--- _id: '8951' abstract: - lang: eng text: Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions, such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks remains a major challenge. Here, we use a well-defined synthetic gene regulatory network to study how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one gene regulatory network with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Our results demonstrate that changes in local genetic context can place a single transcriptional unit within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual transcriptional units, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of gene regulatory networks. article_processing_charge: No author: - first_name: Anna A full_name: Nagy-Staron, Anna A id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87 last_name: Nagy-Staron orcid: 0000-0002-1391-8377 citation: ama: Nagy-Staron AA. Sequences of gene regulatory network permutations for the article “Local genetic context shapes the function of a gene regulatory network.” 2020. doi:10.15479/AT:ISTA:8951 apa: Nagy-Staron, A. A. (2020). Sequences of gene regulatory network permutations for the article “Local genetic context shapes the function of a gene regulatory network.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8951 chicago: Nagy-Staron, Anna A. “Sequences of Gene Regulatory Network Permutations for the Article ‘Local Genetic Context Shapes the Function of a Gene Regulatory Network.’” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8951. ieee: A. A. Nagy-Staron, “Sequences of gene regulatory network permutations for the article ‘Local genetic context shapes the function of a gene regulatory network.’” Institute of Science and Technology Austria, 2020. ista: Nagy-Staron AA. 2020. Sequences of gene regulatory network permutations for the article ‘Local genetic context shapes the function of a gene regulatory network’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:8951. mla: Nagy-Staron, Anna A. Sequences of Gene Regulatory Network Permutations for the Article “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8951. short: A.A. Nagy-Staron, (2020). contributor: - contributor_type: project_member first_name: Anna A id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87 last_name: Nagy-Staron - contributor_type: project_member first_name: Kathrin id: 3AEC8556-F248-11E8-B48F-1D18A9856A87 last_name: Tomasek - contributor_type: project_member first_name: Caroline last_name: Caruso Carter - contributor_type: project_member first_name: Elisabeth last_name: Sonnleitner - contributor_type: project_member first_name: Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X - contributor_type: project_member first_name: Tiago last_name: Paixão - contributor_type: project_manager first_name: Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 date_created: 2020-12-20T10:00:26Z date_published: 2020-12-21T00:00:00Z date_updated: 2024-02-21T12:41:57Z day: '21' ddc: - '570' department: - _id: CaGu doi: 10.15479/AT:ISTA:8951 file: - access_level: open_access checksum: f57862aeee1690c7effd2b1117d40ed1 content_type: text/plain creator: bkavcic date_created: 2020-12-20T09:52:52Z date_updated: 2020-12-20T09:52:52Z file_id: '8952' file_name: readme.txt file_size: 523 relation: main_file success: 1 - access_level: open_access checksum: f2c6d5232ec6d551b6993991e8689e9f content_type: application/octet-stream creator: bkavcic date_created: 2020-12-20T22:01:44Z date_updated: 2020-12-20T22:01:44Z file_id: '8954' file_name: GRNs Research depository.gb file_size: 379228 relation: main_file success: 1 file_date_updated: 2020-12-20T22:01:44Z has_accepted_license: '1' keyword: - Gene regulatory networks - Gene expression - Escherichia coli - Synthetic Biology license: https://creativecommons.org/licenses/by/4.0/ month: '12' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '9283' relation: used_in_publication status: public status: public title: Sequences of gene regulatory network permutations for the article "Local genetic context shapes the function of a gene regulatory network" tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '7383' abstract: - lang: eng text: Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature. article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 citation: ama: 'Grah R. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. 2020. doi:10.15479/AT:ISTA:7383' apa: 'Grah, R. (2020). Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7383' chicago: 'Grah, Rok. “Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7383.' ieee: 'R. Grah, “Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation.” Institute of Science and Technology Austria, 2020.' ista: 'Grah R. 2020. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation, Institute of Science and Technology Austria, 10.15479/AT:ISTA:7383.' mla: 'Grah, Rok. Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7383.' short: R. Grah, (2020). contributor: - contributor_type: project_leader first_name: Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 date_created: 2020-01-28T10:41:49Z date_published: 2020-01-28T00:00:00Z date_updated: 2024-02-21T12:42:31Z day: '28' department: - _id: CaGu - _id: GaTk doi: 10.15479/AT:ISTA:7383 file: - access_level: open_access checksum: 9d292cf5207b3829225f44c044cdb3fd content_type: application/zip creator: rgrah date_created: 2020-01-28T10:39:40Z date_updated: 2020-07-14T12:47:57Z file_id: '7384' file_name: Scripts.zip file_size: 73363365 relation: main_file - access_level: open_access checksum: 4076ceab32ef588cc233802bab24c1ab content_type: text/plain creator: rgrah date_created: 2020-01-28T10:39:30Z date_updated: 2020-07-14T12:47:57Z file_id: '7385' file_name: READ_ME_MAIN.txt file_size: 962 relation: main_file file_date_updated: 2020-07-14T12:47:57Z has_accepted_license: '1' keyword: - Matlab scripts - analysis of microfluidics - mathematical model month: '01' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '7652' relation: used_in_publication status: public status: public title: 'Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation' type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '7569' abstract: - lang: eng text: 'Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. In particular, positive or negative regulation can lead to activation of a gene in response to an external signal. Previous works proposed that the form of regulation of a gene correlates with its frequency of usage: positive regulation when the gene is frequently expressed and negative regulation when infrequently expressed. Such network design means that, in the absence of their regulators, the genes are found in their least required activity state, hence regulatory intervention is often necessary. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. To determine how the form of regulation affects the global crosstalk in the network, we used a mathematical model that includes multiple regulators and multiple target genes. We found that crosstalk depends non-monotonically on the availability of regulators. Our analysis showed that excess use of regulation entailed by the formerly suggested network design caused high crosstalk levels in a large part of the parameter space. We therefore considered the opposite ‘idle’ design, where the default unregulated state of genes is their frequently required activity state. We found, that ‘idle’ design minimized the use of regulation and thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae using transcription factors binding data. We demonstrated that even partial network data could suffice to estimate its global crosstalk, suggesting its applicability to additional organisms. We found that S. cerevisiae estimated crosstalk is lower than that of a random network, suggesting that natural selection reduces crosstalk. In summary, our study highlights a new type of protein production cost which is typically overlooked: that of regulatory interference caused by the presence of excess regulators in the cell. It demonstrates the importance of whole-network descriptions, which could show effects missed by single-gene models.' article_number: e1007642 article_processing_charge: No article_type: original author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Tamar full_name: Friedlander, Tamar last_name: Friedlander citation: ama: Grah R, Friedlander T. The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. 2020;16(2). doi:10.1371/journal.pcbi.1007642 apa: Grah, R., & Friedlander, T. (2020). The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007642 chicago: Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” PLOS Computational Biology. Public Library of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642. ieee: R. Grah and T. Friedlander, “The relation between crosstalk and gene regulation form revisited,” PLOS Computational Biology, vol. 16, no. 2. Public Library of Science, 2020. ista: Grah R, Friedlander T. 2020. The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. 