subtomogram averaging capabilities of
contemporary DEDs
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 214
year: '2022'
...
---
_id: '11160'
abstract:
- lang: eng
text: Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent
cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses
macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency
affects neurodevelopmental is unclear. Here, employing human cerebral organoids,
we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories
with an accelerated and delayed generation of, respectively, inhibitory and excitatory
neurons that yields, at days 60 and 120, symmetrically opposite expansions in
their proportions. This imbalance is consistent with an enlargement of cerebral
organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic
design of patient-specific mutations and mosaic organoids, we define genotype-phenotype
relationships and uncover their cell-autonomous nature. Our results define cell-type-specific
CHD8-dependent molecular defects related to an abnormal program of proliferation
and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations,
our study uncovers reproducible developmental alterations that may be employed
for neurodevelopmental disease modeling.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank Farnaz Freeman for technical assistance. This research was
supported by the Scientific Service Units (SSU) of IST Austria through resources
provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This
work supported by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs);
the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele;
and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures
were created using BioRender.com.
article_number: '110615'
article_processing_charge: Yes
article_type: original
author:
- first_name: Carlo Emanuele
full_name: Villa, Carlo Emanuele
last_name: Villa
- first_name: Cristina
full_name: Cheroni, Cristina
last_name: Cheroni
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Alejandro
full_name: López-Tóbon, Alejandro
last_name: López-Tóbon
- first_name: Bárbara
full_name: Oliveira, Bárbara
id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
last_name: Oliveira
- first_name: Roberto
full_name: Sacco, Roberto
id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
last_name: Sacco
- first_name: Aysan Çerağ
full_name: Yahya, Aysan Çerağ
id: 365A65F8-F248-11E8-B48F-1D18A9856A87
last_name: Yahya
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Michele
full_name: Gabriele, Michele
last_name: Gabriele
- 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: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Mariano
full_name: Gabitto, Mariano
last_name: Gabitto
- 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: Giuseppe
full_name: Testa, Giuseppe
last_name: Testa
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism
to transient alterations in excitatory and inhibitory trajectories. Cell Reports.
2022;39(1). doi:10.1016/j.celrep.2022.110615
apa: Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco,
R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations
in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615
chicago: Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon,
Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency
Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.”
Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615.
ieee: C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient
alterations in excitatory and inhibitory trajectories,” Cell Reports, vol.
39, no. 1. Elsevier, 2022.
ista: Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ,
Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG,
Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations
in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.
mla: Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient
Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol.
39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615.
short: C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco,
A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer,
M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).
date_created: 2022-04-15T09:03:10Z
date_published: 2022-04-05T00:00:00Z
date_updated: 2024-03-25T23:30:25Z
day: '05'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
doi: 10.1016/j.celrep.2022.110615
ec_funded: 1
external_id:
isi:
- '000785983900003'
pmid:
- '35385734'
file:
- access_level: open_access
checksum: b4e8d68f0268dec499af333e6fd5d8e1
content_type: application/pdf
creator: dernst
date_created: 2022-04-15T09:06:25Z
date_updated: 2022-04-15T09:06:25Z
file_id: '11164'
file_name: 2022_CellReports_Villa.pdf
file_size: '7808644'
relation: main_file
success: 1
file_date_updated: 2022-04-15T09:06:25Z
has_accepted_license: '1'
intvolume: ' 39'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2690FEAC-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I04205
name: Identification of converging Molecular Pathways Across Chromatinopathies as
Targets for Therapy
publication: Cell Reports
publication_identifier:
issn:
- 2211-1247
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '12364'
relation: dissertation_contains
status: public
status: public
title: CHD8 haploinsufficiency links autism to transient alterations in excitatory
and inhibitory trajectories
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 39
year: '2022'
...
---
_id: '11193'
abstract:
- lang: eng
text: "The infiltration of immune cells into tissues underlies the establishment
of tissue-resident\r\nmacrophages and responses to infections and tumors. However,
the mechanisms immune\r\ncells utilize to collectively migrate through tissue
barriers in vivo are not yet well understood.\r\nIn this thesis, I describe two
mechanisms that Drosophila immune cells (hemocytes) use to\r\novercome the tissue
barrier of the germband in the embryo. One strategy is the strengthening\r\nof
the actin cortex through developmentally controlled transcriptional regulation
induced by\r\nthe Drosophila proto-oncogene family member Dfos, which I show in
Chapter 2. Dfos induces\r\nexpression of the tetraspanin TM4SF and the filamin
Cher leading to higher levels of the\r\nactivated formin Dia at the cortex and
increased cortical F-actin. This enhanced cortical\r\nstrength allows hemocytes
to overcome the physical resistance of the surrounding tissue and\r\ntranslocate
their nucleus to move forward. This mechanism affects the speed of migration\r\nwhen
hemocytes face a confined environment in vivo.\r\nAnother aspect of the invasion
process is the initial step of the leading hemocytes entering\r\nthe tissue, which
potentially guides the follower cells. In Chapter 3, I describe a novel\r\nsubpopulation
of hemocytes activated by BMP signaling prior to tissue invasion that leads\r\npenetration
into the germband. Hemocytes that are deficient in BMP signaling activation\r\nshow
impaired persistence at the tissue entry, while their migration speed remains\r\nunaffected.\r\nThis
suggests that there might be different mechanisms controlling immune cell migration\r\nwithin
the confined environment in vivo, one of these being the general ability to overcome\r\nthe
resistance of the surrounding tissue and another affecting the order of hemocytes
that\r\ncollectively invade the tissue in a stream of individual cells.\r\nTogether,
my findings provide deeper insights into transcriptional changes in immune\r\ncells
that enable efficient tissue invasion and pave the way for future studies investigating
the\r\nearly colonization of tissues by macrophages in higher organisms. Moreover,
they extend the\r\ncurrent view of Drosophila immune cell heterogeneity and point
toward a potentially\r\nconserved role for canonical BMP signaling in specifying
immune cells that lead the migration\r\nof tissue resident macrophages during
embryogenesis."
acknowledged_ssus:
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Stephanie
full_name: Wachner, Stephanie
id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87
last_name: Wachner
citation:
ama: Wachner S. Transcriptional regulation by Dfos and BMP-signaling support tissue
invasion of Drosophila immune cells. 2022. doi:10.15479/at:ista:11193
apa: Wachner, S. (2022). Transcriptional regulation by Dfos and BMP-signaling
support tissue invasion of Drosophila immune cells. Institute of Science and
Technology Austria. https://doi.org/10.15479/at:ista:11193
chicago: Wachner, Stephanie. “Transcriptional Regulation by Dfos and BMP-Signaling
Support Tissue Invasion of Drosophila Immune Cells.” Institute of Science and
Technology Austria, 2022. https://doi.org/10.15479/at:ista:11193.
ieee: S. Wachner, “Transcriptional regulation by Dfos and BMP-signaling support
tissue invasion of Drosophila immune cells,” Institute of Science and Technology
Austria, 2022.
ista: Wachner S. 2022. Transcriptional regulation by Dfos and BMP-signaling support
tissue invasion of Drosophila immune cells. Institute of Science and Technology
Austria.
mla: Wachner, Stephanie. Transcriptional Regulation by Dfos and BMP-Signaling
Support Tissue Invasion of Drosophila Immune Cells. Institute of Science and
Technology Austria, 2022, doi:10.15479/at:ista:11193.
short: S. Wachner, Transcriptional Regulation by Dfos and BMP-Signaling Support
Tissue Invasion of Drosophila Immune Cells, Institute of Science and Technology
Austria, 2022.
