--- _id: '12370' abstract: - lang: eng text: 'Statistics of natural scenes are not uniform - their structure varies dramatically from ground to sky. It remains unknown whether these non-uniformities are reflected in the large-scale organization of the early visual system and what benefits such adaptations would confer. Here, by relying on the efficient coding hypothesis, we predict that changes in the structure of receptive fields across visual space increase the efficiency of sensory coding. We show experimentally that, in agreement with our predictions, receptive fields of retinal ganglion cells change their shape along the dorsoventral retinal axis, with a marked surround asymmetry at the visual horizon. Our work demonstrates that, according to principles of efficient coding, the panoramic structure of natural scenes is exploited by the retina across space and cell-types. ' acknowledged_ssus: - _id: ScienComp - _id: M-Shop - _id: Bio - _id: PreCl - _id: LifeSc article_processing_charge: No author: - first_name: Divyansh full_name: Gupta, Divyansh id: 2A485EBE-F248-11E8-B48F-1D18A9856A87 last_name: Gupta orcid: 0000-0001-7400-6665 - first_name: Anton L full_name: Sumser, Anton L id: 3320A096-F248-11E8-B48F-1D18A9856A87 last_name: Sumser orcid: 0000-0002-4792-1881 - first_name: Maximilian A full_name: Jösch, Maximilian A id: 2BD278E6-F248-11E8-B48F-1D18A9856A87 last_name: Jösch orcid: 0000-0002-3937-1330 citation: ama: 'Gupta D, Sumser AL, Jösch MA. Research Data for: Panoramic visual statistics shape retina-wide organization of receptive fields. 2023. doi:10.15479/AT:ISTA:12370' apa: 'Gupta, D., Sumser, A. L., & Jösch, M. A. (2023). Research Data for: Panoramic visual statistics shape retina-wide organization of receptive fields. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:12370' chicago: 'Gupta, Divyansh, Anton L Sumser, and Maximilian A Jösch. “Research Data for: Panoramic Visual Statistics Shape Retina-Wide Organization of Receptive Fields.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:12370.' ieee: 'D. Gupta, A. L. Sumser, and M. A. Jösch, “Research Data for: Panoramic visual statistics shape retina-wide organization of receptive fields.” Institute of Science and Technology Austria, 2023.' ista: 'Gupta D, Sumser AL, Jösch MA. 2023. Research Data for: Panoramic visual statistics shape retina-wide organization of receptive fields, Institute of Science and Technology Austria, 10.15479/AT:ISTA:12370.' mla: 'Gupta, Divyansh, et al. Research Data for: Panoramic Visual Statistics Shape Retina-Wide Organization of Receptive Fields. Institute of Science and Technology Austria, 2023, doi:10.15479/AT:ISTA:12370.' short: D. Gupta, A.L. Sumser, M.A. Jösch, (2023). contributor: - contributor_type: researcher first_name: Olga id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87 last_name: Symonova - contributor_type: researcher first_name: Wiktor F id: 358A453A-F248-11E8-B48F-1D18A9856A87 last_name: Mlynarski - contributor_type: researcher first_name: Jan id: f7f724c3-9d6f-11ed-9f44-e5c5f3a5bee2 last_name: Svaton corr_author: '1' date_created: 2023-01-25T12:45:18Z date_published: 2023-01-26T00:00:00Z date_updated: 2026-09-17T22:30:35Z day: '26' ddc: - '571' department: - _id: GradSch - _id: MaJö doi: 10.15479/AT:ISTA:12370 ec_funded: 1 file: - access_level: open_access checksum: 172cd1c315cbf063c122298396bc17a7 content_type: text/plain creator: dgupta date_created: 2023-01-26T10:51:34Z date_updated: 2023-01-26T10:51:34Z file_id: '12396' file_name: readme_exvivo.txt file_size: 1917 relation: main_file success: 1 - access_level: open_access checksum: d3cecda51cad86b1182195731c01a14f content_type: text/plain creator: dgupta date_created: 2023-01-26T10:50:50Z date_updated: 2023-01-26T10:50:50Z file_id: '12397' file_name: readme_invivo.txt file_size: 1585 relation: main_file success: 1 - 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access_level: open_access checksum: 9483686a44e69eadea428b705c33a9a2 content_type: application/octet-stream creator: dgupta date_created: 2023-01-25T16:23:02Z date_updated: 2023-01-25T16:23:02Z file_id: '12389' file_name: invivo_BL6-eyeGC8m-dC-5_220630_1518_Result.mat file_size: 1617777136 relation: main_file success: 1 file_date_updated: 2023-01-26T10:51:34Z fulldoi: https://doi.org/10.15479/AT:ISTA:12370 has_accepted_license: '1' license: https://creativecommons.org/licenses/by-nc-sa/4.0/ month: '01' oa: 1 oa_version: Published Version project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 626c45b5-2b32-11ec-9570-e509828c1ba6 grant_number: P34015 name: Efficient coding with biophysical realism - _id: 2634E9D2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '756502' name: Circuits of Visual Attention - _id: 266D407A-B435-11E9-9278-68D0E5697425 grant_number: LT000256 name: Neuronal networks of salience and spatial detection in the murine superior colliculus - _id: 264FEA02-B435-11E9-9278-68D0E5697425 grant_number: ALTF 1098-2017 name: Connecting sensory with motor processing in the superior colliculus publisher: Institute of Science and Technology Austria related_material: record: - id: '12349' relation: used_in_publication status: public - id: '18574' relation: used_in_publication status: public status: public title: 'Research Data for: Panoramic visual statistics shape retina-wide organization of receptive fields' tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- OA_place: publisher _id: '14510' abstract: - lang: eng text: "Clathrin-mediated endocytosis (CME) is vital for the regulation of plant growth and\r\ndevelopment by controlling plasma membrane protein composition and cargo uptake. CME\r\nrelies on the precise recruitment control of protein regulators for vesicle maturation and\r\nrelease. During the early stages of endocytosis, an area of flat membrane is remodelled by\r\nproteins to create a spherical vesicle against intracellular forces. After the Clathrin-coated\r\nvesicle (CCV) is fully formed, scission machinery releases it from the plasma membrane,\r\nand cargo proceeds for recycling or degradation through early endosomes / Trans Golgi\r\nnetwork. Protein machineries that mediate membrane bending and vesicle release in plants\r\nare unknown. However, studies show, that plant endocytosis is actin independent, thus\r\nindicating that plants utilize a unique mechanism to mediate membrane bending against highturgor pressure compared to other model systems. First, by using biochemical and advanced\r\nlive microscopy approaches we investigate the TPLATE complex, a plant-specific\r\nendocytosis protein complex. We found that TPLATE is peripherally associated with\r\nclathrin-coated vesicles and localises at the rim of endocytosis events. Next, our study of\r\nplant Dynamin-related protein 1C (DRP1C), which was hypothesised previously to play a\r\nrole in vesicle release, shows the recruitment of the protein already at the early stages of\r\nendocytosis. Moreover, DRP1C assembles into organised ring-like structures and is able to\r\ninduce membrane deformation and tubulation, suggesting its role also in membrane bending\r\nduring early CME. Based on the data from mammalian and yeast systems, plant DynaminRelated Proteins 2 and SH3P2 protein are strong candidates to be part of the plant vesicle\r\nscission machinery; however, their precise role in plant CME has not been yet elucidated.