16(2), e1007642. mla: Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” PLOS Computational Biology, vol. 16, no. 2, e1007642, Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642. short: R. Grah, T. Friedlander, PLOS Computational Biology 16 (2020). date_created: 2020-03-06T07:39:38Z date_published: 2020-02-25T00:00:00Z date_updated: 2023-09-12T11:02:24Z day: '25' ddc: - '000' - '570' department: - _id: CaGu - _id: GaTk doi: 10.1371/journal.pcbi.1007642 external_id: isi: - '000526725200019' file: - access_level: open_access checksum: 5239dd134dc6e1c71fe7b3ce2953da37 content_type: application/pdf creator: dernst date_created: 2020-03-09T15:12:21Z date_updated: 2020-07-14T12:48:00Z file_id: '7579' file_name: 2020_PlosCompBio_Grah.pdf file_size: 2209325 relation: main_file file_date_updated: 2020-07-14T12:48:00Z has_accepted_license: '1' intvolume: ' 16' isi: 1 issue: '2' language: - iso: eng month: '02' oa: 1 oa_version: Published Version publication: PLOS Computational Biology publication_identifier: issn: - 1553-7358 publication_status: published publisher: Public Library of Science quality_controlled: '1' related_material: record: - id: '9716' relation: research_data status: deleted - id: '9776' relation: research_data status: public - id: '9779' relation: used_in_publication status: public - id: '8155' relation: dissertation_contains status: public - id: '9777' relation: research_data status: public scopus_import: '1' status: public title: The relation between crosstalk and gene regulation form revisited 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: 16 year: '2020' ... --- _id: '7652' abstract: - lang: eng text: Organisms cope with change by taking advantage of transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. Here, we investigate whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations in Escherichia coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy-number and, therefore, expression-level polymorphisms. This amplification-mediated gene expression tuning (AMGET) occurs on timescales that are similar to canonical gene regulation and can respond to rapid environmental changes. Mathematical modelling shows that amplifications also tune gene expression in stochastic environments in which transcription-factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune the expression of any gene, without leaving any genomic signature. acknowledgement: We thank L. Hurst, N. Barton, M. Pleska, M. Steinrück, B. Kavcic and A. Staron for input on the manuscript, and To. Bergmiller and R. Chait for help with microfluidics experiments. I.T. is a recipient the OMV fellowship. R.G. is a recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences) Fellowship of the Austrian Academy of Sciences. article_processing_charge: No article_type: original author: - first_name: Isabella full_name: Tomanek, Isabella id: 3981F020-F248-11E8-B48F-1D18A9856A87 last_name: Tomanek orcid: 0000-0001-6197-363X - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: M. full_name: Lagator, M. last_name: Lagator - first_name: A. M. C. full_name: Andersson, A. M. C. last_name: Andersson - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 citation: ama: Tomanek I, Grah R, Lagator M, et al. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 2020;4(4):612-625. doi:10.1038/s41559-020-1132-7 apa: Tomanek, I., Grah, R., Lagator, M., Andersson, A. M. C., Bollback, J. P., Tkačik, G., & Guet, C. C. (2020). Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. Springer Nature. https://doi.org/10.1038/s41559-020-1132-7 chicago: Tomanek, Isabella, Rok Grah, M. Lagator, A. M. C. Andersson, Jonathan P Bollback, Gašper Tkačik, and Calin C Guet. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution. Springer Nature, 2020. https://doi.org/10.1038/s41559-020-1132-7. ieee: I. Tomanek et al., “Gene amplification as a form of population-level gene expression regulation,” Nature Ecology & Evolution, vol. 4, no. 4. Springer Nature, pp. 612–625, 2020. ista: Tomanek I, Grah R, Lagator M, Andersson AMC, Bollback JP, Tkačik G, Guet CC. 2020. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 4(4), 612–625. mla: Tomanek, Isabella, et al. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution, vol. 4, no. 4, Springer Nature, 2020, pp. 612–25, doi:10.1038/s41559-020-1132-7. short: I. Tomanek, R. Grah, M. Lagator, A.M.C. Andersson, J.P. Bollback, G. Tkačik, C.C. Guet, Nature Ecology & Evolution 4 (2020) 612–625. date_created: 2020-04-08T15:20:53Z date_published: 2020-04-01T00:00:00Z date_updated: 2024-03-25T23:30:20Z day: '01' ddc: - '570' department: - _id: GaTk - _id: CaGu doi: 10.1038/s41559-020-1132-7 external_id: isi: - '000519008300005' file: - access_level: open_access checksum: ef3bbf42023e30b2c24a6278025d2040 content_type: application/pdf creator: dernst date_created: 2020-10-09T09:56:01Z date_updated: 2020-10-09T09:56:01Z file_id: '8640' file_name: 2020_NatureEcolEvo_Tomanek.pdf file_size: 745242 relation: main_file success: 1 file_date_updated: 2020-10-09T09:56:01Z has_accepted_license: '1' intvolume: ' 4' isi: 1 issue: '4' language: - iso: eng month: '04' oa: 1 oa_version: Submitted Version page: 612-625 project: - _id: 267C84F4-B435-11E9-9278-68D0E5697425 name: Biophysically realistic genotype-phenotype maps for regulatory networks publication: Nature Ecology & Evolution publication_identifier: issn: - 2397-334X publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/ record: - id: '8155' relation: dissertation_contains status: public - id: '7383' relation: research_data status: public - id: '7016' relation: research_data status: public - id: '8653' relation: used_in_publication status: public scopus_import: '1' status: public title: Gene amplification as a form of population-level gene expression regulation type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 4 year: '2020' ... --- _id: '7675' abstract: - lang: eng text: 'In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene expression levels that is compatible with in vivo and in vitro bio-physical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In non-equilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal non-equilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in non-equilibrium models is in a tradeoff with gene expression noise, predicting bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space to a much smaller subspace that optimally realizes biological function prior to inference from data, our normative approach holds promise for mathematical models in systems biology.' article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Benjamin full_name: Zoller, Benjamin last_name: Zoller - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Grah R, Zoller B, Tkačik G. Normative models of enhancer function. bioRxiv. 2020. doi:10.1101/2020.04.08.029405 apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Normative models of enhancer function. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.08.029405 chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer Function.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.08.029405. ieee: R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,” bioRxiv. Cold Spring Harbor Laboratory, 2020. ista: Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv, 10.1101/2020.04.08.029405. mla: Grah, Rok, et al. “Normative Models of Enhancer Function.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.08.029405. short: R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020). date_created: 2020-04-23T10:12:51Z date_published: 2020-04-09T00:00:00Z date_updated: 2023-09-07T13:13:26Z day: '09' department: - _id: CaGu - _id: GaTk doi: 10.1101/2020.04.08.029405 language: - iso: eng main_file_link: - open_access: '1' url: 'https://doi.org/10.1101/2020.04.08.029405 ' month: '04' oa: 1 oa_version: Preprint project: - _id: 2665AAFE-B435-11E9-9278-68D0E5697425 grant_number: RGP0034/2018 name: Can evolution minimize spurious signaling crosstalk to reach optimal performance? - _id: 267C84F4-B435-11E9-9278-68D0E5697425 name: Biophysically realistic genotype-phenotype maps for regulatory networks publication: bioRxiv publication_status: published publisher: Cold Spring Harbor Laboratory related_material: record: - id: '8155' relation: dissertation_contains status: public status: public title: Normative models of enhancer function type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '7680' abstract: - lang: eng text: "Proteins and their complex dynamic interactions regulate cellular mechanisms from sensing and transducing extracellular signals, to mediating genetic responses, and sustaining or changing cell morphology. To manipulate these protein-protein interactions (PPIs) that govern the behavior and fate of cells, synthetically constructed, genetically encoded tools provide the means to precisely target proteins of interest (POIs), and control their subcellular localization and activity in vitro and in vivo. Ideal synthetic tools react to an orthogonal cue, i.e. a trigger that does not activate any other endogenous process, thereby allowing manipulation of the POI alone.\r\nIn optogenetics, naturally occurring photosensory domain from plants, algae and bacteria are re-purposed and genetically fused to POIs. Illumination with light of a specific wavelength triggers a conformational change that can mediate PPIs, such as dimerization or oligomerization. By using light as a trigger, these tools can be activated with high spatial and temporal precision, on subcellular and millisecond scales. Chemogenetic tools consist of protein domains that recognize and bind small molecules. By genetic fusion to POIs, these domains can mediate PPIs upon addition of their specific ligands, which are often synthetically designed to provide highly specific interactions and exhibit good bioavailability.