date_created: 2022-04-20T08:59:07Z
date_published: 2022-04-20T00:00:00Z
date_updated: 2023-09-19T10:15:54Z
day: '20'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: DaSi
doi: 10.15479/at:ista:11193
file:
- access_level: open_access
checksum: 999ab16884c4522486136ebc5ae8dbff
content_type: application/pdf
creator: cchlebak
date_created: 2022-04-20T09:03:57Z
date_updated: 2023-04-21T22:30:03Z
embargo: 2023-04-20
file_id: '11195'
file_name: Thesis_Stephanie_Wachner_20200414_formatted.pdf
file_size: 8820951
relation: main_file
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checksum: fd92b1e38d53bdf8b458213882d41383
content_type: application/x-zip-compressed
creator: cchlebak
date_created: 2022-04-22T12:41:00Z
date_updated: 2023-04-21T22:30:03Z
embargo_to: open_access
file_id: '11329'
file_name: Thesis_Stephanie_Wachner_20200414.zip
file_size: 65864612
relation: source_file
file_date_updated: 2023-04-21T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: '170'
project:
- _id: 26199CA4-B435-11E9-9278-68D0E5697425
grant_number: '24800'
name: Tissue barrier penetration is crucial for immunity and metastasis
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '10614'
relation: part_of_dissertation
status: public
- id: '544'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Daria E
full_name: Siekhaus, Daria E
id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
last_name: Siekhaus
orcid: 0000-0001-8323-8353
title: Transcriptional regulation by Dfos and BMP-signaling support tissue invasion
of Drosophila immune cells
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '11336'
abstract:
- lang: eng
text: The generation of a correctly-sized cerebral cortex with all-embracing neuronal
and glial cell-type diversity critically depends on faithful radial glial progenitor
(RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression
is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity
results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene
expression instructs RGP lineage progression is unknown. Here we utilize Mosaic
Analysis with Double Markers (MADM)-based single cell technology and demonstrate
that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts
at the global tissue-wide level. Conversely, cortical astrocyte production and
maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation.
We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression
that are dependent on complex interplays between intrinsic and tissue-wide properties.
In a broader context our results imply a critical role for the genetic and cellular
niche environment in neural stem cell behavior.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit) and S. Gharagozlou for technical support. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics
Facility (IOF), Lab Support Facility (LSF), and Preclinical Facility (PCF). N.A.
received funding from the FWF Firnberg-Programm (T 1031). The work was supported by IST institutional funds and by the European Research Council (ERC) under the European Union’s Horizon
2020 research and innovation program (grant agreement 725780 LinPro) to S.H.
article_number: abq1263
article_processing_charge: No
article_type: original
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Amberg N, Pauler F, Streicher C, Hippenmeyer S. Tissue-wide genetic and cellular
landscape shapes the execution of sequential PRC2 functions in neural stem cell
lineage progression. Science Advances. 2022;8(44). doi:10.1126/sciadv.abq1263
apa: Amberg, N., Pauler, F., Streicher, C., & Hippenmeyer, S. (2022). Tissue-wide
genetic and cellular landscape shapes the execution of sequential PRC2 functions
in neural stem cell lineage progression. Science Advances. American Association
for the Advancement of Science. https://doi.org/10.1126/sciadv.abq1263
chicago: Amberg, Nicole, Florian Pauler, Carmen Streicher, and Simon Hippenmeyer.
“Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential
PRC2 Functions in Neural Stem Cell Lineage Progression.” Science Advances.
American Association for the Advancement of Science, 2022. https://doi.org/10.1126/sciadv.abq1263.
ieee: N. Amberg, F. Pauler, C. Streicher, and S. Hippenmeyer, “Tissue-wide genetic
and cellular landscape shapes the execution of sequential PRC2 functions in neural
stem cell lineage progression,” Science Advances, vol. 8, no. 44. American
Association for the Advancement of Science, 2022.
ista: Amberg N, Pauler F, Streicher C, Hippenmeyer S. 2022. Tissue-wide genetic
and cellular landscape shapes the execution of sequential PRC2 functions in neural
stem cell lineage progression. Science Advances. 8(44), abq1263.
mla: Amberg, Nicole, et al. “Tissue-Wide Genetic and Cellular Landscape Shapes the
Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.”
Science Advances, vol. 8, no. 44, abq1263, American Association for the
Advancement of Science, 2022, doi:10.1126/sciadv.abq1263.
short: N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022).
date_created: 2022-04-26T15:04:50Z
date_published: 2022-11-01T00:00:00Z
date_updated: 2023-05-31T12:24:10Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1126/sciadv.abq1263
ec_funded: 1
file:
- access_level: open_access
checksum: 0117023e188542082ca6693cf39e7f03
content_type: application/pdf
creator: patrickd
date_created: 2023-03-21T14:18:10Z
date_updated: 2023-03-21T14:18:10Z
file_id: '12742'
file_name: sciadv.abq1263.pdf
file_size: 2973998
relation: main_file
success: 1
file_date_updated: 2023-03-21T14:18:10Z
has_accepted_license: '1'
intvolume: ' 8'
issue: '44'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
publication: Science Advances
publication_identifier:
issn:
- 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/
scopus_import: '1'
status: public
title: Tissue-wide genetic and cellular landscape shapes the execution of sequential
PRC2 functions in neural stem cell lineage progression
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: '2022'
...
---
_id: '11341'
abstract:
- lang: eng
text: Intragenic regions that are removed during maturation of the RNA transcript—introns—are
universally present in the nuclear genomes of eukaryotes1. The budding yeast,
an otherwise intron-poor species, preserves two sets of ribosomal protein genes
that differ primarily in their introns2,3. Although studies have shed light on
the role of ribosomal protein introns under stress and starvation4,5,6, understanding
the contribution of introns to ribosome regulation remains challenging. Here,
by combining isogrowth profiling7 with single-cell protein measurements8, we show
that introns can mediate inducible phenotypic heterogeneity that confers a clear
fitness advantage. Osmotic stress leads to bimodal expression of the small ribosomal
subunit protein Rps22B, which is mediated by an intron in the 5′ untranslated
region of its transcript. The two resulting yeast subpopulations differ in their
ability to cope with starvation. Low levels of Rps22B protein result in prolonged
survival under sustained starvation, whereas high levels of Rps22B enable cells
to grow faster after transient starvation. Furthermore, yeasts growing at high
concentrations of sugar, similar to those in ripe grapes, exhibit bimodal expression
of Rps22B when approaching the stationary phase. Differential intron-mediated
regulation of ribosomal protein genes thus provides a way to diversify the population
when starvation threatens in natural environments. Our findings reveal a role
for introns in inducing phenotypic heterogeneity in changing environments, and
suggest that duplicated ribosomal protein genes in yeast contribute to resolving
the evolutionary conflict between precise expression control and environmental
responsiveness9.
acknowledged_ssus:
- _id: LifeSc
- _id: M-Shop
- _id: Bio
acknowledgement: We thank the IST Austria Life Science Facility, the Miba Machine
Shop and M. Lukačišinová for support with the liquid handling robot; the Bioimaging
Facility at IST Austria, J. Power and B. Meier at the University of Cologne, and
C. Göttlinger at the FACS Analysis Facility at the Institute for Genetics, University
of Cologne, for support with flow cytometry experiments; L. Horst for the development
of the automated experimental methods in Cologne; J. Parenteau, S. Abou Elela, G.