\r\nHere, we characterised DRP2s and SH3P2 roles in CME by combining high-resolution\r\nimaging of endocytic events in vivo and protein characterisation. Although DRP2s and\r\nSH3P2 arrive together during late CME and physically interact, genetic analysis using\r\n∆sh3p1,2,3 mutant and complementation with non-DRP2-interacting SH3P2 variants suggest\r\nthat SH3P2 does not directly recruit DRP2s to the site of endocytosis. Summarising our\r\nresearch, these observations provide new important insights into the mechanism of plant\r\nCME and show that, despite plants posses many homologues of mammalian and yeast CME\r\ncomponents, they do not necessarily act in the same manner. " acknowledged_ssus: - _id: EM-Fac - _id: Bio - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Nataliia full_name: Gnyliukh, Nataliia id: 390C1120-F248-11E8-B48F-1D18A9856A87 last_name: Gnyliukh orcid: 0000-0002-2198-0509 citation: ama: Gnyliukh N. Mechanism of clathrin-coated vesicle  formation during endocytosis in plants. 2023. doi:10.15479/at:ista:14510 apa: Gnyliukh, N. (2023). Mechanism of clathrin-coated vesicle  formation during endocytosis in plants. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14510 chicago: Gnyliukh, Nataliia. “Mechanism of Clathrin-Coated Vesicle  Formation during Endocytosis in Plants.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:14510. ieee: N. Gnyliukh, “Mechanism of clathrin-coated vesicle  formation during endocytosis in plants,” Institute of Science and Technology Austria, 2023. ista: Gnyliukh N. 2023. Mechanism of clathrin-coated vesicle  formation during endocytosis in plants. Institute of Science and Technology Austria. mla: Gnyliukh, Nataliia. Mechanism of Clathrin-Coated Vesicle  Formation during Endocytosis in Plants. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:14510. short: N. Gnyliukh, Mechanism of Clathrin-Coated Vesicle  Formation during Endocytosis in Plants, Institute of Science and Technology Austria, 2023. corr_author: '1' date_created: 2023-11-10T09:10:06Z date_published: 2023-11-10T00:00:00Z date_updated: 2026-09-17T22:30:56Z day: '10' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: JiFr - _id: MaLo doi: 10.15479/at:ista:14510 ec_funded: 1 file: - access_level: closed checksum: 3d5e680bfc61f98e308c434f45cc9bd6 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: ngnyliuk date_created: 2023-11-20T09:18:51Z date_updated: 2024-11-23T23:30:38Z embargo_to: open_access file_id: '14567' file_name: Thesis_Gnyliukh_final_08_11_23.docx file_size: 20824903 relation: source_file - access_level: open_access checksum: bfc96d47fc4e7e857dd71656097214a4 content_type: application/pdf creator: ngnyliuk date_created: 2023-11-20T09:23:11Z date_updated: 2024-11-23T23:30:38Z embargo: 2024-11-23 file_id: '14568' file_name: Thesis_Gnyliukh_final_20_11_23.pdf file_size: 24871844 relation: main_file file_date_updated: 2024-11-23T23:30:38Z fulldoi: https://doi.org/10.15479/at:ista:14510 has_accepted_license: '1' keyword: - Clathrin-Mediated Endocytosis - vesicle scission - Dynamin-Related Protein 2 - SH3P2 - TPLATE complex - Total internal reflection fluorescence microscopy - Arabidopsis thaliana language: - iso: eng month: '11' oa: 1 oa_version: Published Version page: '180' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication_identifier: isbn: - 978-3-99078-037-4 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '14591' relation: part_of_dissertation status: public - id: '9887' relation: part_of_dissertation status: public - id: '8139' relation: part_of_dissertation status: public status: public supervisor: - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 - first_name: Martin full_name: Loose, Martin id: 462D4284-F248-11E8-B48F-1D18A9856A87 last_name: Loose orcid: 0000-0001-7309-9724 title: Mechanism of clathrin-coated vesicle formation during endocytosis in plants tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: repository _id: '14591' abstract: - lang: eng text: Clathrin-mediated endocytosis (CME) is vital for the regulation of plant growth and development by controlling plasma membrane protein composition and cargo uptake. CME relies on the precise recruitment of regulators for vesicle maturation and release. Homologues of components of mammalian vesicle scission are strong candidates to be part of the scissin machinery in plants, but the precise roles of these proteins in this process is not fully understood. Here, we characterised the roles of Plant Dynamin-Related Proteins 2 (DRP2s) and SH3-domain containing protein 2 (SH3P2), the plant homologue to Dynamins’ recruiters, like Endophilin and Amphiphysin, in the CME by combining high-resolution imaging of endocytic events in vivo and characterisation of the purified proteins in vitro. Although DRP2s and SH3P2 arrive similarly late during CME and physically interact, genetic analysis of the Dsh3p1,2,3 triple-mutant and complementation assays with non-SH3P2-interacting DRP2 variants suggests that SH3P2 does not directly recruit DRP2s to the site of endocytosis. These observations imply that despite the presence of many well-conserved endocytic components, plants have acquired a distinct mechanism for CME. One Sentence Summary In contrast to predictions based on mammalian systems, plant Dynamin-related proteins 2 are recruited to the site of Clathrin-mediated endocytosis independently of BAR-SH3 proteins. acknowledged_ssus: - _id: EM-Fac - _id: LifeSc - _id: Bio article_processing_charge: No author: - first_name: Nataliia full_name: Gnyliukh, Nataliia id: 390C1120-F248-11E8-B48F-1D18A9856A87 last_name: Gnyliukh orcid: 0000-0002-2198-0509 - first_name: Alexander J full_name: Johnson, Alexander J id: 46A62C3A-F248-11E8-B48F-1D18A9856A87 last_name: Johnson orcid: 0000-0002-2739-8843 - first_name: Marie-Kristin full_name: Nagel, Marie-Kristin last_name: Nagel - first_name: Aline full_name: Monzer, Aline id: 2DB5D88C-D7B3-11E9-B8FD-7907E6697425 last_name: Monzer - first_name: Annamaria full_name: Hlavata, Annamaria id: 36062FEC-F248-11E8-B48F-1D18A9856A87 last_name: Hlavata - first_name: Erika full_name: Isono, Erika last_name: Isono - first_name: Martin full_name: Loose, Martin id: 462D4284-F248-11E8-B48F-1D18A9856A87 last_name: Loose orcid: 0000-0001-7309-9724 - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 citation: ama: Gnyliukh N, Johnson AJ, Nagel M-K, et al. Role of dynamin-related proteins 2 and SH3P2 in clathrin-mediated endocytosis in plants. bioRxiv. doi:10.1101/2023.10.09.561523 apa: Gnyliukh, N., Johnson, A. J., Nagel, M.-K., Monzer, A., Hlavata, A., Isono, E., … Friml, J. (n.d.). Role of dynamin-related proteins 2 and SH3P2 in clathrin-mediated endocytosis in plants. bioRxiv. https://doi.org/10.1101/2023.10.09.561523 chicago: Gnyliukh, Nataliia, Alexander J Johnson, Marie-Kristin Nagel, Aline Monzer, Annamaria Hlavata, Erika Isono, Martin Loose, and Jiří Friml. “Role of Dynamin-Related Proteins 2 and SH3P2 in Clathrin-Mediated Endocytosis in Plants.” BioRxiv, n.d. https://doi.org/10.1101/2023.10.09.561523. ieee: N. Gnyliukh et al., “Role of dynamin-related proteins 2 and SH3P2 in clathrin-mediated endocytosis in plants,” bioRxiv. . ista: Gnyliukh N, Johnson AJ, Nagel M-K, Monzer A, Hlavata A, Isono E, Loose M, Friml J. Role of dynamin-related proteins 2 and SH3P2 in clathrin-mediated endocytosis in plants. bioRxiv, 10.1101/2023.10.09.561523. mla: Gnyliukh, Nataliia, et al. “Role of Dynamin-Related Proteins 2 and SH3P2 in Clathrin-Mediated Endocytosis in Plants.” BioRxiv, doi:10.1101/2023.10.09.561523. short: N. Gnyliukh, A.J. Johnson, M.