\r\nMost optogenetic tools to mediate PPIs are based on well-studied photoreceptors responding to red, blue or near-UV light, leaving a striking gap in the green band of the visible light spectrum. Among both optogenetic and chemogenetic tools, there is an abundance of methods to induce PPIs, but tools to disrupt them require UV illumination, rely on covalent linkage and subsequent enzymatic cleavage or initially result in protein clustering of unknown stoichiometry.\r\nThis work describes how the recently structurally and photochemically characterized green-light responsive cobalamin-binding domains (CBDs) from bacterial transcription factors were re-purposed to function as a green-light responsive optogenetic tool. In contrast to previously engineered optogenetic tools, CBDs do not induce PPI, but rather confer a PPI already upon expression, which can be rapidly disrupted by illumination. This was employed to mimic inhibition of constitutive activity of a growth factor receptor, and successfully implement for cell signalling in mammalian cells and in vivo to rescue development in zebrafish. This work further describes the development and application of a chemically induced de-dimerizer (CDD) based on a recently identified and structurally described bacterial oxyreductase. CDD forms a dimer upon expression in absence of its cofactor, the flavin derivative F420. Safety and of domain expression and ligand exposure are demonstrated in vitro and in vivo in zebrafish. The system is further applied to inhibit cell signalling output from a chimeric receptor upon F420 treatment.\r\nCBDs and CDD expand the repertoire of synthetic tools by providing novel mechanisms of mediating PPIs, and by recognizing previously not utilized cues. In the future, they can readily be combined with existing synthetic tools to functionally manipulate PPIs in vitro and in vivo." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Stephanie full_name: Kainrath, Stephanie id: 32CFBA64-F248-11E8-B48F-1D18A9856A87 last_name: Kainrath citation: ama: Kainrath S. Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. 2020. doi:10.15479/AT:ISTA:7680 apa: Kainrath, S. (2020). Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7680 chicago: Kainrath, Stephanie. “Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7680. ieee: S. Kainrath, “Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals,” Institute of Science and Technology Austria, 2020. ista: Kainrath S. 2020. Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. Institute of Science and Technology Austria. mla: Kainrath, Stephanie. Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7680. short: S. Kainrath, Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals, Institute of Science and Technology Austria, 2020. date_created: 2020-04-24T16:00:51Z date_published: 2020-04-24T00:00:00Z date_updated: 2023-09-22T09:20:10Z day: '24' ddc: - '570' degree_awarded: PhD department: - _id: CaGu doi: 10.15479/AT:ISTA:7680 file: - access_level: open_access checksum: fb9a4468eb27be92690728e35c823796 content_type: application/pdf creator: stgingl date_created: 2020-04-28T11:19:21Z date_updated: 2021-10-31T23:30:05Z embargo: 2021-10-30 file_id: '7692' file_name: Thesis_without-signatures_PDFA.pdf file_size: 3268017 relation: main_file - access_level: closed checksum: f6c80ca97104a631a328cb79a2c53493 content_type: application/octet-stream creator: stgingl date_created: 2020-04-28T11:19:24Z date_updated: 2021-10-31T23:30:05Z embargo_to: open_access file_id: '7693' file_name: Thesis_without signatures.docx file_size: 5167703 relation: source_file file_date_updated: 2021-10-31T23:30:05Z has_accepted_license: '1' language: - iso: eng month: '04' oa: 1 oa_version: None page: '98' publication_identifier: eissn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '1028' relation: dissertation_contains status: public status: public supervisor: - first_name: Harald L full_name: Janovjak, Harald L id: 33BA6C30-F248-11E8-B48F-1D18A9856A87 last_name: Janovjak orcid: 0000-0002-8023-9315 title: Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '196' abstract: - lang: eng text: 'The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. ' acknowledgement: "M.L. is grateful to the members of the C Guet and G Tkacik groups for valuable comments and support. M.S. is grateful to Nikita Kalinin for inspiring communications.\r\n" article_processing_charge: No article_type: original arxiv: 1 author: - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Mikhail full_name: Shkolnikov, Mikhail id: 35084A62-F248-11E8-B48F-1D18A9856A87 last_name: Shkolnikov orcid: 0000-0002-4310-178X citation: ama: Lang M, Shkolnikov M. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. 2019;116(8):2821-2830. doi:10.1073/pnas.1812015116 apa: Lang, M., & Shkolnikov, M. (2019). Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1812015116 chicago: Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2019. https://doi.org/10.1073/pnas.1812015116. ieee: M. Lang and M. Shkolnikov, “Harmonic dynamics of the Abelian sandpile,” Proceedings of the National Academy of Sciences, vol. 116, no. 8. National Academy of Sciences, pp. 2821–2830, 2019. ista: Lang M, Shkolnikov M. 2019. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. 116(8), 2821–2830. mla: Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” Proceedings of the National Academy of Sciences, vol. 116, no. 8, National Academy of Sciences, 2019, pp. 2821–30, doi:10.1073/pnas.1812015116. short: M. Lang, M. Shkolnikov, Proceedings of the National Academy of Sciences 116 (2019) 2821–2830. date_created: 2018-12-11T11:45:08Z date_published: 2019-02-19T00:00:00Z date_updated: 2023-09-11T14:09:34Z day: '19' department: - _id: CaGu - _id: GaTk - _id: TaHa doi: 10.1073/pnas.1812015116 external_id: arxiv: - '1806.10823' isi: - '000459074400013' pmid: - ' 30728300' intvolume: ' 116' isi: 1 issue: '8' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1073/pnas.1812015116 month: '02' oa: 1 oa_version: Published Version page: 2821-2830 pmid: 1 publication: Proceedings of the National Academy of Sciences publication_identifier: eissn: - 1091-6490 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: link: - description: News on IST Webpage relation: press_release url: https://ist.ac.at/en/news/famous-sandpile-model-shown-to-move-like-a-traveling-sand-dune/ scopus_import: '1' status: public title: Harmonic dynamics of the Abelian sandpile type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 116 year: '2019' ... --- _id: '6717' abstract: - lang: eng text: With the recent publication by Silpe and Bassler (2019), considering phage detection of a bacterial quorum-sensing (QS) autoinducer, we now have as many as five examples of phage-associated intercellular communication (Table 1). Each potentially involves ecological inferences by phages as to concentrations of surrounding phage-infected or uninfected bacteria. While the utility of phage detection of bacterial QS molecules may at first glance appear to be straightforward, we suggest in this commentary that the underlying ecological explanation is unlikely to be simple. article_number: '1171' article_processing_charge: Yes (via OA deal) author: - first_name: Claudia full_name: Igler, Claudia id: 46613666-F248-11E8-B48F-1D18A9856A87 last_name: Igler - first_name: Stephen T. full_name: Abedon, Stephen T. last_name: Abedon citation: ama: 'Igler C, Abedon ST. Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 2019;10. doi:10.3389/fmicb.2019.01171' apa: 'Igler, C., & Abedon, S. T. (2019). Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. Frontiers. https://doi.org/10.3389/fmicb.2019.01171' chicago: 'Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology. Frontiers, 2019. https://doi.org/10.3389/fmicb.2019.01171.' ieee: 'C. Igler and S. T. Abedon, “Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision,” Frontiers in Microbiology, vol. 10. Frontiers, 2019.' ista: 'Igler C, Abedon ST. 2019. Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 10, 1171.' mla: 'Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology, vol. 10, 1171, Frontiers, 2019, doi:10.3389/fmicb.2019.01171.' short: C. Igler, S.T. Abedon, Frontiers in Microbiology 10 (2019). date_created: 2019-07-28T21:59:18Z date_published: 2019-06-03T00:00:00Z date_updated: 2023-08-29T06:41:20Z day: '03' ddc: - '570' department: - _id: CaGu doi: 10.3389/fmicb.2019.01171 external_id: isi: - '000470131200001' file: - access_level: open_access checksum: 317a06067e9a8e717bb55f23e0d77ba7 content_type: application/pdf creator: apreinsp date_created: 2019-07-29T07:51:54Z date_updated: 2020-07-14T12:47:38Z file_id: '6722' file_name: 2019_Frontiers_Igler.pdf file_size: 246151 relation: main_file file_date_updated: 2020-07-14T12:47:38Z has_accepted_license: '1' intvolume: ' 10' isi: 1 language: - iso: eng month: '06' oa: 1 oa_version: Published Version project: - _id: 251EE76E-B435-11E9-9278-68D0E5697425 grant_number: '24573' name: Design principles underlying genetic switch architecture (DOC Fellowship) publication: Frontiers in Microbiology publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: 'Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision' 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: 10 year: '2019' ... --- _id: '6784' abstract: - lang: eng text: Mathematical models have been used successfully at diverse scales of biological organization, ranging from ecology and population dynamics to stochastic reaction events occurring between individual molecules