Stormo, M. Springer and M. Schuldiner for providing us with yeast strains; B. Fernando,
T. Fink, G. Ansmann and G. Chevreau for technical support; H. Köver, G. Tkačik,
N. Barton, A. Angermayr and B. Kavčič for support during laboratory relocation;
D. Siekhaus, M. Springer and all the members of the Bollenbach group for support
and discussions; and K. Mitosch, M. Lukačišinová, G. Liti and A. de Luna for critical
reading of our manuscript. This work was supported in part by an Austrian Science
Fund (FWF) standalone grant P 27201-B22 (to T.B.), HFSP program Grant RGP0042/2013
(to T.B.), EU Marie Curie Career Integration Grant No. 303507, and German Research
Foundation (DFG) Collaborative Research Centre (SFB) 1310 (to T.B.). A.E.-C. was
supported by a Georg Forster fellowship from the Alexander von Humboldt Foundation.
article_processing_charge: No
article_type: original
author:
- first_name: Martin
full_name: Lukacisin, Martin
id: 298FFE8C-F248-11E8-B48F-1D18A9856A87
last_name: Lukacisin
orcid: 0000-0001-6549-4177
- first_name: Adriana
full_name: Espinosa-Cantú, Adriana
last_name: Espinosa-Cantú
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Lukacisin M, Espinosa-Cantú A, Bollenbach MT. Intron-mediated induction of
phenotypic heterogeneity. Nature. 2022;605:113-118. doi:10.1038/s41586-022-04633-0
apa: Lukacisin, M., Espinosa-Cantú, A., & Bollenbach, M. T. (2022). Intron-mediated
induction of phenotypic heterogeneity. Nature. Springer Nature. https://doi.org/10.1038/s41586-022-04633-0
chicago: Lukacisin, Martin, Adriana Espinosa-Cantú, and Mark Tobias Bollenbach.
“Intron-Mediated Induction of Phenotypic Heterogeneity.” Nature. Springer
Nature, 2022. https://doi.org/10.1038/s41586-022-04633-0.
ieee: M. Lukacisin, A. Espinosa-Cantú, and M. T. Bollenbach, “Intron-mediated induction
of phenotypic heterogeneity,” Nature, vol. 605. Springer Nature, pp. 113–118,
2022.
ista: Lukacisin M, Espinosa-Cantú A, Bollenbach MT. 2022. Intron-mediated induction
of phenotypic heterogeneity. Nature. 605, 113–118.
mla: Lukacisin, Martin, et al. “Intron-Mediated Induction of Phenotypic Heterogeneity.”
Nature, vol. 605, Springer Nature, 2022, pp. 113–18, doi:10.1038/s41586-022-04633-0.
short: M. Lukacisin, A. Espinosa-Cantú, M.T. Bollenbach, Nature 605 (2022) 113–118.
date_created: 2022-05-01T22:01:42Z
date_published: 2022-05-05T00:00:00Z
date_updated: 2023-08-03T06:44:50Z
day: '05'
ddc:
- '570'
doi: 10.1038/s41586-022-04633-0
ec_funded: 1
external_id:
isi:
- '000784934100003'
pmid:
- '35444278'
file:
- access_level: open_access
checksum: d68cd1596bb9fd819b750fe47c8a138a
content_type: application/pdf
creator: dernst
date_created: 2022-08-05T06:08:24Z
date_updated: 2022-08-05T06:08:24Z
file_id: '11727'
file_name: 2022_Nature_Lukacisin.pdf
file_size: 25360311
relation: main_file
success: 1
file_date_updated: 2022-08-05T06:08:24Z
has_accepted_license: '1'
intvolume: ' 605'
isi: 1
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: 113-118
pmid: 1
project:
- _id: 25E83C2C-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '303507'
name: Optimality principles in responses to antibiotics
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Intron-mediated induction of phenotypic heterogeneity
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 605
year: '2022'
...
---
_id: '11373'
abstract:
- lang: eng
text: The actin-homologue FtsA is essential for E. coli cell division, as it links
FtsZ filaments in the Z-ring to transmembrane proteins. FtsA is thought to initiate
cell constriction by switching from an inactive polymeric to an active monomeric
conformation, which recruits downstream proteins and stabilizes the Z-ring. However,
direct biochemical evidence for this mechanism is missing. Here, we use reconstitution
experiments and quantitative fluorescence microscopy to study divisome activation
in vitro. By comparing wild-type FtsA with FtsA R286W, we find that this hyperactive
mutant outperforms FtsA WT in replicating FtsZ treadmilling dynamics, FtsZ filament
stabilization and recruitment of FtsN. We could attribute these differences to
a faster exchange and denser packing of FtsA R286W below FtsZ filaments. Using
FRET microscopy, we also find that FtsN binding promotes FtsA self-interaction.
We propose that in the active divisome FtsA and FtsN exist as a dynamic copolymer
that follows treadmilling filaments of FtsZ.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We acknowledge members of the Loose laboratory at IST Austria for
helpful discussions—in particular L. Lindorfer for his assistance with cloning and
purifications. We thank J. Löwe and T. Nierhaus (MRC-LMB Cambridge, UK) for sharing
unpublished work and helpful discussions, as well as D. Vavylonis and D. Rutkowski
(Lehigh University, Bethlehem, PA, USA) and S. Martin (University of Lausanne, Switzerland)
for sharing their code for FRAP analysis. We are also thankful for the support by
the Scientific Service Units (SSU) of IST Austria through resources provided by
the Imaging and Optics Facility (IOF) and the Lab Support Facility (LSF). This work
was supported by the European Research Council through grant ERC 2015-StG-679239
and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L. and HFSP LT 000824/2016-L4
to N.B. For the purpose of open access, we have applied a CC BY public copyright
licence to any Author Accepted Manuscript version arising from this submission.
article_number: '2635'
article_processing_charge: No
article_type: original
author:
- first_name: Philipp
full_name: Radler, Philipp
id: 40136C2A-F248-11E8-B48F-1D18A9856A87
last_name: Radler
orcid: '0000-0001-9198-2182 '
- first_name: Natalia S.
full_name: Baranova, Natalia S.
id: 38661662-F248-11E8-B48F-1D18A9856A87
last_name: Baranova
orcid: 0000-0002-3086-9124
- first_name: Paulo R
full_name: Dos Santos Caldas, Paulo R
id: 38FCDB4C-F248-11E8-B48F-1D18A9856A87
last_name: Dos Santos Caldas
orcid: 0000-0001-6730-4461
- 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: Maria D
full_name: Lopez Pelegrin, Maria D
id: 319AA9CE-F248-11E8-B48F-1D18A9856A87
last_name: Lopez Pelegrin
- first_name: David
full_name: Michalik, David
id: B9577E20-AA38-11E9-AC9A-0930E6697425
last_name: Michalik
- first_name: Martin
full_name: Loose, Martin
id: 462D4284-F248-11E8-B48F-1D18A9856A87
last_name: Loose
orcid: 0000-0001-7309-9724
citation:
ama: Radler P, Baranova NS, Dos Santos Caldas PR, et al. In vitro reconstitution
of Escherichia coli divisome activation. Nature Communications. 2022;13.
doi:10.1038/s41467-022-30301-y
apa: Radler, P., Baranova, N. S., Dos Santos Caldas, P. R., Sommer, C. M., Lopez
Pelegrin, M. D., Michalik, D., & Loose, M. (2022). In vitro reconstitution
of Escherichia coli divisome activation. Nature Communications. Springer
Nature. https://doi.org/10.1038/s41467-022-30301-y
chicago: Radler, Philipp, Natalia S. Baranova, Paulo R Dos Santos Caldas, Christoph
M Sommer, Maria D Lopez Pelegrin, David Michalik, and Martin Loose. “In Vitro
Reconstitution of Escherichia Coli Divisome Activation.” Nature Communications.