-K. Nagel, A. Monzer, A. Hlavata, E. Isono, M. Loose, J. Friml, BioRxiv (n.d.). corr_author: '1' date_created: 2023-11-22T10:17:49Z date_published: 2023-10-10T00:00:00Z date_updated: 2026-09-17T22:30:55Z day: '10' department: - _id: JiFr - _id: MaLo - _id: CaBe doi: 10.1101/2023.10.09.561523 ec_funded: 1 fulldoi: https://doi.org/10.1101/2023.10.09.561523 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2023.10.09.561523 month: '10' oa: 1 oa_version: Preprint project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: bioRxiv publication_status: draft related_material: record: - id: '15330' relation: later_version status: public - id: '14510' relation: dissertation_contains status: public status: public title: Role of dynamin-related proteins 2 and SH3P2 in clathrin-mediated endocytosis in plants type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- OA_place: publisher _id: '12470' abstract: - lang: eng text: "The brain is an exceptionally sophisticated organ consisting of billions of cells and trillions of \r\nconnections that orchestrate our cognition and behavior. To decode its complex connectivity, it is \r\npivotal to disentangle its intricate architecture spanning from cm-sized circuits down to tens of \r\nnm-small synapses.\r\nTo achieve this goal, I developed CATS – Comprehensive Analysis of nervous Tissue across \r\nScales, a versatile toolbox for obtaining a holistic view of nervous tissue context with (super\x02resolution) fluorescence microscopy. CATS combines comprehensive labeling of the extracellular\r\nspace, that is compatible with chemical fixation, with information on molecular markers, super\x02resolved data acquisition and machine-learning based data analysis for segmentation and synapse \r\nidentification.\r\nI used CATS to analyze key features of nervous tissue connectivity, ranging from whole tissue \r\narchitecture, neuronal in- and output-fields, down to synapse morphology.\r\nFocusing on the hippocampal circuitry, I quantified synaptic transmission properties of mossy \r\nfiber boutons and analyzed the connectivity pattern of dentate gyrus granule cells with CA3 \r\npyramidal neurons. This shows that CATS is a viable tool to study hallmarks of neuronal \r\nconnectivity with light microscopy." acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: PreCl - _id: EM-Fac - _id: M-Shop - _id: ScienComp alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 citation: ama: Michalska JM. A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy. 2023. doi:10.15479/at:ista:12470 apa: Michalska, J. M. (2023). A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12470 chicago: Michalska, Julia M. “A Versatile Toolbox for the Comprehensive Analysis of Nervous Tissue Organization with Light Microscopy.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12470. ieee: J. M. Michalska, “A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy,” Institute of Science and Technology Austria, 2023. ista: Michalska JM. 2023. A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy. Institute of Science and Technology Austria. mla: Michalska, Julia M. A Versatile Toolbox for the Comprehensive Analysis of Nervous Tissue Organization with Light Microscopy. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12470. short: J.M. Michalska, A Versatile Toolbox for the Comprehensive Analysis of Nervous Tissue Organization with Light Microscopy, Institute of Science and Technology Austria, 2023. corr_author: '1' date_created: 2023-01-31T15:10:53Z date_published: 2023-01-09T00:00:00Z date_updated: 2026-07-06T12:50:45Z day: '09' ddc: - '610' degree_awarded: PhD department: - _id: GradSch - _id: JoDa doi: 10.15479/at:ista:12470 ec_funded: 1 file: - access_level: open_access checksum: 1a2306e5f59f52df598e7ecfadf921ac content_type: application/pdf creator: cchlebak date_created: 2023-01-31T15:11:42Z date_updated: 2023-07-27T22:30:54Z embargo: 2023-07-09 file_id: '12471' file_name: 20230109_PhD_thesis_JM_final.pdf file_size: 41771714 relation: main_file - access_level: closed checksum: 0bebbdee0773443959e1f6ab8caf281f content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cchlebak date_created: 2023-01-31T15:11:51Z date_updated: 2023-07-10T22:30:04Z embargo_to: open_access file_id: '12472' file_name: 20230109_PhD_thesis_JM_final.docx file_size: 66983464 relation: source_file file_date_updated: 2023-07-27T22:30:54Z fulldoi: https://doi.org/10.15479/at:ista:12470 has_accepted_license: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: '201' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 26AA4EF2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets publication_identifier: isbn: - 978-3-99078-026-8 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '11943' relation: part_of_dissertation status: public - id: '11950' relation: part_of_dissertation status: public status: public supervisor: - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 title: A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- _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 orcid: 0000-0001-6726-3890 - 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). corr_author: '1' date_created: 2022-03-06T23:01:52Z date_published: 2022-02-24T00:00:00Z date_updated: 2026-04-02T12:45:39Z 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 fulldoi: https://doi.org/10.7554/eLife.68040 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: - 2050-084X 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: ba8df636-2132-11f1-aed0-ed93e2281fdd volume: 11 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 orcid: 0000-0003-1756-6564 - 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). corr_author: '1' date_created: 2022-04-15T07:10:26Z date_published: 2022-06-01T00:00:00Z date_updated: 2025-04-15T08:24:50Z 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 fulldoi: https://doi.org/10.1016/j.jsb.2022.107852 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: '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 orcid: 0000-0002-7462-0048 - 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). corr_author: '1' date_created: 2022-04-26T15:04:50Z date_published: 2022-11-01T00:00:00Z date_updated: 2025-09-09T14:30:38Z day: '01' ddc: - '570' department: - _id: SiHi doi: 10.1126/sciadv.abq1263 ec_funded: 1 external_id: isi: - '000918406800019' pmid: - '36322669' 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 fulldoi: https://doi.org/10.1126/sciadv.abq1263 has_accepted_license: '1' intvolume: ' 8' isi: 1 issue: '44' language: - iso: eng month: '11' oa: 1 oa_version: Published Version pmid: 1 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: T01031 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 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: 2025-04-14T09:40:45Z 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 fulldoi: https://doi.org/10.1038/s41586-022-04633-0 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: '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). corr_author: '1' date_created: 2022-06-18T09:06:59Z date_published: 2022-05-05T00:00:00Z date_updated: 2026-04-07T13:25:01Z day: '05' ddc: - '570' department: - _id: GradSch - _id: FyKo doi: 10.7554/elife.75842 ec_funded: 1 external_id: isi: - '000799197200001' pmid: - '35510622' 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 fulldoi: https://doi.org/10.7554/elife.75842 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 pmid: 1 project: - _id: 26580278-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '771209' name: Characterizing the fitness landscape on population and global scales - _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' related_material: link: - relation: software url: https://github.com/aequorea238/Orthologous_GFP_Fitness_Peaks record: - id: '17850' relation: dissertation_contains status: public 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 11 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. 