in single cells. Generally, many biological processes unfold across multiple scales, with mutations being the best studied example of how stochasticity at the molecular scale can influence outcomes at the population scale. In many other contexts, however, an analogous link between micro- and macro-scale remains elusive, primarily due to the challenges involved in setting up and analyzing multi-scale models. Here, we employ such a model to investigate how stochasticity propagates from individual biochemical reaction events in the bacterial innate immune system to the ecology of bacteria and bacterial viruses. We show analytically how the dynamics of bacterial populations are shaped by the activities of immunity-conferring enzymes in single cells and how the ecological consequences imply optimal bacterial defense strategies against viruses. Our results suggest that bacterial populations in the presence of viruses can either optimize their initial growth rate or their population size, with the first strategy favoring simple immunity featuring a single restriction modification system and the second strategy favoring complex bacterial innate immunity featuring several simultaneously active restriction modification systems. article_number: e1007168 article_processing_charge: No article_type: original author: - first_name: Jakob full_name: Ruess, Jakob id: 4A245D00-F248-11E8-B48F-1D18A9856A87 last_name: Ruess orcid: 0000-0003-1615-3282 - first_name: Maros full_name: Pleska, Maros id: 4569785E-F248-11E8-B48F-1D18A9856A87 last_name: Pleska orcid: 0000-0001-7460-7479 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Ruess J, Pleska M, Guet CC, Tkačik G. Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. 2019;15(7). doi:10.1371/journal.pcbi.1007168 apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168 chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational Biology. Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168. ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Molecular noise of innate immunity shapes bacteria-phage ecologies,” PLoS Computational Biology, vol. 15, no. 7. Public Library of Science, 2019. ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. 15(7), e1007168. mla: Ruess, Jakob, et al. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational Biology, vol. 15, no. 7, e1007168, Public Library of Science, 2019, doi:10.1371/journal.pcbi.1007168. short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15 (2019). date_created: 2019-08-11T21:59:19Z date_published: 2019-07-02T00:00:00Z date_updated: 2023-08-29T07:10:06Z day: '02' ddc: - '570' department: - _id: CaGu - _id: GaTk doi: 10.1371/journal.pcbi.1007168 external_id: isi: - '000481577700032' file: - access_level: open_access checksum: 7ded4721b41c2a0fc66a1c634540416a content_type: application/pdf creator: dernst date_created: 2019-08-12T12:27:26Z date_updated: 2020-07-14T12:47:40Z file_id: '6803' file_name: 2019_PlosComputBiology_Ruess.pdf file_size: 2200003 relation: main_file file_date_updated: 2020-07-14T12:47:40Z has_accepted_license: '1' intvolume: ' 15' isi: 1 issue: '7' language: - iso: eng month: '07' oa: 1 oa_version: Published Version project: - _id: 251D65D8-B435-11E9-9278-68D0E5697425 grant_number: '24210' name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level - _id: 251BCBEC-B435-11E9-9278-68D0E5697425 grant_number: RGY0079/2011 name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems publication: PLoS Computational Biology publication_identifier: eissn: - 1553-7358 publication_status: published publisher: Public Library of Science quality_controlled: '1' related_material: record: - id: '9786' relation: research_data status: public scopus_import: '1' status: public title: Molecular noise of innate immunity shapes bacteria-phage ecologies 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: '2019' ... --- _id: '7016' abstract: - lang: eng text: Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature. article_processing_charge: No author: - first_name: Isabella full_name: Tomanek, Isabella id: 3981F020-F248-11E8-B48F-1D18A9856A87 last_name: Tomanek orcid: 0000-0001-6197-363X citation: ama: Tomanek I. Data for the paper “Gene amplification as a form of population-level gene expression regulation.” 2019. doi:10.15479/AT:ISTA:7016 apa: Tomanek, I. (2019). Data for the paper “Gene amplification as a form of population-level gene expression regulation.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7016 chicago: Tomanek, Isabella. “Data for the Paper ‘Gene Amplification as a Form of Population-Level Gene Expression Regulation.’” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:7016. ieee: I. Tomanek, “Data for the paper ‘Gene amplification as a form of population-level gene expression regulation.’” Institute of Science and Technology Austria, 2019. ista: Tomanek I. 2019. Data for the paper ‘Gene amplification as a form of population-level gene expression regulation’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:7016. mla: Tomanek, Isabella. Data for the Paper “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:7016. short: I. Tomanek, (2019). contributor: - contributor_type: project_leader first_name: Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 date_created: 2019-11-13T09:07:31Z date_published: 2019-11-13T00:00:00Z date_updated: 2024-02-21T12:45:25Z day: '13' ddc: - '576' department: - _id: CaGu doi: 10.15479/AT:ISTA:7016 file: - access_level: open_access checksum: 72441055043eda4cbf1398a422e2c118 content_type: application/octet-stream creator: itomanek date_created: 2019-11-13T08:52:21Z date_updated: 2020-07-14T12:47:47Z description: Illumina whole genome sequence data for Locus 1 - amplified. file_id: '7017' file_name: D8_S35_R2_001.fastq file_size: 2456192500 relation: main_file title: Locus1_amplified - access_level: open_access checksum: a4ac50bf655d9c751f0305ade5c2ee16 content_type: application/octet-stream creator: itomanek date_created: 2019-11-13T08:52:59Z date_updated: 2020-07-14T12:47:47Z description: Illumina whole genome sequence data for Locus 1 - ancestral. file_id: '7018' file_name: IT028_S11_R2_001.fastq file_size: 2833452234 relation: main_file title: Locus1_ancestral - access_level: open_access checksum: 5b227708ff478ca06e3f0448a4efdc2f content_type: application/octet-stream creator: itomanek date_created: 2019-11-13T08:54:10Z date_updated: 2020-07-14T12:47:47Z description: Illumina whole genome sequence data for Locus 1 - amplified, after DOG-selection. file_id: '7019' file_name: D8-DOG1_S47_R2_001.fastq file_size: 2878017264 relation: main_file title: Locus1_amplified_DOG - access_level: open_access checksum: d9550a4c044116075fa83f8f2ea31d6f content_type: application/octet-stream creator: itomanek date_created: 2019-11-13T08:54:27Z date_updated: 2020-07-14T12:47:47Z description: Illumina whole genome sequence data for Locus 2 - amplified. file_id: '7020' file_name: D4_S71_R2_001.fastq file_size: 2180826995 relation: main_file title: Locus2_amplified - access_level: open_access checksum: 466ceb302c020ac013007a879fcde69d content_type: application/octet-stream creator: itomanek date_created: 2019-11-13T08:55:58Z date_updated: 2020-07-14T12:47:47Z description: Illumina whole genome sequence data for Locus 2 - ancestral. file_id: '7021' file_name: IT030_S23_R2_001.fastq file_size: 2108826444 relation: main_file title: Locus2_ancestral - access_level: open_access checksum: 8aeb1da771713c7baa5a847eff889604 content_type: application/octet-stream creator: itomanek date_created: 2019-11-21T12:31:01Z date_updated: 2020-07-14T12:47:47Z description: Illumina whole genome sequence data for Locus 2 - amplified, after DOG-selection. file_id: '7092' file_name: D4-DOG1_S83_R2_001.fastq file_size: 3144330494 relation: main_file title: Locus2_amplified_DOG - access_level: open_access checksum: bf7d4b053f14af4655fb5574209fdb2d content_type: application/zip creator: itomanek date_created: 2020-01-14T11:22:27Z date_updated: 2020-07-14T12:47:47Z description: Compressed genbank file format containing the sequence of the chromosomal reporter gene cassette. file_id: '7273' file_name: galK_dual_reporter_cassette.gb.zip file_size: 4179 relation: main_file title: DNA sequence of the chromosomal reporter gene cassette - access_level: open_access checksum: 5e91cee2eff6f4a7cde456c6fb07c2ff content_type: text/plain creator: dernst date_created: 2020-01-15T14:15:55Z date_updated: 2020-07-14T12:47:47Z file_id: '7335' file_name: Readme_7016.txt file_size: 435 relation: main_file title: Read_me_sequence_data - access_level: open_access checksum: 5e6745dcfb9c1b11dd935ac3ee45fe33 content_type: application/zip creator: itomanek date_created: 2020-01-22T15:44:16Z date_updated: 2020-07-14T12:47:47Z description: FACS data associated with Fig. 2c - see read_me_FACS file_id: '7351' file_name: FACS_data.xlsx.zip file_size: 3765861 relation: main_file title: FACS data - access_level: open_access checksum: a85caf092ae4b17668f70af2d93fad00 content_type: text/rtf creator: itomanek date_created: 2020-01-22T15:44:16Z date_updated: 2020-07-14T12:47:47Z file_id: '7352' file_name: read_me_FACS.rtf file_size: 4996 relation: main_file - access_level: open_access checksum: fd8ba5d75d24e47ddf7e70bfdadb40d4 content_type: text/rtf creator: itomanek date_created: 2020-01-22T15:44:16Z date_updated: 2020-07-14T12:47:47Z file_id: '7353' file_name: read_me_microfluidics.rtf file_size: 868 relation: main_file - access_level: open_access checksum: 69c5dc5ca5c069a138183c934acc1778 content_type: application/zip creator: itomanek date_created: 2020-01-22T15:44:17Z date_updated: 2020-07-14T12:47:47Z description: microfluidics time trace data - see read_me_microfluidics file_id: '7354' file_name: microfuidics_data.zip file_size: 8141727 relation: main_file title: microfluidics data file_date_updated: 2020-07-14T12:47:47Z has_accepted_license: '1' keyword: - Escherichia coli - gene amplification - galactose - DOG - experimental evolution - Illumina sequence data - FACS data - microfluidics data month: '11' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '7652' relation: used_in_publication status: public status: public title: Data for the paper "Gene amplification as a form of population-level gene expression regulation" type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2019' ... --- _id: '7147' abstract: - lang: eng text: "The expression of a gene is characterised by its transcription factors and the function processing them. If the transcription factors are not affected by gene products, the regulating function is often represented as a combinational logic circuit, where the outputs (product) are determined by current input values (transcription factors) only, and are hence independent on their relative arrival times. However, the simultaneous arrival of transcription factors (TFs) in genetic circuits is a strong assumption, given that the processes of transcription and translation of a gene into a protein introduce intrinsic time delays and that there is no global synchronisation among the arrival times of different molecular species at molecular targets.\r\n\r\nIn this paper, we construct an experimentally implementable genetic circuit with two inputs and a single output, such that, in presence of small delays in input arrival, the circuit exhibits qualitatively distinct observable phenotypes. In particular, these phenotypes are long lived transients: they all converge to a single value, but so slowly, that they seem stable for an extended time period, longer than typical experiment duration. We used rule-based language to prototype our circuit, and we implemented a search for finding the parameter combinations raising the phenotypes of interest.\r\n\r\nThe behaviour of our prototype circuit has wide implications. First, it suggests that GRNs can exploit event timing to create phenotypes. Second, it opens the possibility that GRNs are using event timing to react to stimuli and memorise events, without explicit feedback in regulation. From the modelling perspective, our prototype circuit demonstrates the critical importance of analysing the transient dynamics at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions." alternative_title: - LNCS article_processing_charge: No author: - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 - first_name: Claudia full_name: Igler, Claudia id: 46613666-F248-11E8-B48F-1D18A9856A87 last_name: Igler - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 - first_name: Ali full_name: Sezgin, Ali id: 4C7638DA-F248-11E8-B48F-1D18A9856A87 last_name: Sezgin citation: ama: 'Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. Transient memory in gene regulation. In: 17th International Conference on Computational Methods in Systems Biology. Vol 11773. Springer Nature; 2019:155-187. doi:10.1007/978-3-030-31304-3_9' apa: 'Guet, C. C., Henzinger, T. A., Igler, C., Petrov, T., & Sezgin, A. (2019). Transient memory in gene regulation. In 17th International Conference on Computational Methods in Systems Biology (Vol. 11773, pp. 155–187). Trieste, Italy: Springer Nature. https://doi.org/10.1007/978-3-030-31304-3_9' chicago: Guet, Calin C, Thomas A Henzinger, Claudia Igler, Tatjana Petrov, and Ali Sezgin. “Transient Memory in Gene Regulation.” In 17th International Conference on Computational Methods in Systems Biology, 11773:155–87. Springer Nature, 2019. https://doi.org/10.1007/978-3-030-31304-3_9. ieee: C. C. Guet, T. A. Henzinger, C. Igler, T. Petrov, and A. Sezgin, “Transient memory in gene regulation,” in 17th International Conference on Computational Methods in Systems Biology, Trieste, Italy, 2019, vol. 11773, pp. 155–187. ista: 'Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. 2019. Transient memory in gene regulation. 17th International Conference on Computational Methods in Systems Biology. CMSB: Computational Methods in Systems Biology, LNCS, vol. 11773, 155–187.' mla: Guet, Calin C., et al. “Transient Memory in Gene Regulation.” 17th International Conference on Computational Methods in Systems Biology, vol. 11773, Springer Nature, 2019, pp. 155–87, doi:10.1007/978-3-030-31304-3_9. short: C.C. Guet, T.A. Henzinger, C. Igler, T. Petrov, A. Sezgin, in:, 17th International Conference on Computational Methods in Systems Biology, Springer Nature, 2019, pp. 155–187. conference: end_date: 2019-09-20 location: Trieste, Italy name: 'CMSB: Computational Methods in Systems Biology' start_date: 2019-09-18 date_created: 2019-12-04T16:07:50Z date_published: 2019-09-17T00:00:00Z date_updated: 2023-09-06T11:18:08Z day: '17' department: - _id: CaGu - _id: ToHe doi: 10.1007/978-3-030-31304-3_9 external_id: isi: - '000557875100009' intvolume: ' 11773' isi: 1 language: - iso: eng month: '09' oa_version: None page: 155-187 project: - _id: 25F42A32-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z211 name: The Wittgenstein Prize - _id: 251EE76E-B435-11E9-9278-68D0E5697425 grant_number: '24573' name: Design principles underlying genetic switch architecture publication: 17th International Conference on Computational Methods in Systems Biology publication_identifier: eissn: - 1611-3349 isbn: - '9783030313036' - '9783030313043' issn: - 0302-9743 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Transient memory in gene regulation type: conference user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 11773 year: '2019' ... --- _id: '6371' abstract: - lang: eng text: "Decades of studies have revealed the mechanisms of gene regulation in molecular detail. We make use of such well-described regulatory systems to explore how the molecular mechanisms of protein-protein and protein-DNA interactions shape the dynamics and evolution of gene regulation. \r\n\r\ni) We uncover how the biophysics of protein-DNA binding determines the potential of regulatory networks to evolve and adapt, which can be captured using a simple mathematical model. \r\nii) The evolution of regulatory connections can lead to a significant amount of crosstalk between binding proteins. We explore the effect of crosstalk on gene expression from a target promoter, which seems to be modulated through binding competition at non-specific DNA sites. \r\niii) We investigate how the very same biophysical characteristics as in i) can generate significant fitness costs for cells through global crosstalk, meaning non-specific DNA binding across the genomic background. \r\niv) Binding competition between proteins at a target promoter is a prevailing regulatory feature due to the prevalence of co-regulation at bacterial promoters. However, the dynamics of these systems are not always straightforward to determine even if the molecular mechanisms of regulation are known. A detailed model of the biophysical interactions reveals that interference between the regulatory proteins can constitute a new, generic form of system memory that records the history of the input signals at the promoter. \r\n\r\nWe demonstrate how the biophysics of protein-DNA binding can be harnessed to investigate the principles that shape and ultimately limit cellular gene regulation. These results provide a basis for studies of higher-level functionality, which arises from the underlying regulation. \ \r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Claudia full_name: Igler, Claudia id: 46613666-F248-11E8-B48F-1D18A9856A87 last_name: Igler citation: ama: Igler C. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. 2019. doi:10.15479/AT:ISTA:6371 apa: Igler, C. (2019). On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6371 chicago: Igler, Claudia. “On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6371. ieee: C. Igler, “On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation,” Institute of Science and Technology Austria, 2019. ista: Igler C. 2019. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. Institute of Science and Technology Austria. mla: Igler, Claudia. On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6371. short: C. Igler, On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation, Institute of Science and Technology Austria, 2019. date_created: 2019-05-03T11:55:51Z date_published: 2019-05-03T00:00:00Z date_updated: 2024-02-21T13:45:52Z day: '03' ddc: - '576' - '579' degree_awarded: PhD department: - _id: CaGu doi: 10.15479/AT:ISTA:6371 file: - access_level: open_access checksum: c0085d47c58c9cbcab1b0a783480f6da content_type: application/pdf creator: cigler date_created: 2019-05-03T11:54:52Z date_updated: 2021-02-11T11:17:13Z embargo: 2020-05-02 file_id: '6373' file_name: IglerClaudia_OntheNatureofGeneRegulatoryDesign.pdf file_size: 12597663 relation: main_file - access_level: closed checksum: 2eac954de1c8bbf7e6fb35ed0221ae8c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cigler date_created: 2019-05-03T11:54:54Z date_updated: 2020-07-14T12:47:28Z embargo_to: open_access file_id: '6374' file_name: IglerClaudia_OntheNatureofGeneRegulatoryDesign.docx file_size: 34644426 relation: source_file file_date_updated: 2021-02-11T11:17:13Z has_accepted_license: '1' keyword: - gene regulation - biophysics - transcription factor binding - bacteria language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '152' project: - _id: 251EE76E-B435-11E9-9278-68D0E5697425 grant_number: '24573' name: Design principles underlying genetic switch architecture (DOC Fellowship) publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '67' relation: part_of_dissertation status: public - id: '5585' relation: popular_science status: public status: public supervisor: - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 title: On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6465' abstract: - lang: eng text: Tight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner. Using the well-established tetracycline gene-regulation system as a model, we show that the dynamics of protein expression can be tuned by fusing appropriate degron tags to gene regulators. Next, we apply this degron library to tune a synthetic pulse-generating circuit in mammalian cells. With this toolbox we establish a set of pulse generators with tailored pulse lengths and magnitudes of protein expression. This methodology will prove useful in the functional roles of essential proteins, fine-tuning of gene-expression systems, and enabling a higher complexity in the design of synthetic biological systems in mammalian cells. article_number: '2013' article_processing_charge: No author: - first_name: Hélène full_name: Chassin, Hélène last_name: Chassin - first_name: Marius full_name: Müller, Marius last_name: Müller - first_name: Marcel full_name: Tigges, Marcel last_name: Tigges - first_name: Leo full_name: Scheller, Leo last_name: Scheller - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Martin full_name: Fussenegger, Martin last_name: Fussenegger citation: ama: Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. A modular degron library for synthetic circuits in mammalian cells. Nature Communications. 2019;10(1). doi:10.1038/s41467-019-09974-5 apa: Chassin, H., Müller, M., Tigges, M., Scheller, L., Lang, M., & Fussenegger, M. (2019). A modular degron library for synthetic circuits in mammalian cells. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-09974-5 chicago: Chassin, Hélène, Marius Müller, Marcel Tigges, Leo Scheller, Moritz Lang, and Martin Fussenegger. “A Modular Degron Library for Synthetic Circuits in Mammalian Cells.” Nature Communications. Springer Nature, 2019. https://doi.org/10.1038/s41467-019-09974-5. ieee: H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, and M. Fussenegger, “A modular degron library for synthetic circuits in mammalian cells,” Nature Communications, vol. 10, no. 1. Springer Nature, 2019. ista: Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. 2019. A modular degron library for synthetic circuits in mammalian cells. Nature Communications. 10(1), 2013. mla: Chassin, Hélène, et al. “A Modular Degron Library for Synthetic Circuits in Mammalian Cells.” Nature Communications, vol. 10, no. 1, 2013, Springer Nature, 2019, doi:10.1038/s41467-019-09974-5. short: H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, M. Fussenegger, Nature Communications 10 (2019). date_created: 2019-05-19T21:59:14Z date_published: 2019-05-01T00:00:00Z date_updated: 2023-08-25T10:33:51Z day: '01' ddc: - '570' department: - _id: CaGu doi: 10.1038/s41467-019-09974-5 external_id: isi: - '000466338600006' file: - access_level: open_access checksum: e214d3e4f8c81e35981583c4569b51b8 content_type: application/pdf creator: dernst date_created: 2019-05-20T07:33:54Z date_updated: 2020-07-14T12:47:31Z file_id: '6471' file_name: 2019_NatureComm_Chassin.pdf file_size: 1191827 relation: main_file file_date_updated: 2020-07-14T12:47:31Z has_accepted_license: '1' intvolume: ' 10' isi: 1 issue: '1' language: - iso: eng month: '05' oa: 1 oa_version: Published Version publication: Nature Communications publication_identifier: eissn: - '20411723' publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: erratum url: https://doi.org/10.1038/s41467-023-36111-0 scopus_import: '1' status: public title: A modular degron library for synthetic circuits in mammalian cells tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 10 year: '2019' ... --- _id: '138' abstract: - lang: eng text: Autoregulation is the direct modulation of gene expression by the product of the corresponding gene. Autoregulation of bacterial gene expression has been mostly studied at the transcriptional level, when a protein acts as the cognate transcriptional repressor. A recent study investigating dynamics of the bacterial toxin–antitoxin MazEF system has shown how autoregulation at both the transcriptional and post-transcriptional levels affects the heterogeneity of Escherichia coli populations. Toxin–antitoxin systems hold a crucial but still elusive part in bacterial response to stress. This perspective highlights how these modules can also serve as a great model system for investigating basic concepts in gene regulation. However, as the genomic background and environmental conditions substantially influence toxin activation, it is important to study (auto)regulation of toxin–antitoxin systems in well-defined setups as well as in conditions that resemble the environmental niche. article_processing_charge: Yes (via OA deal) author: - first_name: Nela full_name: Nikolic, Nela id: 42D9CABC-F248-11E8-B48F-1D18A9856A87 last_name: Nikolic orcid: 0000-0001-9068-6090 citation: ama: 'Nikolic N. Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system. Current Genetics. 2019;65(1):133-138. doi:10.1007/s00294-018-0879-8' apa: 'Nikolic, N. (2019). Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system. Current Genetics. Springer. https://doi.org/10.1007/s00294-018-0879-8' chicago: 'Nikolic, Nela. “Autoregulation of Bacterial Gene Expression: Lessons from the MazEF Toxin–Antitoxin System.” Current Genetics. Springer, 2019. https://doi.org/10.1007/s00294-018-0879-8.' ieee: 'N. Nikolic, “Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system,” Current Genetics, vol. 65, no. 1. Springer, pp. 133–138, 2019.' ista: 'Nikolic N. 2019. Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system. Current Genetics. 65(1), 133–138.' mla: 'Nikolic, Nela. “Autoregulation of Bacterial Gene Expression: Lessons from the MazEF Toxin–Antitoxin System.” Current Genetics, vol. 65, no. 1, Springer, 2019, pp. 133–38, doi:10.1007/s00294-018-0879-8.' short: N. Nikolic, Current Genetics 65 (2019) 133–138. date_created: 2018-12-11T11:44:50Z date_published: 2019-02-01T00:00:00Z date_updated: 2023-09-08T13:23:42Z day: '01' ddc: - '570' department: - _id: CaGu doi: 10.1007/s00294-018-0879-8 ec_funded: 1 external_id: isi: - '000456958800017' file: - access_level: open_access checksum: 6779708b0b632a1a6ed28c56f5161142 content_type: application/pdf creator: dernst date_created: 2019-02-06T07:50:58Z date_updated: 2020-07-14T12:44:47Z file_id: '5930' file_name: 2019_CurrentGenetics_Nikolic.pdf file_size: 776399 relation: main_file file_date_updated: 2020-07-14T12:44:47Z has_accepted_license: '1' intvolume: ' 65' isi: 1 issue: '1' language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: 133-138 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Current Genetics publication_status: published publisher: Springer publist_id: '7785' quality_controlled: '1' scopus_import: '1' status: public title: 'Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system' 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 65 year: '2019' ... --- _id: '9786' article_processing_charge: No author: - first_name: Jakob full_name: Ruess, Jakob id: 4A245D00-F248-11E8-B48F-1D18A9856A87 last_name: Ruess orcid: 0000-0003-1615-3282 - first_name: Maros full_name: Pleska, Maros id: 4569785E-F248-11E8-B48F-1D18A9856A87 last_name: Pleska orcid: 0000-0001-7460-7479 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Ruess J, Pleska M, Guet CC, Tkačik G. Supporting text and results. 2019. doi:10.1371/journal.pcbi.1007168.s001 apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Supporting text and results. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168.s001 chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Supporting Text and Results.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.s001. ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Supporting text and results.” Public Library of Science, 2019. ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Supporting text and results, Public Library of Science, 10.1371/journal.pcbi.1007168.s001. mla: Ruess, Jakob, et al. Supporting Text and Results. Public Library of Science, 2019, doi:10.1371/journal.pcbi.1007168.s001. short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019). date_created: 2021-08-06T08:23:43Z date_published: 2019-07-02T00:00:00Z date_updated: 2023-08-29T07:10:05Z day: '02' department: - _id: CaGu - _id: GaTk doi: 10.1371/journal.pcbi.1007168.s001 month: '07' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '6784' relation: used_in_publication status: public status: public title: Supporting text and results type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2019' ... --- _id: '26' abstract: - lang: eng text: Expression of genes is a fundamental molecular phenotype that is subject to evolution by different types of mutations. Both the rate and the effect of mutations may depend on the DNA sequence context of a particular gene or a particular promoter sequence. In this thesis I investigate the nature of this dependence using simple genetic systems in Escherichia coli. With these systems I explore the evolution of constitutive gene expression from random starting sequences at different loci on the chromosome and at different locations in sequence space. First, I dissect chromosomal neighborhood effects that underlie locus-dependent differences in the potential of a gene under selection to become more highly expressed. Next, I find that the effects of point mutations in promoter sequences are dependent on sequence context, and that an existing energy matrix model performs poorly in predicting relative expression of unrelated sequences. Finally, I show that a substantial fraction of random sequences contain functional promoters and I present an extended thermodynamic model that predicts promoter strength in full sequence space. Taken together, these results provide new insights and guides on how to integrate information on sequence context to improve our qualitative and quantitative understanding of bacterial gene expression, with implications for rapid evolution of drug resistance, de novo evolution of genes, and horizontal gene transfer. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Magdalena full_name: Steinrück, Magdalena id: 2C023F40-F248-11E8-B48F-1D18A9856A87 last_name: Steinrück orcid: 0000-0003-1229-9719 citation: ama: Steinrück M. The influence of sequence context on the evolution of bacterial gene expression. 2018. doi:10.15479/AT:ISTA:th1059 apa: Steinrück, M. (2018). The influence of sequence context on the evolution of bacterial gene expression. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1059 chicago: Steinrück, Magdalena. “The Influence of Sequence Context on the Evolution of Bacterial Gene Expression.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1059. ieee: M. Steinrück, “The influence of sequence context on the evolution of bacterial gene expression,” Institute of Science and Technology Austria, 2018. ista: Steinrück M. 2018. The influence of sequence context on the evolution of bacterial gene expression. Institute of Science and Technology Austria. mla: Steinrück, Magdalena. The Influence of Sequence Context on the Evolution of Bacterial Gene Expression. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th1059. short: M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial Gene Expression, Institute of Science and Technology Austria, 2018. date_created: 2018-12-11T11:44:14Z date_published: 2018-10-30T00:00:00Z date_updated: 2023-09-07T12:48:43Z day: '30' ddc: - '576' - '579' degree_awarded: PhD department: - _id: CaGu doi: 10.15479/AT:ISTA:th1059 file: - access_level: closed checksum: 413cbce1cd1debeae3abe2a25dbc70d1 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dernst date_created: 2019-02-08T10:51:22Z date_updated: 2020-07-14T12:45:43Z embargo_to: open_access file_id: '5941' file_name: Thesis_Steinrueck_final.docx file_size: 9190845 relation: source_file - access_level: open_access checksum: 3def8b7854c8b42d643597ce0215efac content_type: application/pdf creator: dernst date_created: 2019-02-08T10:51:22Z date_updated: 2021-02-11T11:17:14Z embargo: 2019-11-02 file_id: '5942' file_name: Thesis_Steinrueck_final.pdf file_size: 7521973 relation: main_file file_date_updated: 2021-02-11T11:17:14Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '109' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '8029' pubrep_id: '1059' related_material: record: - id: '704' relation: part_of_dissertation status: public status: public supervisor: - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 title: The influence of sequence context on the evolution of bacterial gene expression type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2018' ... --- _id: '305' abstract: - lang: eng text: The hanging-drop network (HDN) is a technology platform based on a completely open microfluidic network at the bottom of an inverted, surface-patterned substrate. The platform is predominantly used for the formation, culturing, and interaction of self-assembled spherical microtissues (spheroids) under precisely controlled flow conditions. Here, we describe design, fabrication, and operation of microfluidic hanging-drop networks. acknowledgement: This work was financially supported by FP7 of the EU through the project “Body on a chip,” ICT-FET-296257, and the ERC Advanced Grant “NeuroCMOS” (contract 267351), as well as by an individual Ambizione Grant 142440 from the Swiss National Science Foundation for Olivier Frey. The research leading to these results also received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. [291734]. We would like to thank Alexander Stettler, ETH Zurich for his expertise and support in the cleanroom, and we acknowledge the Single Cell Unit of D-BSSE, ETH Zurich for assistance in microscopy issues. M.L. is grateful to the members of the Guet and Tkačik groups, IST Austria, for valuable comments and support. alternative_title: - MIMB author: - first_name: Patrick full_name: Misun, Patrick last_name: Misun - first_name: Axel full_name: Birchler, Axel last_name: Birchler - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Andreas full_name: Hierlemann, Andreas last_name: Hierlemann - first_name: Olivier full_name: Frey, Olivier last_name: Frey citation: ama: Misun P, Birchler A, Lang M, Hierlemann A, Frey O. Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. 2018;1771:183-202. doi:10.1007/978-1-4939-7792-5_15 apa: Misun, P., Birchler, A., Lang, M., Hierlemann, A., & Frey, O. (2018). Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. Springer. https://doi.org/10.1007/978-1-4939-7792-5_15 chicago: Misun, Patrick, Axel Birchler, Moritz Lang, Andreas Hierlemann, and Olivier Frey. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods in Molecular Biology. Springer, 2018. https://doi.org/10.1007/978-1-4939-7792-5_15. ieee: P. Misun, A. Birchler, M. Lang, A. Hierlemann, and O. Frey, “Fabrication and operation of microfluidic hanging drop networks,” Methods in Molecular Biology, vol. 1771. Springer, pp. 183–202, 2018. ista: Misun P, Birchler A, Lang M, Hierlemann A, Frey O. 2018. Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. 1771, 183–202. mla: Misun, Patrick, et al. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods in Molecular Biology, vol. 1771, Springer, 2018, pp. 183–202, doi:10.1007/978-1-4939-7792-5_15. short: P. Misun, A. Birchler, M. Lang, A. Hierlemann, O. Frey, Methods in Molecular Biology 1771 (2018) 183–202. date_created: 2018-12-11T11:45:43Z date_published: 2018-01-01T00:00:00Z date_updated: 2021-01-12T07:40:42Z day: '01' department: - _id: CaGu - _id: GaTk doi: 10.1007/978-1-4939-7792-5_15 ec_funded: 1 intvolume: ' 1771' language: - iso: eng month: '01' oa_version: None page: 183 - 202 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Methods in Molecular Biology publication_status: published publisher: Springer publist_id: '7574' quality_controlled: '1' scopus_import: 1 status: public title: Fabrication and operation of microfluidic hanging drop networks type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 1771 year: '2018' ... --- _id: '82' abstract: - lang: eng text: In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIRis maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIRin these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility—a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria—their “existence conditions.”. article_number: '2005971' article_processing_charge: Yes author: - first_name: Waqas full_name: Chaudhry, Waqas last_name: Chaudhry - first_name: Maros full_name: Pleska, Maros id: 4569785E-F248-11E8-B48F-1D18A9856A87 last_name: Pleska orcid: 0000-0001-7460-7479 - first_name: Nilang full_name: Shah, Nilang last_name: Shah - first_name: Howard full_name: Weiss, Howard last_name: Weiss - first_name: Ingrid full_name: Mccall, Ingrid last_name: Mccall - first_name: Justin full_name: Meyer, Justin last_name: Meyer - first_name: Animesh full_name: Gupta, Animesh last_name: Gupta - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Bruce full_name: Levin, Bruce last_name: Levin citation: ama: Chaudhry W, Pleska M, Shah N, et al. Leaky resistance and the conditions for the existence of lytic bacteriophage. PLoS Biology. 2018;16(8). doi:10.1371/journal.pbio.2005971 apa: Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin, B. (2018). Leaky resistance and the conditions for the existence of lytic bacteriophage. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.2005971 chicago: Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall, Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Leaky Resistance and the Conditions for the Existence of Lytic Bacteriophage.” PLoS Biology. Public Library of Science, 2018. https://doi.org/10.1371/journal.pbio.2005971. ieee: W. Chaudhry et al., “Leaky resistance and the conditions for the existence of lytic bacteriophage,” PLoS Biology, vol. 16, no. 8. Public Library of Science, 2018. ista: Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC, Levin B. 2018. Leaky resistance and the conditions for the existence of lytic bacteriophage. PLoS Biology. 