Springer Nature, 2022. https://doi.org/10.1038/s41467-022-30301-y.
ieee: P. Radler et al., “In vitro reconstitution of Escherichia coli divisome
activation,” Nature Communications, vol. 13. Springer Nature, 2022.
ista: Radler P, Baranova NS, Dos Santos Caldas PR, Sommer CM, Lopez Pelegrin MD,
Michalik D, Loose M. 2022. In vitro reconstitution of Escherichia coli divisome
activation. Nature Communications. 13, 2635.
mla: Radler, Philipp, et al. “In Vitro Reconstitution of Escherichia Coli Divisome
Activation.” Nature Communications, vol. 13, 2635, Springer Nature, 2022,
doi:10.1038/s41467-022-30301-y.
short: P. Radler, N.S. Baranova, P.R. Dos Santos Caldas, C.M. Sommer, M.D. Lopez
Pelegrin, D. Michalik, M. Loose, Nature Communications 13 (2022).
date_created: 2022-05-13T09:06:28Z
date_published: 2022-05-12T00:00:00Z
date_updated: 2024-02-21T12:35:18Z
day: '12'
ddc:
- '570'
department:
- _id: MaLo
doi: 10.1038/s41467-022-30301-y
ec_funded: 1
external_id:
isi:
- '000795171100037'
file:
- access_level: open_access
checksum: 5af863ee1b95a0710f6ee864d68dc7a6
content_type: application/pdf
creator: dernst
date_created: 2022-05-13T09:10:51Z
date_updated: 2022-05-13T09:10:51Z
file_id: '11374'
file_name: 2022_NatureCommunications_Radler.pdf
file_size: 6945191
relation: main_file
success: 1
file_date_updated: 2022-05-13T09:10:51Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
keyword:
- General Physics and Astronomy
- General Biochemistry
- Genetics and Molecular Biology
- General Chemistry
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 2595697A-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '679239'
name: Self-Organization of the Bacterial Cell
- _id: fc38323b-9c52-11eb-aca3-ff8afb4a011d
grant_number: P34607
name: "Understanding bacterial cell division by in vitro\r\nreconstitution"
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1038/s41467-022-34485-1
record:
- id: '14280'
relation: dissertation_contains
status: public
- id: '10934'
relation: research_data
status: public
scopus_import: '1'
status: public
title: In vitro reconstitution of Escherichia coli divisome activation
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2022'
...
---
_id: '11448'
abstract:
- lang: eng
text: Studies of protein fitness landscapes reveal biophysical constraints guiding
protein evolution and empower prediction of functional proteins. However, generalisation
of these findings is limited due to scarceness of systematic data on fitness landscapes
of proteins with a defined evolutionary relationship. We characterized the fitness
peaks of four orthologous fluorescent proteins with a broad range of sequence
divergence. While two of the four studied fitness peaks were sharp, the other
two were considerably flatter, being almost entirely free of epistatic interactions.
Mutationally robust proteins, characterized by a flat fitness peak, were not optimal
templates for machine-learning-driven protein design – instead, predictions were
more accurate for fragile proteins with epistatic landscapes. Our work paves insights
for practical application of fitness landscape heterogeneity in protein engineering.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
acknowledgement: "We thank Ondřej Draganov, Rodrigo Redondo, Bor Kavčič, Mia Juračić
and Andrea Pauli for discussion and technical advice. We thank Anita Testa Salmazo
for advice on resin protein purification, Dmitry Bolotin and the Milaboratory (milaboratory.com)
for access to computing and storage infrastructure, and Josef Houser and Eva Fujdiarova
for technical assistance and data interpretation. Core facility Biomolecular Interactions
and Crystallization of CEITEC Masaryk University is gratefully acknowledged for
the obtaining of the scientific data presented in this paper. This research was
supported by the Scientific Service Units (SSU) of IST-Austria\r\nthrough resources
provided by the Bioimaging Facility (BIF), and the Life Science Facility (LSF).
MiSeq and HiSeq NGS sequencing was performed by the Next Generation Sequencing Facility
at Vienna BioCenter Core Facilities (VBCF), member of the Vienna BioCenter (VBC),
Austria. FACS was performed at the BioOptics Facility of the Institute of Molecular
Pathology (IMP), Austria. We also thank the Biomolecular Crystallography Facility
in the Vanderbilt University Center for Structural Biology. We are grateful to Joel
M Harp for help with X-ray data collection. This work was supported by the ERC Consolidator
grant to FAK (771209—CharFL). KSS acknowledges support by President’s Grant МК–5405.2021.1.4,
the Imperial College Research Fellowship and the MRC London Institute of Medical
Sciences (UKRI MC-A658-5QEA0).\r\nAF is supported by the Marie Skłodowska-Curie
Fellowship (H2020-MSCA-IF-2019, Grant Agreement No. 898203, Project acronym \"FLINDIP\").
Experiments were partially carried out using equipment provided by the Institute
of Bioorganic Chemistry of the Russian Academy of Sciences Сore Facility (CKP IBCH).
This work was supported by a Russian Science Foundation grant 19-74-10102.This project
has received funding from the European Union’s Horizon 2020 research and innovation
programme under the Marie Skłodowska-Curie Grant Agreement No. 665,385."
article_number: '75842'
article_processing_charge: No
article_type: original
author:
- first_name: Louisa
full_name: Gonzalez Somermeyer, Louisa
id: 4720D23C-F248-11E8-B48F-1D18A9856A87
last_name: Gonzalez Somermeyer
orcid: 0000-0001-9139-5383
- first_name: Aubin
full_name: Fleiss, Aubin
last_name: Fleiss
- first_name: Alexander S
full_name: Mishin, Alexander S
last_name: Mishin
- first_name: Nina G
full_name: Bozhanova, Nina G
last_name: Bozhanova
- first_name: Anna A
full_name: Igolkina, Anna A
last_name: Igolkina
- first_name: Jens
full_name: Meiler, Jens
last_name: Meiler
- first_name: Maria-Elisenda
full_name: Alaball Pujol, Maria-Elisenda
last_name: Alaball Pujol
- first_name: Ekaterina V
full_name: Putintseva, Ekaterina V
last_name: Putintseva
- first_name: Karen S
full_name: Sarkisyan, Karen S
last_name: Sarkisyan
- first_name: Fyodor
full_name: Kondrashov, Fyodor
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP
fitness landscape and data-driven protein design. eLife. 2022;11. doi:10.7554/elife.75842
apa: Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina,
A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape
and data-driven protein design. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.75842
chicago: Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova,
Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva,
Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape
and Data-Driven Protein Design.” ELife. eLife Sciences Publications, 2022.
https://doi.org/10.7554/elife.75842.
ieee: L. Gonzalez Somermeyer et al., “Heterogeneity of the GFP fitness landscape
and data-driven protein design,” eLife, vol. 11. eLife Sciences Publications,
2022.
ista: Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler
J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity
of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842.
mla: Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape
and Data-Driven Protein Design.” ELife, vol. 11, 75842, eLife Sciences
Publications, 2022, doi:10.7554/elife.75842.
short: L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina,
J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov,
ELife 11 (2022).
date_created: 2022-06-18T09:06:59Z
date_published: 2022-05-05T00:00:00Z
date_updated: 2023-08-03T07:20:15Z
day: '05'
ddc:
- '570'
department:
- _id: GradSch
- _id: FyKo
doi: 10.7554/elife.75842
ec_funded: 1
external_id:
isi:
- '000799197200001'
file:
- access_level: open_access
checksum: 7573c28f44028ab0cc81faef30039e44
content_type: application/pdf
creator: dernst
date_created: 2022-06-20T07:44:19Z
date_updated: 2022-06-20T07:44:19Z
file_id: '11454'
file_name: 2022_eLife_Somermeyer.pdf
file_size: 5297213
relation: main_file
success: 1
file_date_updated: 2022-06-20T07:44:19Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 26580278-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '771209'
name: Characterizing the fitness landscape on population and global scales
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Heterogeneity of the GFP fitness landscape and data-driven protein design
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2022'
...
---
_id: '11478'
abstract:
- lang: eng
text: Cerebral organoids differentiated from human-induced pluripotent stem cells
(hiPSC) provide a unique opportunity to investigate brain development. However,
organoids usually lack microglia, brain-resident immune cells, which are present
in the early embryonic brain and participate in neuronal circuit development.
Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3
and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol.
Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented,
3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When
we guide the retinal organoid differentiation with low-dosed BMP4, we prevent
cup development and enhance microglia and 3D-cysts formation. Mass spectrometry
identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed
this microglia-preferred environment also within the unguided protocol, providing
insight into microglial behavior and migration and offer a model to study how
they enter and distribute within the human brain.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank the scientific service units at ISTA, specifically the lab
support facility and imaging & optics facility for their support; Nicolas Armel
for performing the Mass Spectrometry. We thank Alexandra Lang and Tanja Peilnsteiner
for their help in human brain tissue collection, Rouven Schulz for his insights
into the functional assays We thank all members of the Siegert group for constant
feedback on the project and Margaret Maes, Rouven Schulz, and Marco Benevento for
feedback on the manuscript. This project has received funding from the European
Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung
Niederösterreich (grant No. Sc19-017 to V.H.).
article_number: '104580'
article_processing_charge: Yes
article_type: original
author:
- first_name: Katarina
full_name: Bartalska, Katarina
id: 4D883232-F248-11E8-B48F-1D18A9856A87
last_name: Bartalska
- 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: Ryan J
full_name: Cubero, Ryan J
id: 850B2E12-9CD4-11E9-837F-E719E6697425
last_name: Cubero
orcid: 0000-0003-0002-1867
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Rössler, Karl
last_name: Rössler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Bartalska K, Hübschmann V, Korkut M, et al. A systematic characterization of
microglia-like cell occurrence during retinal organoid differentiation. iScience.
2022;25(7). doi:10.1016/j.isci.2022.104580
apa: Bartalska, K., Hübschmann, V., Korkut, M., Cubero, R. J., Venturino, A., Rössler,
K., … Siegert, S. (2022). A systematic characterization of microglia-like cell
occurrence during retinal organoid differentiation. IScience. Elsevier.
https://doi.org/10.1016/j.isci.2022.104580
chicago: Bartalska, Katarina, Verena Hübschmann, Medina Korkut, Ryan J Cubero, Alessandro
Venturino, Karl Rössler, Thomas Czech, and Sandra Siegert. “A Systematic Characterization
of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” IScience.
Elsevier, 2022. https://doi.org/10.1016/j.isci.2022.104580.
ieee: K. Bartalska et al., “A systematic characterization of microglia-like
cell occurrence during retinal organoid differentiation,” iScience, vol.
25, no. 7. Elsevier, 2022.
ista: Bartalska K, Hübschmann V, Korkut M, Cubero RJ, Venturino A, Rössler K, Czech
T, Siegert S. 2022. A systematic characterization of microglia-like cell occurrence
during retinal organoid differentiation. iScience. 25(7), 104580.
mla: Bartalska, Katarina, et al. “A Systematic Characterization of Microglia-like
Cell Occurrence during Retinal Organoid Differentiation.” IScience, vol.
25, no. 7, 104580, Elsevier, 2022, doi:10.1016/j.isci.2022.104580.
short: K. Bartalska, V. Hübschmann, M. Korkut, R.J. Cubero, A. Venturino, K. Rössler,
T. Czech, S. Siegert, IScience 25 (2022).
date_created: 2022-07-03T22:01:33Z
date_published: 2022-07-15T00:00:00Z
date_updated: 2023-11-02T12:21:33Z
day: '15'
ddc:
- '610'
department:
- _id: SaSi
doi: 10.1016/j.isci.2022.104580
ec_funded: 1
external_id:
isi:
- '000830428500005'
file:
- access_level: open_access
checksum: a470b74e1b3796c710189c81a4cd4329
content_type: application/pdf
creator: cchlebak
date_created: 2022-07-04T08:19:25Z
date_updated: 2022-07-04T08:19:25Z
file_id: '11480'
file_name: 2022_iScience_Bartalska.pdf
file_size: 19400048
relation: main_file
success: 1
file_date_updated: 2022-07-04T08:19:25Z
has_accepted_license: '1'
intvolume: ' 25'
isi: 1
issue: '7'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
- _id: B67AFEDC-15C9-11EA-A837-991A96BB2854
name: IST Austria Open Access Fund
- _id: 9B99D380-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-017
name: How human microglia shape developing neurons during health and inflammation
publication: iScience
publication_identifier:
eissn:
- 2589-0042
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '12117'
relation: other
status: public
scopus_import: '1'
status: public
title: A systematic characterization of microglia-like cell occurrence during retinal
organoid differentiation
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 25
year: '2022'
...
---
_id: '11734'
abstract:
- lang: eng
text: Mineral nutrition is one of the key environmental factors determining plant
development and growth. Nitrate is the major form of macronutrient nitrogen that
plants take up from the soil. Fluctuating availability or deficiency of this element
severely limits plant growth and negatively affects crop production in the agricultural
system. To cope with the heterogeneity of nitrate distribution in soil, plants
evolved a complex regulatory mechanism that allows rapid adjustment of physiological
and developmental processes to the status of this nutrient. The root, as a major
exploitation organ that controls the uptake of nitrate to the plant body, acts
as a regulatory hub that, according to nitrate availability, coordinates the growth
and development of other plant organs. Here, we identified a regulatory framework,
where cytokinin response factors (CRFs) play a central role as a molecular readout
of the nitrate status in roots to guide shoot adaptive developmental response.
We show that nitrate-driven activation of NLP7, a master regulator of nitrate
response in plants, fine tunes biosynthesis of cytokinin in roots and its translocation
to shoots where it enhances expression of CRFs. CRFs, through direct transcriptional
regulation of PIN auxin transporters, promote the flow of auxin and thereby stimulate
the development of shoot organs.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: "We acknowledge Hana Semeradova, Juan Carlos Montesinos, Nicola Cavallari,
Marc¸al Gallem\x03ı, Kaori Tabata, Andrej Hurn\x03y, and Sascha Waidmann for sharing
materials; and Marina Borges Osorio for critical reading of the manuscript. Work
in the E. Benkova laboratory was supported by the Austrian Science Fund (FWF01_I1774S)
to K.O., R.A., and E. Benkova. We acknowledge the Bioimaging Facility and Life Science
Facilities of the Institute of Science\r\nand Technology Austria. We give sincere
thanks to Hana Martınkova and Petra Amakorova for their help with cytokinin analyses.
This work was funded by the Czech Science Foundation (Project No. 19-00973S)."
article_number: e2122460119
article_processing_charge: No
article_type: original
author:
- first_name: Rashed
full_name: Abualia, Rashed
id: 4827E134-F248-11E8-B48F-1D18A9856A87
last_name: Abualia
orcid: 0000-0002-9357-9415
- first_name: Krisztina
full_name: Ötvös, Krisztina
id: 29B901B0-F248-11E8-B48F-1D18A9856A87
last_name: Ötvös
orcid: 0000-0002-5503-4983
- first_name: Ondřej
full_name: Novák, Ondřej
last_name: Novák
- first_name: Eleonore
full_name: Bouguyon, Eleonore
last_name: Bouguyon
- first_name: Kevin
full_name: Domanegg, Kevin
id: a24c7829-16e8-11ed-8527-c4d36ffb7539
last_name: Domanegg
orcid: 0000-0002-1215-4264
- first_name: Anne
full_name: Krapp, Anne
last_name: Krapp
- first_name: Philip
full_name: Nacry, Philip
last_name: Nacry
- first_name: Alain
full_name: Gojon, Alain
last_name: Gojon
- first_name: Benoit
full_name: Lacombe, Benoit
last_name: Lacombe
- first_name: Eva
full_name: Benková, Eva
id: 38F4F166-F248-11E8-B48F-1D18A9856A87
last_name: Benková
orcid: 0000-0002-8510-9739
citation:
ama: Abualia R, Ötvös K, Novák O, et al. Molecular framework integrating nitrate
sensing in root and auxin-guided shoot adaptive responses. Proceedings of the
National Academy of Sciences of the United States of America. 2022;119(31).
doi:10.1073/pnas.2122460119
apa: Abualia, R., Ötvös, K., Novák, O., Bouguyon, E., Domanegg, K., Krapp, A., …
Benková, E. (2022). Molecular framework integrating nitrate sensing in root and
auxin-guided shoot adaptive responses. Proceedings of the National Academy
of Sciences of the United States of America. Proceedings of the National Academy
of Sciences. https://doi.org/10.1073/pnas.2122460119
chicago: Abualia, Rashed, Krisztina Ötvös, Ondřej Novák, Eleonore Bouguyon, Kevin
Domanegg, Anne Krapp, Philip Nacry, Alain Gojon, Benoit Lacombe, and Eva Benková.