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. 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. 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, 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). corr_author: '1' date_created: 2022-08-07T22:01:57Z date_published: 2022-07-25T00:00:00Z date_updated: 2025-05-14T11:00:29Z 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 fulldoi: https://doi.org/10.1073/pnas.2122460119 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: 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 119 year: '2022' ... --- OA_place: publisher _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. corr_author: '1' date_created: 2022-08-23T11:33:11Z date_published: 2022-08-23T00:00:00Z date_updated: 2026-04-07T14:17:59Z 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 - access_level: closed 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 fulldoi: https://doi.org/10.15479/at:ista:11945 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: ba8df636-2132-11f1-aed0-ed93e2281fdd 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). corr_author: '1' date_created: 2022-08-28T22:01:59Z date_published: 2022-08-15T00:00:00Z date_updated: 2026-04-07T14:17:58Z 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 fulldoi: https://doi.org/10.1038/s41467-022-32390-1 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: '11542' relation: research_data status: public - id: '11945' relation: part_of_dissertation 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: '12144' abstract: - lang: eng text: The phytohormone auxin is the major coordinative signal in plant development1, mediating transcriptional reprogramming by a well-established canonical signalling pathway. TRANSPORT INHIBITOR RESPONSE 1 (TIR1)/AUXIN-SIGNALING F-BOX (AFB) auxin receptors are F-box subunits of ubiquitin ligase complexes. In response to auxin, they associate with Aux/IAA transcriptional repressors and target them for degradation via ubiquitination2,3. Here we identify adenylate cyclase (AC) activity as an additional function of TIR1/AFB receptors across land plants. Auxin, together with Aux/IAAs, stimulates cAMP production. Three separate mutations in the AC motif of the TIR1 C-terminal region, all of which abolish the AC activity, each render TIR1 ineffective in mediating gravitropism and sustained auxin-induced root growth inhibition, and also affect auxin-induced transcriptional regulation. These results highlight the importance of TIR1/AFB AC activity in canonical auxin signalling. They also identify a unique phytohormone receptor cassette combining F-box and AC motifs, and the role of cAMP as a second messenger in plants. acknowledged_ssus: - _id: LifeSc - _id: Bio acknowledgement: This research was supported by the Lab Support Facility (LSF) and the Imaging and Optics Facility (IOF) of IST Austria. We thank C. Gehring for suggestions and advice; and K. U. Torii and G. Stacey for seeds and plasmids. This project was funded by a European Research Council Advanced Grant (ETAP-742985). M.F.K. and R.N. acknowledge the support of the EU MSCA-IF project CrysPINs (792329). M.K. was supported by the project POWR.03.05.00-00-Z302/17 Universitas Copernicana Thoruniensis in Futuro–IDS “Academia Copernicana”. CIDG acknowledges support from UKRI under Future Leaders Fellowship grant number MR/T020652/1. article_processing_charge: No article_type: original author: - first_name: Linlin full_name: Qi, Linlin id: 44B04502-A9ED-11E9-B6FC-583AE6697425 last_name: Qi orcid: 0000-0001-5187-8401 - first_name: Mateusz full_name: Kwiatkowski, Mateusz last_name: Kwiatkowski - first_name: Huihuang full_name: Chen, Huihuang id: 83c96512-15b2-11ec-abd3-b7eede36184f last_name: Chen - first_name: Lukas full_name: Hörmayer, Lukas id: 2EEE7A2A-F248-11E8-B48F-1D18A9856A87 last_name: Hörmayer orcid: 0000-0001-8295-2926 - first_name: Scott A full_name: Sinclair, Scott A id: 2D99FE6A-F248-11E8-B48F-1D18A9856A87 last_name: Sinclair orcid: 0000-0002-4566-0593 - first_name: Minxia full_name: Zou, Minxia id: 5c243f41-03f3-11ec-841c-96faf48a7ef9 last_name: Zou - first_name: Charo I. full_name: del Genio, Charo I. last_name: del Genio - first_name: Martin F. full_name: Kubeš, Martin F. last_name: Kubeš - first_name: Richard full_name: Napier, Richard last_name: Napier - first_name: Krzysztof full_name: Jaworski, Krzysztof last_name: Jaworski - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 citation: ama: Qi L, Kwiatkowski M, Chen H, et al. Adenylate cyclase activity of TIR1/AFB auxin receptors in plants. Nature. 2022;611(7934):133-138. doi:10.1038/s41586-022-05369-7 apa: Qi, L., Kwiatkowski, M., Chen, H., Hörmayer, L., Sinclair, S. A., Zou, M., … Friml, J. (2022). Adenylate cyclase activity of TIR1/AFB auxin receptors in plants. Nature. Springer Nature. https://doi.org/10.1038/s41586-022-05369-7 chicago: Qi, Linlin, Mateusz Kwiatkowski, Huihuang Chen, Lukas Hörmayer, Scott A Sinclair, Minxia Zou, Charo I. del Genio, et al. “Adenylate Cyclase Activity of TIR1/AFB Auxin Receptors in Plants.” Nature. Springer Nature, 2022. https://doi.org/10.1038/s41586-022-05369-7. ieee: L. Qi et al., “Adenylate cyclase activity of TIR1/AFB auxin receptors in plants,” Nature, vol. 611, no. 7934. Springer Nature, pp. 133–138, 2022. ista: Qi L, Kwiatkowski M, Chen H, Hörmayer L, Sinclair SA, Zou M, del Genio CI, Kubeš MF, Napier R, Jaworski K, Friml J. 2022. Adenylate cyclase activity of TIR1/AFB auxin receptors in plants. Nature. 611(7934), 133–138. mla: Qi, Linlin, et al. “Adenylate Cyclase Activity of TIR1/AFB Auxin Receptors in Plants.” Nature, vol. 611, no. 7934, Springer Nature, 2022, pp. 133–38, doi:10.1038/s41586-022-05369-7. short: L. Qi, M. Kwiatkowski, H. Chen, L. Hörmayer, S.A. Sinclair, M. Zou, C.I. del Genio, M.F. Kubeš, R. Napier, K. Jaworski, J. Friml, Nature 611 (2022) 133–138. corr_author: '1' date_created: 2023-01-12T12:06:05Z date_published: 2022-11-03T00:00:00Z date_updated: 2025-04-14T07:45:02Z day: '03' department: - _id: JiFr doi: 10.1038/s41586-022-05369-7 ec_funded: 1 external_id: isi: - '000875061600013' pmid: - '36289340' fulldoi: https://doi.org/10.1038/s41586-022-05369-7 intvolume: ' 611' isi: 1 issue: '7934' language: - iso: eng main_file_link: - open_access: '1' url: http://wrap.warwick.ac.uk/168325/1/WRAP-denylate-cyclase-activity-TIR1-AFB-auxin-receptors-root-growth-22.pdf month: '11' oa: 1 oa_version: Submitted Version page: 133-138 pmid: 1 project: - _id: 261099A6-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742985' name: Tracing Evolution of Auxin Transport and Polarity in Plants 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: Adenylate cyclase activity of TIR1/AFB auxin receptors in plants type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 611 year: '2022' ... --- _id: '12174' abstract: - lang: eng text: "Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease.\r\nHere we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased patient to 22 years, oldest patient) clinical pictures included early lethal encephalopathies with rapidly progressive massive brain atrophy, severe developmental epileptic encephalopathies and static intellectual disability with epilepsy. The first clinical manifestation was early hypotonia, in 70%; 81% developed epilepsy, manifested as developmental epileptic encephalopathies in 58% of the cohort and with infantile spasms in 62%; 63% of developmental epileptic encephalopathies failed to achieve any developmental, communicative or motor skills. Less severe outcomes were observed in 23% of patients who, at a mean age of 10 years and 6 months, exhibited moderate intellectual disability, with independent walking and variable epilepsy. None of the patients developed communicative language. Microcephaly (38%) and amelogenesis imperfecta/enamel dysplasia (42%) were additional clinical features. Brain MRI demonstrated hypomyelination and generalized atrophy in 68%. Atrophy was progressive in all eight individuals undergoing repeated MRIs.\r\n \ Fibroblasts of two patients with developmental epileptic encephalopathies showed decreased LAMP1 expression, Lysotracker staining and increased organelle pH, consistent with lysosomal impairment and loss of V-ATPase function. Fibroblasts of two patients with milder disease, exhibited a different phenotype with increased Lysotracker staining, decreased organelle pH and no significant modification in LAMP1 expression. Quantification of substrates for lysosomal enzymes in cellular extracts from four patients revealed discrete accumulation. Transmission electron microscopy of fibroblasts of four patients with variable severity and of induced pluripotent stem cell-derived neurons from two patients with developmental epileptic encephalopathies showed electron-dense inclusions, lipid droplets, osmiophilic material and lamellated membrane structures resembling phospholipids. Quantitative assessment in induced pluripotent stem cell-derived neurons identified significantly smaller lysosomes.\r\nATP6V1A-related encephalopathy represents a new paradigm among lysosomal disorders. It results from a dysfunctional endo-lysosomal membrane protein causing altered pH homeostasis. Its pathophysiology implies intracellular accumulation of substrates whose composition remains unclear, and a combination of developmental brain abnormalities and neurodegenerative changes established during prenatal and early postanal development, whose severity is variably determined by specific pathogenic variants." acknowledged_ssus: - _id: EM-Fac - _id: LifeSc acknowledgement: "We thank all patients and family members for their participation in this study. We thank Melanie Pieraks and Eva Reinthaler (Neurolentech, Austria) for generating the human iPSC lines and\r\nfor performing quality checks. We thank Vanessa Zheden and Daniel Gütl for their excellent technical support in the specimen preparation for transmission electron microscopy and Flavia Leite for preparing the lentiviruses. The support from Electron Microscopy Facility and Molecular Biology Services at IST Austria is greatly acknowledged. We would like to thank Doctors Jane Hurst and Richard Scott for their help in retrieving the detailed clinical information of Patient 17. The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. See Supplementary Material for Undiagnosed Disease Network consortium details. Genetic information on Patient 23 was made available through access to the data and findings generated by the 100 000 Genomes\r\nProject; www.genomicsengland.co.uk (to K.L.). \r\nThis work was supported by the EU 7th Framework Programme (FP7) under the project DESIRE grant N602531 (to R.G.); the Regione Toscana under the Call for Health 2018 (grant\r\nDECODE-EE) (to R.G.); the ‘Brain Project’ by Fondazione Cassa di Risparmio di Firenze (to R.G.); IRCCS Ospedale Policlinico San Martino 5×1000 and Ricerca Corrente (to A.F. and F.B.). The European Reference Network (ERN) for rare and complex epilepsies (EpiCARE) provided financial support for meetings organization. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication\r\nare those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). This study makes use of DECIPHER (https://www.deciphergenomics.org), which is funded by Wellcome. K.K.-S. was supported by the ISTplus fellowship. " article_processing_charge: No article_type: original author: - first_name: Renzo full_name: Guerrini, Renzo last_name: Guerrini - first_name: Davide full_name: Mei, Davide last_name: Mei - first_name: Margit Katalin full_name: Szigeti, Margit Katalin id: 44F4BDC0-F248-11E8-B48F-1D18A9856A87 last_name: Szigeti orcid: 0000-0001-9500-8758 - first_name: Sara full_name: Pepe, Sara last_name: Pepe - first_name: Mary Kay full_name: Koenig, Mary Kay last_name: Koenig - first_name: Gretchen full_name: Von Allmen, Gretchen last_name: Von Allmen - first_name: Megan T full_name: Cho, Megan T last_name: Cho - first_name: Kimberly full_name: McDonald, Kimberly last_name: McDonald - first_name: Janice full_name: Baker, Janice last_name: Baker - first_name: Vikas full_name: Bhambhani, Vikas last_name: Bhambhani - first_name: Zöe full_name: Powis, Zöe last_name: Powis - first_name: Lance full_name: Rodan, Lance last_name: Rodan - first_name: Rima full_name: Nabbout, Rima last_name: Nabbout - first_name: Giulia full_name: Barcia, Giulia last_name: Barcia - first_name: Jill A full_name: Rosenfeld, Jill A last_name: Rosenfeld - first_name: Carlos A full_name: Bacino, Carlos A last_name: Bacino - first_name: Cyril full_name: Mignot, Cyril last_name: Mignot - first_name: Lillian H full_name: Power, Lillian H last_name: Power - first_name: Catharine J full_name: Harris, Catharine J last_name: Harris - first_name: Dragan full_name: Marjanovic, Dragan last_name: Marjanovic - first_name: Rikke S full_name: Møller, Rikke S last_name: Møller - first_name: Trine B full_name: Hammer, Trine B last_name: Hammer - first_name: Riikka full_name: Keski Filppula, Riikka last_name: Keski Filppula - first_name: Päivi full_name: Vieira, Päivi last_name: Vieira - first_name: Clara full_name: Hildebrandt, Clara last_name: Hildebrandt - first_name: Stephanie full_name: Sacharow, Stephanie last_name: Sacharow - first_name: Luca full_name: Maragliano, Luca last_name: Maragliano - first_name: Fabio full_name: Benfenati, Fabio last_name: Benfenati - first_name: Katherine full_name: Lachlan, Katherine last_name: Lachlan - first_name: Andreas full_name: Benneche, Andreas last_name: Benneche - first_name: Florence full_name: Petit, Florence last_name: Petit - first_name: Jean Madeleine full_name: de Sainte Agathe, Jean Madeleine last_name: de Sainte Agathe - first_name: Barbara full_name: Hallinan, Barbara last_name: Hallinan - first_name: Yue full_name: Si, Yue last_name: Si - first_name: Ingrid M full_name: Wentzensen, Ingrid M last_name: Wentzensen - first_name: Fanggeng full_name: Zou, Fanggeng last_name: Zou - first_name: Vinodh full_name: Narayanan, Vinodh last_name: Narayanan - first_name: Naomichi full_name: Matsumoto, Naomichi last_name: Matsumoto - first_name: Alessandra full_name: Boncristiano, Alessandra last_name: Boncristiano - first_name: Giancarlo full_name: la Marca, Giancarlo last_name: la Marca - first_name: Mitsuhiro full_name: Kato, Mitsuhiro last_name: Kato - first_name: Kristin full_name: Anderson, Kristin last_name: Anderson - first_name: Carmen full_name: Barba, Carmen last_name: Barba - first_name: Luisa full_name: Sturiale, Luisa last_name: Sturiale - first_name: Domenico full_name: Garozzo, Domenico last_name: Garozzo - first_name: Roberto full_name: Bei, Roberto last_name: Bei - first_name: Laura full_name: Masuelli, Laura last_name: Masuelli - first_name: Valerio full_name: Conti, Valerio last_name: Conti - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Anna full_name: Fassio, Anna last_name: Fassio citation: ama: 'Guerrini R, Mei D, Szigeti MK, et al. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. Brain. 2022;145(8):2687-2703. doi:10.1093/brain/awac145' apa: 'Guerrini, R., Mei, D., Szigeti, M. K., Pepe, S., Koenig, M. K., Von Allmen, G., … Fassio, A. (2022). Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. Brain. Oxford University Press. https://doi.org/10.1093/brain/awac145' chicago: 'Guerrini, Renzo, Davide Mei, Margit Katalin Szigeti, Sara Pepe, Mary Kay Koenig, Gretchen Von Allmen, Megan T Cho, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” Brain. Oxford University Press, 2022. https://doi.org/10.1093/brain/awac145.' ieee: 'R. Guerrini et al., “Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis,” Brain, vol. 145, no. 8. Oxford University Press, pp. 2687–2703, 2022.' ista: 'Guerrini R, Mei D, Szigeti MK, Pepe S, Koenig MK, Von Allmen G, Cho MT, McDonald K, Baker J, Bhambhani V, Powis Z, Rodan L, Nabbout R, Barcia G, Rosenfeld JA, Bacino CA, Mignot C, Power LH, Harris CJ, Marjanovic D, Møller RS, Hammer TB, Keski Filppula R, Vieira P, Hildebrandt C, Sacharow S, Maragliano L, Benfenati F, Lachlan K, Benneche A, Petit F, de Sainte Agathe JM, Hallinan B, Si Y, Wentzensen IM, Zou F, Narayanan V, Matsumoto N, Boncristiano A, la Marca G, Kato M, Anderson K, Barba C, Sturiale L, Garozzo D, Bei R, Masuelli L, Conti V, Novarino G, Fassio A. 2022. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. Brain. 145(8), 2687–2703.' mla: 'Guerrini, Renzo, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” Brain, vol. 145, no. 8, Oxford University Press, 2022, pp. 2687–703, doi:10.1093/brain/awac145.' short: R. Guerrini, D. Mei, M.K. Szigeti, S. Pepe, M.K. Koenig, G. Von Allmen, M.T. Cho, K. McDonald, J. Baker, V. Bhambhani, Z. Powis, L. Rodan, R. Nabbout, G. Barcia, J.A. Rosenfeld, C.A. Bacino, C. Mignot, L.H. Power, C.J. Harris, D. Marjanovic, R.S. Møller, T.B. Hammer, R. Keski Filppula, P. Vieira, C. Hildebrandt, S. Sacharow, L. Maragliano, F. Benfenati, K. Lachlan, A. Benneche, F. Petit, J.M. de Sainte Agathe, B. Hallinan, Y. Si, I.M. Wentzensen, F. Zou, V. Narayanan, N. Matsumoto, A. Boncristiano, G. la Marca, M. Kato, K. Anderson, C. Barba, L. Sturiale, D. Garozzo, R. Bei, L. Masuelli, V. Conti, G. Novarino, A. Fassio, Brain 145 (2022) 2687–2703. date_created: 2023-01-12T12:11:45Z date_published: 2022-08-01T00:00:00Z date_updated: 2026-06-18T17:24:52Z day: '01' ddc: - '570' department: - _id: GaNo doi: 10.1093/brain/awac145 ec_funded: 1 external_id: isi: - '000807770000001' pmid: - '35675510' fulldoi: https://doi.org/10.1093/brain/awac145 intvolume: ' 145' isi: 1 issue: '8' keyword: - Neurology (clinical) language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1093/brain/awac145 month: '08' oa: 1 oa_version: Published Version page: 2687-2703 pmid: 1 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: Brain publication_identifier: eissn: - 1460-2156 issn: - 0006-8950 publication_status: published publisher: Oxford University Press quality_controlled: '1' scopus_import: '1' status: public title: 'Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 145 year: '2022' ... --- _id: '12209' abstract: - lang: eng text: Embryo development requires biochemical signalling to generate patterns of cell fates and active mechanical forces to drive tissue shape changes. However, how these processes are coordinated, and how tissue patterning is preserved despite the cellular flows occurring during morphogenesis, remains poorly understood. Gastrulation is a crucial embryonic stage that involves both patterning and internalization of the mesendoderm germ layer tissue. Here we show that, in zebrafish embryos, a gradient in Nodal signalling orchestrates pattern-preserving internalization movements by triggering a motility-driven unjamming transition. In addition to its role as a morphogen determining embryo patterning, graded Nodal signalling mechanically subdivides the mesendoderm into a small fraction of highly protrusive leader cells, able to autonomously internalize via local unjamming, and less protrusive followers, which need to be pulled inwards by the leaders. The Nodal gradient further enforces a code of preferential adhesion coupling leaders to their immediate followers, resulting in a collective and ordered mode of internalization that preserves mesendoderm patterning. Integrating this dual mechanical role of Nodal signalling into minimal active particle simulations quantitatively predicts both physiological and experimentally perturbed internalization movements. This provides a quantitative framework for how a morphogen-encoded unjamming transition can bidirectionally couple tissue mechanics with patterning during complex three-dimensional morphogenesis. acknowledged_ssus: - _id: Bio - _id: LifeSc acknowledgement: "We thank K. Sampath, A. Pauli and Y. Bellaїche for feedback on the manuscript. We also thank the members of the Heisenberg group, in particular A. Schauer and F. Nur Arslan, for help, technical advice and discussions, and the Bioimaging and Life Science facilities at IST\r\nAustria for continuous support. We thank C. Flandoli for the artwork in the figures. This work was supported by postdoctoral fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P. and the European Union (European Research Council starting grant 851288 to É.H. and European Research Council advanced grant 742573 to C.-P.H.)." article_processing_charge: No article_type: original author: - first_name: Diana C full_name: Nunes Pinheiro, Diana C id: 2E839F16-F248-11E8-B48F-1D18A9856A87 last_name: Nunes Pinheiro orcid: 0000-0003-4333-7503 - first_name: Roland full_name: Kardos, Roland id: 4039350E-F248-11E8-B48F-1D18A9856A87 last_name: Kardos - 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: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 citation: ama: Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nature Physics. 2022;18(12):1482-1493. doi:10.1038/s41567-022-01787-6 apa: Nunes Pinheiro, D. C., Kardos, R., Hannezo, E. B., & Heisenberg, C.-P. J. (2022). Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-022-01787-6 chicago: Nunes Pinheiro, Diana C, Roland Kardos, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis via Motility-Driven Unjamming.” Nature Physics. Springer Nature, 2022. https://doi.org/10.1038/s41567-022-01787-6. ieee: D. C. Nunes Pinheiro, R. Kardos, E. B. Hannezo, and C.-P. J. Heisenberg, “Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming,” Nature Physics, vol. 18, no. 12. Springer Nature, pp. 1482–1493, 2022. ista: Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. 2022. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nature Physics. 18(12), 1482–1493. mla: Nunes Pinheiro, Diana C., et al. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis via Motility-Driven Unjamming.” Nature Physics, vol. 18, no. 12, Springer Nature, 2022, pp. 1482–93, doi:10.1038/s41567-022-01787-6. short: D.C. Nunes Pinheiro, R. Kardos, E.B. Hannezo, C.-P.J. Heisenberg, Nature Physics 18 (2022) 1482–1493. corr_author: '1' date_created: 2023-01-16T09:45:19Z date_published: 2022-12-01T00:00:00Z date_updated: 2025-04-14T07:46:59Z day: '01' ddc: - '570' department: - _id: CaHe - _id: EdHa doi: 10.1038/s41567-022-01787-6 ec_funded: 1 external_id: isi: - '000871319900002' file: - access_level: open_access checksum: c86a8e8d80d1bfc46d56a01e88a2526a content_type: application/pdf creator: dernst date_created: 2023-01-27T07:32:01Z date_updated: 2023-01-27T07:32:01Z file_id: '12412' file_name: 2022_NaturePhysics_Pinheiro.pdf file_size: 36703569 relation: main_file success: 1 file_date_updated: 2023-01-27T07:32:01Z fulldoi: https://doi.org/10.1038/s41567-022-01787-6 has_accepted_license: '1' intvolume: ' 18' isi: 1 issue: '12' keyword: - General Physics and Astronomy language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 1482-1493 project: - _id: 26520D1E-B435-11E9-9278-68D0E5697425 grant_number: ALTF 850-2017 name: Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation - _id: 26520D1E-B435-11E9-9278-68D0E5697425 grant_number: ALTF 850-2017 name: Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis - _id: 260F1432-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742573' name: Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation publication: Nature Physics publication_identifier: eissn: - 1745-2481 issn: - 1745-2473 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming 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: 18 year: '2022' ... --- _id: '12239' abstract: - lang: eng text: Biological systems are the sum of their dynamic three-dimensional (3D) parts. Therefore, it is critical to study biological structures in 3D and at high resolution to gain insights into their physiological functions. Electron microscopy of metal replicas of unroofed cells and isolated organelles has been a key technique to visualize intracellular structures at nanometer resolution. However, many of these methods require specialized equipment and personnel to complete them. Here, we present novel accessible methods to analyze biological structures in unroofed cells and biochemically isolated organelles in 3D and at nanometer resolution, focusing on Arabidopsis clathrin-coated vesicles (CCVs). While CCVs are essential trafficking organelles, their detailed structural information is lacking due to their poor preservation when observed via classical electron microscopy protocols experiments. First, we establish a method to visualize CCVs in unroofed cells using scanning transmission electron microscopy tomography, providing sufficient resolution to define the clathrin coat arrangements. Critically, the samples are prepared directly on electron microscopy grids, removing the requirement to use extremely corrosive acids, thereby enabling the use of this method in any electron microscopy lab. Secondly, we demonstrate that this standardized sample preparation allows the direct comparison of isolated CCV samples with those visualized in cells. Finally, to facilitate the high-throughput and robust screening of metal replicated samples, we provide a deep learning analysis method to screen the “pseudo 3D” morphologies of CCVs imaged with 2D modalities. Collectively, our work establishes accessible ways to examine the 3D structure of biological samples and provide novel insights into the structure of plant CCVs. acknowledged_ssus: - _id: EM-Fac - _id: LifeSc - _id: Bio acknowledgement: A.J. is supported by funding from the Austrian Science Fund I3630B25 (to J.F.). This research was supported by the Scientific Service Units of Institute of Science and Technology Austria (ISTA) through resources provided by the Electron Microscopy Facility, Lab Support Facility, and the Imaging and Optics Facility. We acknowledge Prof. David Robinson (Heidelberg) and Prof. Jan Traas (Lyon) for making us aware of previously published classical on-grid preparation methods. No conflict of interest declared. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Alexander J full_name: Johnson, Alexander J id: 46A62C3A-F248-11E8-B48F-1D18A9856A87 last_name: Johnson orcid: 0000-0002-2739-8843 - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - 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: Tommaso full_name: Costanzo, Tommaso id: D93824F4-D9BA-11E9-BB12-F207E6697425 last_name: Costanzo orcid: 0000-0001-9732-3815 - first_name: Dana A. full_name: Dahhan, Dana A. last_name: Dahhan - first_name: Sebastian Y. full_name: Bednarek, Sebastian Y. last_name: Bednarek - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 citation: ama: Johnson AJ, Kaufmann W, Sommer CM, et al. Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. Molecular Plant. 2022;15(10):1533-1542. doi:10.1016/j.molp.2022.09.003 apa: Johnson, A. J., Kaufmann, W., Sommer, C. M., Costanzo, T., Dahhan, D. A., Bednarek, S. Y., & Friml, J. (2022). Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. Molecular Plant. Elsevier. https://doi.org/10.1016/j.molp.2022.09.003 chicago: Johnson, Alexander J, Walter Kaufmann, Christoph M Sommer, Tommaso Costanzo, Dana A. Dahhan, Sebastian Y. Bednarek, and Jiří Friml. “Three-Dimensional Visualization of Planta Clathrin-Coated Vesicles at Ultrastructural Resolution.” Molecular Plant. Elsevier, 2022. https://doi.org/10.1016/j.molp.2022.09.003. ieee: A. J. Johnson et al., “Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution,” Molecular Plant, vol. 15, no. 10. Elsevier, pp. 1533–1542, 2022. ista: Johnson AJ, Kaufmann W, Sommer CM, Costanzo T, Dahhan DA, Bednarek SY, Friml J. 2022. Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution. Molecular Plant. 