16(8), 2005971. mla: Chaudhry, Waqas, et al. “Leaky Resistance and the Conditions for the Existence of Lytic Bacteriophage.” PLoS Biology, vol. 16, no. 8, 2005971, Public Library of Science, 2018, doi:10.1371/journal.pbio.2005971. short: W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta, C.C. Guet, B. Levin, PLoS Biology 16 (2018). date_created: 2018-12-11T11:44:32Z date_published: 2018-08-16T00:00:00Z date_updated: 2023-09-13T08:45:41Z day: '16' ddc: - '570' department: - _id: CaGu doi: 10.1371/journal.pbio.2005971 external_id: isi: - '000443383300024' file: - access_level: open_access checksum: 527076f78265cd4ea192cd1569851587 content_type: application/pdf creator: dernst date_created: 2018-12-17T12:55:31Z date_updated: 2020-07-14T12:48:10Z file_id: '5706' file_name: 2018_Plos_Chaudhry.pdf file_size: 4007095 relation: main_file file_date_updated: 2020-07-14T12:48:10Z has_accepted_license: '1' intvolume: ' 16' isi: 1 issue: '8' language: - iso: eng month: '08' oa: 1 oa_version: Published Version publication: PLoS Biology publication_status: published publisher: Public Library of Science publist_id: '7972' quality_controlled: '1' related_material: record: - id: '9810' relation: research_data status: public scopus_import: '1' status: public title: Leaky resistance and the conditions for the existence of lytic bacteriophage 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 16 year: '2018' ... --- _id: '19' abstract: - lang: eng text: Bacteria regulate genes to survive antibiotic stress, but regulation can be far from perfect. When regulation is not optimal, mutations that change gene expression can contribute to antibiotic resistance. It is not systematically understood to what extent natural gene regulation is or is not optimal for distinct antibiotics, and how changes in expression of specific genes quantitatively affect antibiotic resistance. Here we discover a simple quantitative relation between fitness, gene expression, and antibiotic potency, which rationalizes our observation that a multitude of genes and even innate antibiotic defense mechanisms have expression that is critically nonoptimal under antibiotic treatment. First, we developed a pooled-strain drug-diffusion assay and screened Escherichia coli overexpression and knockout libraries, finding that resistance to a range of 31 antibiotics could result from changing expression of a large and functionally diverse set of genes, in a primarily but not exclusively drug-specific manner. Second, by synthetically controlling the expression of single-drug and multidrug resistance genes, we observed that their fitness-expression functions changed dramatically under antibiotic treatment in accordance with a log-sensitivity relation. Thus, because many genes are nonoptimally expressed under antibiotic treatment, many regulatory mutations can contribute to resistance by altering expression and by activating latent defenses. article_processing_charge: No article_type: original author: - first_name: Adam full_name: Palmer, Adam last_name: Palmer - first_name: Remy P full_name: Chait, Remy P id: 3464AE84-F248-11E8-B48F-1D18A9856A87 last_name: Chait orcid: 0000-0003-0876-3187 - first_name: Roy full_name: Kishony, Roy last_name: Kishony citation: ama: Palmer A, Chait RP, Kishony R. Nonoptimal gene expression creates latent potential for antibiotic resistance. Molecular Biology and Evolution. 2018;35(11):2669-2684. doi:10.1093/molbev/msy163 apa: Palmer, A., Chait, R. P., & Kishony, R. (2018). Nonoptimal gene expression creates latent potential for antibiotic resistance. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msy163 chicago: Palmer, Adam, Remy P Chait, and Roy Kishony. “Nonoptimal Gene Expression Creates Latent Potential for Antibiotic Resistance.” Molecular Biology and Evolution. Oxford University Press, 2018. https://doi.org/10.1093/molbev/msy163. ieee: A. Palmer, R. P. Chait, and R. Kishony, “Nonoptimal gene expression creates latent potential for antibiotic resistance,” Molecular Biology and Evolution, vol. 35, no. 11. Oxford University Press, pp. 2669–2684, 2018. ista: Palmer A, Chait RP, Kishony R. 2018. Nonoptimal gene expression creates latent potential for antibiotic resistance. Molecular Biology and Evolution. 35(11), 2669–2684. mla: Palmer, Adam, et al. “Nonoptimal Gene Expression Creates Latent Potential for Antibiotic Resistance.” Molecular Biology and Evolution, vol. 35, no. 11, Oxford University Press, 2018, pp. 2669–84, doi:10.1093/molbev/msy163. short: A. Palmer, R.P. Chait, R. Kishony, Molecular Biology and Evolution 35 (2018) 2669–2684. date_created: 2018-12-11T11:44:11Z date_published: 2018-08-28T00:00:00Z date_updated: 2023-10-17T11:51:06Z day: '28' department: - _id: CaGu - _id: GaTk doi: 10.1093/molbev/msy163 external_id: isi: - '000452567200006' pmid: - '30169679' intvolume: ' 35' isi: 1 issue: '11' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pubmed/30169679 month: '08' oa: 1 oa_version: Submitted Version page: 2669 - 2684 pmid: 1 publication: Molecular Biology and Evolution publication_identifier: issn: - 0737-4038 publication_status: published publisher: Oxford University Press publist_id: '8036' quality_controlled: '1' scopus_import: '1' status: public title: Nonoptimal gene expression creates latent potential for antibiotic resistance type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 35 year: '2018' ... --- _id: '67' abstract: - lang: eng text: 'Gene regulatory networks evolve through rewiring of individual components—that is, through changes in regulatory connections. However, the mechanistic basis of regulatory rewiring is poorly understood. Using a canonical gene regulatory system, we quantify the properties of transcription factors that determine the evolutionary potential for rewiring of regulatory connections: robustness, tunability and evolvability. In vivo repression measurements of two repressors at mutated operator sites reveal their contrasting evolutionary potential: while robustness and evolvability were positively correlated, both were in trade-off with tunability. Epistatic interactions between adjacent operators alleviated this trade-off. A thermodynamic model explains how the differences in robustness, tunability and evolvability arise from biophysical characteristics of repressor–DNA binding. The model also uncovers that the energy matrix, which describes how mutations affect repressor–DNA binding, encodes crucial information about the evolutionary potential of a repressor. The biophysical determinants of evolutionary potential for regulatory rewiring constitute a mechanistic framework for understanding network evolution.' article_processing_charge: No article_type: original author: - first_name: Claudia full_name: Igler, Claudia id: 46613666-F248-11E8-B48F-1D18A9856A87 last_name: Igler - first_name: Mato full_name: Lagator, Mato id: 345D25EC-F248-11E8-B48F-1D18A9856A87 last_name: Lagator - first_name: Gasper full_name: Tkacik, Gasper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkacik orcid: 0000-0002-6699-1455 - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 citation: ama: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2018;2(10):1633-1643. doi:10.1038/s41559-018-0651-y apa: Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018). Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. Nature Publishing Group. https://doi.org/10.1038/s41559-018-0651-y chicago: Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Nature Ecology and Evolution. Nature Publishing Group, 2018. https://doi.org/10.1038/s41559-018-0651-y. ieee: C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary potential of transcription factors for gene regulatory rewiring,” Nature Ecology and Evolution, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018. ista: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2(10), 1633–1643. mla: Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Nature Ecology and Evolution, vol. 2, no. 10, Nature Publishing Group, 2018, pp. 1633–43, doi:10.1038/s41559-018-0651-y. short: C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology and Evolution 2 (2018) 1633–1643. date_created: 2018-12-11T11:44:27Z date_published: 2018-09-10T00:00:00Z date_updated: 2024-03-25T23:30:27Z day: '10' ddc: - '570' department: - _id: CaGu - _id: GaTk - _id: JoBo doi: 10.1038/s41559-018-0651-y ec_funded: 1 external_id: isi: - '000447947600021' file: - access_level: open_access checksum: 383a2e2c944a856e2e821ec8e7bf71b6 content_type: application/pdf creator: dernst date_created: 2020-05-14T11:28:52Z date_updated: 2020-07-14T12:47:37Z file_id: '7830' file_name: 2018_NatureEcology_Igler.pdf file_size: 1135973 relation: main_file file_date_updated: 2020-07-14T12:47:37Z has_accepted_license: '1' intvolume: ' 2' isi: 1 issue: '10' language: - iso: eng month: '09' oa: 1 oa_version: Submitted Version page: 1633 - 1643 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 2578D616-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '648440' name: Selective Barriers to Horizontal Gene Transfer - _id: 251EE76E-B435-11E9-9278-68D0E5697425 grant_number: '24573' name: Design principles underlying genetic switch architecture (DOC Fellowship) publication: Nature Ecology and Evolution publication_status: published publisher: Nature Publishing Group publist_id: '7987' quality_controlled: '1' related_material: record: - id: '5585' relation: popular_science status: public - id: '6371' relation: dissertation_contains status: public scopus_import: '1' status: public title: Evolutionary potential of transcription factors for gene regulatory rewiring type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 2 year: '2018' ...