“Molecular Framework Integrating Nitrate Sensing in Root and Auxin-Guided Shoot
Adaptive Responses.” Proceedings of the National Academy of Sciences of the
United States of America. Proceedings of the National Academy of Sciences,
2022. https://doi.org/10.1073/pnas.2122460119.
ieee: R. Abualia et al., “Molecular framework integrating nitrate sensing
in root and auxin-guided shoot adaptive responses,” Proceedings of the National
Academy of Sciences of the United States of America, vol. 119, no. 31. Proceedings
of the National Academy of Sciences, 2022.
ista: Abualia R, Ötvös K, Novák O, Bouguyon E, Domanegg K, Krapp A, Nacry P, Gojon
A, Lacombe B, Benková E. 2022. Molecular framework integrating nitrate sensing
in root and auxin-guided shoot adaptive responses. Proceedings of the National
Academy of Sciences of the United States of America. 119(31), e2122460119.
mla: Abualia, Rashed, et al. “Molecular Framework Integrating Nitrate Sensing in
Root and Auxin-Guided Shoot Adaptive Responses.” Proceedings of the National
Academy of Sciences of the United States of America, vol. 119, no. 31, e2122460119,
Proceedings of the National Academy of Sciences, 2022, doi:10.1073/pnas.2122460119.
short: R. Abualia, K. Ötvös, O. Novák, E. Bouguyon, K. Domanegg, A. Krapp, P. Nacry,
A. Gojon, B. Lacombe, E. Benková, Proceedings of the National Academy of Sciences
of the United States of America 119 (2022).
date_created: 2022-08-07T22:01:57Z
date_published: 2022-07-25T00:00:00Z
date_updated: 2023-08-03T12:39:29Z
day: '25'
ddc:
- '570'
department:
- _id: EvBe
doi: 10.1073/pnas.2122460119
external_id:
isi:
- '000881496900007'
pmid:
- '35878040'
file:
- access_level: open_access
checksum: 6e97dedc281247fc3fe238a209f14af0
content_type: application/pdf
creator: dernst
date_created: 2022-08-08T07:09:58Z
date_updated: 2022-08-08T07:09:58Z
file_id: '11744'
file_name: 2022_PNAS_Abualia.pdf
file_size: 3092330
relation: main_file
success: 1
file_date_updated: 2022-08-08T07:09:58Z
has_accepted_license: '1'
intvolume: ' 119'
isi: 1
issue: '31'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2542D156-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I 1774-B16
name: Hormone cross-talk drives nutrient dependent plant development
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- 1091-6490
publication_status: published
publisher: Proceedings of the National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Molecular framework integrating nitrate sensing in root and auxin-guided shoot
adaptive responses
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 119
year: '2022'
...
---
_id: '11879'
abstract:
- lang: eng
text: "As the overall global mean surface temperature is increasing due to climate
change, plant\r\nadaptation to those stressful conditions is of utmost importance
for their survival. Plants are\r\nsessile organisms, thus to compensate for their
lack of mobility, they evolved a variety of\r\nmechanisms enabling them to flexibly
adjust their physiological, growth and developmental\r\nprocesses to fluctuating
temperatures and to survive in harsh environments. While these unique\r\nadaptation
abilities provide an important evolutionary advantage, overall modulation of plant\r\ngrowth
and developmental program due to non-optimal temperature negatively affects biomass\r\nproduction,
crop productivity or sensitivity to pathogens. Thus, understanding molecular\r\nprocesses
underlying plant adaptation to increased temperature can provide important\r\nresources
for breeding strategies to ensure sufficient agricultural food production.\r\nAn
increase in ambient temperature by a few degrees leads to profound changes in
organ growth\r\nincluding enhanced hypocotyl elongation, expansion of petioles,
hyponastic growth of leaves and\r\ncotyledons, collectively named thermomorphogenesis
(Casal & Balasubramanian, 2019). Auxin,\r\none of the best-studied growth hormones,
plays an essential role in this process by direct\r\nactivation of transcriptional
and non-transcriptional processes resulting in elongation growth\r\n(Majda & Robert,
2018).To modulate hypocotyl growth in response to high ambient temperature\r\n(hAT),
auxin needs to be redistributed accordingly. PINs, auxin efflux transporters,
are key\r\ncomponents of the polar auxin transport (PAT) machinery, which controls
the amount and\r\ndirection of auxin translocated in the plant tissues and organs(Adamowski
& Friml, 2015). Hence,\r\nPIN-mediated transport is tightly linked with thermo-morphogenesis,
and interference with PAT\r\nthrough either chemical or genetic means dramatically
affecting the adaptive responses to hAT.\r\nIntriguingly, despite the key role
of PIN mediated transport in growth response to hAT, whether\r\nand how PINs at
the level of expression adapt to fluctuation in temperature is scarcely\r\nunderstood.\r\nWith
genetic, molecular and advanced bio-imaging approaches, we demonstrate the role
of PIN\r\nauxin transporters in the regulation of hypocotyl growth in response
to hAT. We show that via\r\nadjustment of PIN3, PIN4 and PIN7 expression in cotyledons
and hypocotyls, auxin distribution is modulated thereby determining elongation
pattern of epidermal cells at hAT. Furthermore, we\r\nidentified three Zinc-Finger
(ZF) transcription factors as novel molecular components of the\r\nthermo-regulatory
network, which through negative regulation of PIN transcription adjust the\r\ntransport
of auxin at hAT. Our results suggest that the ZF-PIN module might be a part of
the\r\nnegative feedback loop attenuating the activity of the thermo-sensing pathway
to restrain\r\nexaggerated growth and developmental responses to hAT."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: SSU
acknowledgement: I would like to acknowledge ISTA and all the people from the Scientific
Service Units and at ISTA, in particular Dorota Jaworska for excellent technical
and scientific support as well as ÖAW for funding my research for over 3 years (DOC
ÖAW Fellowship PR1022OEAW02).