15(10), 1533–1542. mla: Johnson, Alexander J., et al. “Three-Dimensional Visualization of Planta Clathrin-Coated Vesicles at Ultrastructural Resolution.” Molecular Plant, vol. 15, no. 10, Elsevier, 2022, pp. 1533–42, doi:10.1016/j.molp.2022.09.003. short: A.J. Johnson, W. Kaufmann, C.M. Sommer, T. Costanzo, D.A. Dahhan, S.Y. Bednarek, J. Friml, Molecular Plant 15 (2022) 1533–1542. corr_author: '1' date_created: 2023-01-16T09:51:49Z date_published: 2022-10-03T00:00:00Z date_updated: 2025-04-15T07:32:09Z day: '03' ddc: - '580' department: - _id: JiFr - _id: EM-Fac - _id: Bio doi: 10.1016/j.molp.2022.09.003 external_id: isi: - '000882769800009' pmid: - '36081349' file: - access_level: open_access checksum: 04d5c12490052d03e4dc4412338a43dd content_type: application/pdf creator: dernst date_created: 2023-01-30T07:46:51Z date_updated: 2023-01-30T07:46:51Z file_id: '12435' file_name: 2022_MolecularPlant_Johnson.pdf file_size: 2307251 relation: main_file success: 1 file_date_updated: 2023-01-30T07:46:51Z fulldoi: https://doi.org/10.1016/j.molp.2022.09.003 has_accepted_license: '1' intvolume: ' 15' isi: 1 issue: '10' keyword: - Plant Science - Molecular Biology language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: 1533-1542 pmid: 1 project: - _id: 26538374-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03630 name: Molecular mechanisms of endocytic cargo recognition in plants publication: Molecular Plant publication_identifier: issn: - 1674-2052 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution 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: 15 year: '2022' ... --- OA_place: publisher _id: '12368' abstract: - lang: eng text: "Metazoan development relies on the formation and remodeling of cell-cell contacts. The \r\nbinding of adhesion receptors and remodeling of the actomyosin cell cortex at cell-cell \r\ninteraction sites have been implicated in cell-cell contact formation. Yet, how these two \r\nprocesses functionally interact to drive cell-cell contact expansion and strengthening \r\nremains unclear. Here, we study how primary germ layer progenitor cells from zebrafish \r\nbind to supported lipid bilayers (SLB) functionalized with E-cadherin ectodomains as an \r\nassay system for monitoring cell-cell contact formation at high spatiotemporal resolution. \r\nWe show that cell-cell contact formation represents a two-tiered process: E-cadherin\x02mediated downregulation of the small GTPase RhoA at the forming contact leads to both \r\ndepletion of Myosin-2 and decrease of F-actin. This is followed by centrifugal actin \r\nnetwork flows at the contact triggered by a sharp gradient of Myosin-2 at the rim of the \r\ncontact zone, with Myosin-2 displaying higher cortical localization outside than inside of \r\nthe contact. These centrifugal cortical actin flows, in turn, not only further dilute the actin \r\nnetwork at the contact disc, but also lead to an accumulation of both F-actin and E\x02cadherin at the contact rim. Eventually, this combination of actomyosin downregulation \r\nand flows at the contact contribute to the characteristic molecular organization implicated \r\nin contact formation and maintenance: depletion of cortical actomyosin at the contact disc, \r\ndriving contact expansion by lowering interfacial tension at the contact, and accumulation \r\nof both E-cadherin and F-actin at the contact rim, mechanically linking the contractile \r\ncortices of the adhering cells. Thus, using a biomimetic assay, we exemplify how \r\nadhesion signaling and cell mechanics function together to modulate the spatial \r\norganization of cell-cell contacts." acknowledged_ssus: - _id: LifeSc - _id: Bio - _id: NanoFab alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Feyza N full_name: Arslan, Feyza N id: 49DA7910-F248-11E8-B48F-1D18A9856A87 last_name: Arslan orcid: 0000-0001-5809-9566 citation: ama: Arslan FN. Remodeling of E-cadherin-mediated contacts via cortical  flows. 2022. doi:10.15479/at:ista:12153 apa: Arslan, F. N. (2022). Remodeling of E-cadherin-mediated contacts via cortical  flows. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12153 chicago: Arslan, Feyza N. “Remodeling of E-Cadherin-Mediated Contacts via Cortical  Flows.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12153. ieee: F. N. Arslan, “Remodeling of E-cadherin-mediated contacts via cortical  flows,” Institute of Science and Technology Austria, 2022. ista: Arslan FN. 2022. Remodeling of E-cadherin-mediated contacts via cortical  flows. Institute of Science and Technology Austria. mla: Arslan, Feyza N. Remodeling of E-Cadherin-Mediated Contacts via Cortical  Flows. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12153. short: F.N. Arslan, Remodeling of E-Cadherin-Mediated Contacts via Cortical  Flows, Institute of Science and Technology Austria, 2022. corr_author: '1' date_created: 2023-01-25T10:43:24Z date_published: 2022-09-29T00:00:00Z date_updated: 2026-06-18T19:47:50Z day: '29' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: CaHe doi: 10.15479/at:ista:12153 ec_funded: 1 file: - access_level: open_access checksum: e54a3e69b83ebf166544164afd25608e content_type: application/pdf creator: cchlebak date_created: 2023-01-25T10:52:46Z date_updated: 2023-01-25T10:52:46Z file_id: '12369' file_name: THESIS_FINAL_FArslan_pdfa.pdf file_size: 14581024 relation: main_file success: 1 file_date_updated: 2023-01-25T10:52:46Z fulldoi: https://doi.org/10.15479/at:ista:12153 has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '113' project: - _id: 260F1432-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742573' name: Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation publication_identifier: isbn: - '978-3-99078-025-1 ' issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '9350' relation: part_of_dissertation status: public status: public supervisor: - 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 title: Remodeling of E-cadherin-mediated contacts via cortical flows tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '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 University Press. 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 University Press, 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 University Press, 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 University Press, 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). corr_author: '1' date_created: 2022-02-25T07:52:11Z date_published: 2022-07-07T00:00:00Z date_updated: 2026-04-07T13:29:13Z day: '07' ddc: - '570' department: - _id: SiHi - _id: BjHo - _id: LifeSc - _id: EM-Fac doi: 10.1093/oons/kvac009 ec_funded: 1 external_id: pmid: - '38596707' 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 fulldoi: https://doi.org/10.1093/oons/kvac009 has_accepted_license: '1' intvolume: ' 1' issue: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version pmid: 1 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 University Press 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. corr_author: '1' date_created: 2021-08-06T09:09:11Z date_published: 2022-07-11T00:00:00Z date_updated: 2025-06-11T13:52:43Z 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' pmid: - '35817845' 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 fulldoi: https://doi.org/10.1038/s41590-022-01257-4 has_accepted_license: '1' intvolume: ' 23' isi: 1 language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: 1246-1255 pmid: 1 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 23 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). corr_author: '1' date_created: 2022-07-03T22:01:33Z date_published: 2022-07-15T00:00:00Z date_updated: 2026-08-12T08:45:16Z day: '15' ddc: - '610' department: - _id: SaSi doi: 10.1016/j.isci.2022.104580 ec_funded: 1 external_id: isi: - '000830428500005' pmid: - '35789843' 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 fulldoi: https://doi.org/10.1016/j.isci.2022.104580 has_accepted_license: '1' intvolume: ' 25' isi: 1 issue: '7' language: - iso: eng month: '07' oa: 1 oa_version: Published Version pmid: 1 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 - id: '20074' relation: dissertation_contains 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 25 year: '2022' ...