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Christina
full_name: Artner, Christina
id: 45DF286A-F248-11E8-B48F-1D18A9856A87
last_name: Artner
citation:
ama: Artner C. Modulation of auxin transport via ZF proteins adjust plant response
to high ambient temperature. 2022. doi:10.15479/at:ista:11879
apa: Artner, C. (2022). Modulation of auxin transport via ZF proteins adjust
plant response to high ambient temperature. Institute of Science and Technology
Austria. https://doi.org/10.15479/at:ista:11879
chicago: Artner, Christina. “Modulation of Auxin Transport via ZF Proteins Adjust
Plant Response to High Ambient Temperature.” Institute of Science and Technology
Austria, 2022. https://doi.org/10.15479/at:ista:11879.
ieee: C. Artner, “Modulation of auxin transport via ZF proteins adjust plant response
to high ambient temperature,” Institute of Science and Technology Austria, 2022.
ista: Artner C. 2022. Modulation of auxin transport via ZF proteins adjust plant
response to high ambient temperature. Institute of Science and Technology Austria.
mla: Artner, Christina. Modulation of Auxin Transport via ZF Proteins Adjust
Plant Response to High Ambient Temperature. Institute of Science and Technology
Austria, 2022, doi:10.15479/at:ista:11879.
short: C. Artner, Modulation of Auxin Transport via ZF Proteins Adjust Plant Response
to High Ambient Temperature, Institute of Science and Technology Austria, 2022.
date_created: 2022-08-17T07:58:53Z
date_published: 2022-08-17T00:00:00Z
date_updated: 2023-09-09T22:30:04Z
day: '17'
ddc:
- '580'
degree_awarded: PhD
department:
- _id: GradSch
- _id: EvBe
doi: 10.15479/at:ista:11879
file:
- access_level: open_access
checksum: a2c2fdc28002538840490bfa6a08b2cb
content_type: application/pdf
creator: cartner
date_created: 2022-08-17T12:08:49Z
date_updated: 2023-09-09T22:30:03Z
embargo: 2023-09-08
file_id: '11907'
file_name: ChristinaArtner_PhD_Thesis_2022.pdf
file_size: 11113608
relation: main_file
- access_level: closed
checksum: 66b461c074b815fbe63481b3f46a9f43
content_type: application/octet-stream
creator: cartner
date_created: 2022-08-17T12:08:59Z
date_updated: 2023-09-09T22:30:03Z
embargo_to: open_access
file_id: '11908'
file_name: ChristinaArtner_PhD_Thesis_2022.7z
file_size: 19097730
relation: source_file
file_date_updated: 2023-09-09T22:30:03Z
has_accepted_license: '1'
keyword:
- high ambient temperature
- auxin
- PINs
- Zinc-Finger proteins
- thermomorphogenesis
- stress
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '128'
project:
- _id: 2685A872-B435-11E9-9278-68D0E5697425
name: Hormonal regulation of plant adaptive responses to environmental signals
publication_identifier:
isbn:
- 978-3-99078-022-0
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Eva
full_name: Benková, Eva
id: 38F4F166-F248-11E8-B48F-1D18A9856A87
last_name: Benková
orcid: 0000-0002-8510-9739
title: Modulation of auxin transport via ZF proteins adjust plant response to high
ambient temperature
type: dissertation
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11945'
abstract:
- lang: eng
text: "G protein-coupled receptors (GPCRs) respond to specific ligands and regulate
multiple processes ranging from cell growth and immune responses to neuronal signal
transmission. However, ligands for many GPCRs remain unknown, suffer from off-target
effects or have poor bioavailability. Additional challenges exist to dissect cell-type
specific responses when the same GPCR is expressed on several cell types within
the body. Here, we overcome these limitations by engineering DREADD-based GPCR
chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic
a GPCR-of-interest in a desired cell type.\r\nWe validated our approach with β2-adrenergic
receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable
responses on second messenger and kinase activity, post-translational modifications,
and protein-protein interactions. Since β2AR is also enriched in microglia, which
can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR
in primary microglia and successfully recapitulate β2AR-mediated filopodia formation
through CNO stimulation. To dissect the role of selected GPCRs during microglial
inflammation, we additionally generated DREADD-based chimeras for microglia-enriched
GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65
both modulated the inflammatory response with a similar profile as endogenously
expressed β2AR, while DREADD-GPR109A showed no impact.\r\nOur DREADD-based approach
provides the means to obtain mechanistic and functional insights into GPCR signaling
on a cell-type specific level."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
citation:
ama: Schulz R. Chimeric G protein-coupled receptors mimic distinct signaling pathways
and modulate microglia function. 2022. doi:10.15479/at:ista:11945
apa: Schulz, R. (2022). Chimeric G protein-coupled receptors mimic distinct signaling
pathways and modulate microglia function. Institute of Science and Technology
Austria. https://doi.org/10.15479/at:ista:11945
chicago: Schulz, Rouven. “Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
Pathways and Modulate Microglia Function.” Institute of Science and Technology
Austria, 2022. https://doi.org/10.15479/at:ista:11945.
ieee: R. Schulz, “Chimeric G protein-coupled receptors mimic distinct signaling
pathways and modulate microglia function,” Institute of Science and Technology
Austria, 2022.
ista: Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling
pathways and modulate microglia function. Institute of Science and Technology
Austria.
mla: Schulz, Rouven. Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
Pathways and Modulate Microglia Function. Institute of Science and Technology
Austria, 2022, doi:10.15479/at:ista:11945.
short: R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
Pathways and Modulate Microglia Function, Institute of Science and Technology
Austria, 2022.
date_created: 2022-08-23T11:33:11Z
date_published: 2022-08-23T00:00:00Z
date_updated: 2023-08-03T13:02:26Z
day: '23'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SaSi
doi: 10.15479/at:ista:11945
file:
- access_level: open_access
checksum: 61b1b666a210ff7cdd0e95ea75207a13
content_type: application/pdf
creator: rschulz
date_created: 2022-08-25T08:59:57Z
date_updated: 2022-08-25T08:59:57Z
file_id: '11970'
file_name: Thesis_Rouven_Schulz_2022_final.pdf
file_size: 28079331
relation: main_file
success: 1
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checksum: 2b8f95ea1c134dbdb927b41b1dbeeeb5
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: rschulz
date_created: 2022-08-25T09:00:11Z
date_updated: 2022-08-25T09:33:31Z
file_id: '11971'
file_name: Thesis_Rouven_Schulz_2022_final.docx
file_size: 27226963
relation: source_file
file_date_updated: 2022-08-25T09:33:31Z
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '133'
project:
- _id: 267F75D8-B435-11E9-9278-68D0E5697425
name: Modulating microglia through G protein-coupled receptor (GPCR) signaling
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '11995'
relation: dissertation_contains
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: Chimeric G protein-coupled receptors mimic distinct signaling pathways and
modulate microglia 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: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '11995'
abstract:
- lang: eng
text: G protein-coupled receptors (GPCRs) regulate processes ranging from immune
responses to neuronal signaling. However, ligands for many GPCRs remain unknown,
suffer from off-target effects or have poor bioavailability. Additionally, dissecting
cell type-specific responses is challenging when the same GPCR is expressed on
different cells within a tissue. Here, we overcome these limitations by engineering
DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest.
We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second
messenger and kinase activity, post-translational modifications, and protein-protein
interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation
in microglia, an immune cell capable of driving central nervous system inflammation.
When dissecting microglial inflammation, we included two additional DREADD-based
chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65
modulate the inflammatory response with high similarity to endogenous β2AR, while
DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation
of cell type-dependent pathways without known endogenous ligands.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
acknowledgement: The authors thank the Scientific Service Units at ISTA, in particular
the Molecular Biology Service of the Lab Support Facility, Imaging & Optics Facility,
and the Preclinical Facility, and the Novarino group, Harald Janoviak, and Marco
Benevento for sharing reagents and expertise. This research was supported by a DOC
Fellowship (24979) awarded to R.S. by the Austrian Academy of Sciences.
article_number: '4728'
article_processing_charge: No
article_type: original
author:
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
- 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: 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: Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. Chimeric GPCRs mimic
distinct signaling pathways and modulate microglia responses. Nature Communications.
2022;13. doi:10.1038/s41467-022-32390-1
apa: Schulz, R., Korkut, M., Venturino, A., Colombo, G., & Siegert, S. (2022).
Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses.
Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32390-1
chicago: Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and
Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate
Microglia Responses.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32390-1.
ieee: R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric
GPCRs mimic distinct signaling pathways and modulate microglia responses,” Nature
Communications, vol. 13. Springer Nature, 2022.
ista: Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. 2022. Chimeric GPCRs
mimic distinct signaling pathways and modulate microglia responses. Nature Communications.
13, 4728.
mla: Schulz, Rouven, et al. “Chimeric GPCRs Mimic Distinct Signaling Pathways and
Modulate Microglia Responses.” Nature Communications, vol. 13, 4728, Springer
Nature, 2022, doi:10.1038/s41467-022-32390-1.
short: R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications
13 (2022).
date_created: 2022-08-28T22:01:59Z
date_published: 2022-08-15T00:00:00Z
date_updated: 2024-02-21T12:34:51Z
day: '15'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41467-022-32390-1
external_id:
isi:
- '000840984400032'
pmid:
- '35970889'
file:
- access_level: open_access
checksum: 191d9db0266e14a28d3a56dc7f65da84
content_type: application/pdf
creator: cchlebak
date_created: 2022-08-29T06:44:30Z
date_updated: 2022-08-29T06:44:30Z
file_id: '12002'
file_name: 2022_NatComm_Schulz.pdf
file_size: 7317396
relation: main_file
success: 1
file_date_updated: 2022-08-29T06:44:30Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 267F75D8-B435-11E9-9278-68D0E5697425
name: Modulating microglia through G protein-coupled receptor (GPCR) signaling
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
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/dreaddful-mimicry/
record:
- id: '11945'
relation: part_of_dissertation
status: public
- id: '11542'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2022'
...
---
_id: '12138'
abstract:
- lang: eng
text: 'Complex I is the first enzyme in the respiratory chain, which is responsible
for energy production in mitochondria and bacteria1. Complex I couples the transfer
of two electrons from NADH to quinone and the translocation of four protons across
the membrane2, but the coupling mechanism remains contentious. Here we present
cryo-electron microscopy structures of Escherichia coli complex I (EcCI) in different
redox states, including catalytic turnover. EcCI exists mostly in the open state,
in which the quinone cavity is exposed to the cytosol, allowing access for water
molecules, which enable quinone movements. Unlike the mammalian paralogues3, EcCI
can convert to the closed state only during turnover, showing that closed and
open states are genuine turnover intermediates. The open-to-closed transition
results in the tightly engulfed quinone cavity being connected to the central
axis of the membrane arm, a source of substrate protons. Consistently, the proportion
of the closed state increases with increasing pH. We propose a detailed but straightforward
and robust mechanism comprising a ‘domino effect’ series of proton transfers and
electrostatic interactions: the forward wave (‘dominoes stacking’) primes the
pump, and the reverse wave (‘dominoes falling’) results in the ejection of all
pumped protons from the distal subunit NuoL. This mechanism explains why protons
exit exclusively from the NuoL subunit and is supported by our mutagenesis data.
We contend that this is a universal coupling mechanism of complex I and related
enzymes.'
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
- _id: ScienComp
acknowledgement: This research was supported by the Scientific Service Units (SSU)
of IST Austria through resources provided by the Electron Microscopy Facility (EMF),
the Life Science Facility (LSF) and the IST high-performance computing cluster.
We thank V.-V. Hodirnau from IST Austria EMF, M. Babiak from CEITEC for assistance
with collecting cryo-EM data and A. Charnagalov for the assistance with protein
purification. V.K. was a recipient of a DOC Fellowship of the Austrian Academy of
Sciences at the Institute of Science and Technology, Austria. V.K. and O.P. are
funded by the ERC Advanced Grant 101020697 RESPICHAIN to L.S. This work was also
supported by the Medical Research Council (UK).
article_processing_charge: No
article_type: original
author:
- first_name: Vladyslav
full_name: Kravchuk, Vladyslav
id: 4D62F2A6-F248-11E8-B48F-1D18A9856A87
last_name: Kravchuk
- first_name: Olga
full_name: Petrova, Olga
id: 5D8C9660-5D49-11EA-8188-567B3DDC885E
last_name: Petrova
- first_name: Domen
full_name: Kampjut, Domen
id: 37233050-F248-11E8-B48F-1D18A9856A87
last_name: Kampjut
- first_name: Anna
full_name: Wojciechowska-Bason, Anna
last_name: Wojciechowska-Bason
- first_name: Zara
full_name: Breese, Zara
last_name: Breese
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Kravchuk V, Petrova O, Kampjut D, Wojciechowska-Bason A, Breese Z, Sazanov
LA. A universal coupling mechanism of respiratory complex I. Nature. 2022;609(7928):808-814.
doi:10.1038/s41586-022-05199-7
apa: Kravchuk, V., Petrova, O., Kampjut, D., Wojciechowska-Bason, A., Breese, Z.,
& Sazanov, L. A. (2022). A universal coupling mechanism of respiratory complex
I. Nature. Springer Nature. https://doi.org/10.1038/s41586-022-05199-7
chicago: Kravchuk, Vladyslav, Olga Petrova, Domen Kampjut, Anna Wojciechowska-Bason,
Zara Breese, and Leonid A Sazanov. “A Universal Coupling Mechanism of Respiratory
Complex I.” Nature. Springer Nature, 2022. https://doi.org/10.1038/s41586-022-05199-7.
ieee: V. Kravchuk, O. Petrova, D. Kampjut, A. Wojciechowska-Bason, Z. Breese, and
L. A. Sazanov, “A universal coupling mechanism of respiratory complex I,” Nature,
vol. 609, no. 7928. Springer Nature, pp. 808–814, 2022.
ista: Kravchuk V, Petrova O, Kampjut D, Wojciechowska-Bason A, Breese Z, Sazanov
LA. 2022. A universal coupling mechanism of respiratory complex I. Nature. 609(7928),
808–814.
mla: Kravchuk, Vladyslav, et al. “A Universal Coupling Mechanism of Respiratory
Complex I.” Nature, vol. 609, no. 7928, Springer Nature, 2022, pp. 808–14,
doi:10.1038/s41586-022-05199-7.
short: V. Kravchuk, O. Petrova, D. Kampjut, A. Wojciechowska-Bason, Z. Breese, L.A.
Sazanov, Nature 609 (2022) 808–814.
date_created: 2023-01-12T12:04:33Z
date_published: 2022-09-22T00:00:00Z
date_updated: 2023-08-04T08:54:52Z
day: '22'
ddc:
- '572'
department:
- _id: LeSa
doi: 10.1038/s41586-022-05199-7
ec_funded: 1
external_id:
isi:
- '000854788200001'
pmid:
- '36104567'
file:
- access_level: open_access
checksum: d42a93e24f59e883ef0b5429832391d0
content_type: application/pdf
creator: lsazanov
date_created: 2023-05-30T17:05:31Z
date_updated: 2023-05-30T17:05:31Z
file_id: '13104'
file_name: EcCxI_manuscript_rev3_noSI_updated_withFigs_opt.pdf
file_size: 1425655
relation: main_file
success: 1
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checksum: 5422bc0a73b3daadafa262c7ea6deae3
content_type: application/pdf
creator: lsazanov
date_created: 2023-05-30T17:07:05Z
date_updated: 2023-05-30T17:07:05Z
file_id: '13105'
file_name: EcCxI_manuscript_rev3_SI_All_opt_upd.pdf
file_size: 9842513
relation: main_file
success: 1
file_date_updated: 2023-05-30T17:07:05Z
has_accepted_license: '1'
intvolume: ' 609'
isi: 1
issue: '7928'
keyword:
- Multidisciplinary
language:
- iso: eng
month: '09'
oa: 1
oa_version: Submitted Version
page: 808-814
pmid: 1
project:
- _id: 238A0A5A-32DE-11EA-91FC-C7463DDC885E
grant_number: '25541'
name: 'Structural characterization of E. coli complex I: an important mechanistic
model'
- _id: 627abdeb-2b32-11ec-9570-ec31a97243d3
call_identifier: H2020
grant_number: '101020697'
name: Structure and mechanism of respiratory chain molecular machines
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
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url: https://doi.org/10.1038/s41586-022-05457-8
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/proton-dominos-kick-off-life/
record:
- id: '12781'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: A universal coupling mechanism of respiratory complex I
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 609
year: '2022'
...