--- _id: '457' abstract: - lang: eng text: Temperate bacteriophages integrate in bacterial genomes as prophages and represent an important source of genetic variation for bacterial evolution, frequently transmitting fitness-augmenting genes such as toxins responsible for virulence of major pathogens. However, only a fraction of bacteriophage infections are lysogenic and lead to prophage acquisition, whereas the majority are lytic and kill the infected bacteria. Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity to bacteriophages are expected to act as a double-edged sword and increase the odds of survival at the cost of depriving bacteria of potentially beneficial prophages. We show that although restriction-modification systems as mechanisms of innate immunity prevent both lytic and lysogenic infections indiscriminately in individual bacteria, they increase the number of prophage-acquiring individuals at the population level. We find that this counterintuitive result is a consequence of phage-host population dynamics, in which restriction-modification systems delay infection onset until bacteria reach densities at which the probability of lysogeny increases. These results underscore the importance of population-level dynamics as a key factor modulating costs and benefits of immunity to temperate bacteriophages article_processing_charge: No author: - first_name: Maros full_name: Pleska, Maros id: 4569785E-F248-11E8-B48F-1D18A9856A87 last_name: Pleska orcid: 0000-0001-7460-7479 - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Dominik full_name: Refardt, Dominik last_name: Refardt - first_name: Bruce full_name: Levin, Bruce last_name: Levin - 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: Pleska M, Lang M, Refardt D, Levin B, Guet CC. Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nature Ecology and Evolution. 2018;2(2):359-366. doi:10.1038/s41559-017-0424-z apa: Pleska, M., Lang, M., Refardt, D., Levin, B., & Guet, C. C. (2018). Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nature Ecology and Evolution. Springer Nature. https://doi.org/10.1038/s41559-017-0424-z chicago: Pleska, Maros, Moritz Lang, Dominik Refardt, Bruce Levin, and Calin C Guet. “Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with Innate Immunity.” Nature Ecology and Evolution. Springer Nature, 2018. https://doi.org/10.1038/s41559-017-0424-z. ieee: M. Pleska, M. Lang, D. Refardt, B. Levin, and C. C. Guet, “Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity,” Nature Ecology and Evolution, vol. 2, no. 2. Springer Nature, pp. 359–366, 2018. ista: Pleska M, Lang M, Refardt D, Levin B, Guet CC. 2018. Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nature Ecology and Evolution. 2(2), 359–366. mla: Pleska, Maros, et al. “Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with Innate Immunity.” Nature Ecology and Evolution, vol. 2, no. 2, Springer Nature, 2018, pp. 359–66, doi:10.1038/s41559-017-0424-z. short: M. Pleska, M. Lang, D. Refardt, B. Levin, C.C. Guet, Nature Ecology and Evolution 2 (2018) 359–366. date_created: 2018-12-11T11:46:35Z date_published: 2018-02-01T00:00:00Z date_updated: 2023-09-15T12:04:57Z day: '01' department: - _id: CaGu - _id: GaTk doi: 10.1038/s41559-017-0424-z ec_funded: 1 external_id: isi: - '000426516400027' intvolume: ' 2' isi: 1 issue: '2' language: - iso: eng month: '02' oa_version: None page: 359 - 366 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 251BCBEC-B435-11E9-9278-68D0E5697425 grant_number: RGY0079/2011 name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems (HFSP Young investigators' grant) - _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 (DOC Fellowship) publication: Nature Ecology and Evolution publication_status: published publisher: Springer Nature publist_id: '7364' quality_controlled: '1' related_material: record: - id: '202' relation: dissertation_contains status: public scopus_import: '1' status: public title: Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 2 year: '2018' ... --- _id: '5984' abstract: - lang: eng text: G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors. For the human pseudogene GPR33, we resurrect a signaling function that supports its hypothesized role as a pathogen entry site. These results demonstrate that substituting unknown chemical activators with a light switch can reveal information about protein function and provide an optically controlled protein library for exploring the physiology and therapeutic potential of understudied GPCRs. article_number: '1950' article_processing_charge: No author: - first_name: Maurizio full_name: Morri, Maurizio id: 4863116E-F248-11E8-B48F-1D18A9856A87 last_name: Morri - first_name: Inmaculada full_name: Sanchez-Romero, Inmaculada id: 3D9C5D30-F248-11E8-B48F-1D18A9856A87 last_name: Sanchez-Romero - first_name: Alexandra-Madelaine full_name: Tichy, Alexandra-Madelaine id: 29D8BB2C-F248-11E8-B48F-1D18A9856A87 last_name: Tichy - first_name: Stephanie full_name: Kainrath, Stephanie id: 32CFBA64-F248-11E8-B48F-1D18A9856A87 last_name: Kainrath - first_name: Elliot J. full_name: Gerrard, Elliot J. last_name: Gerrard - first_name: Priscila full_name: Hirschfeld, Priscila id: 435ACB3A-F248-11E8-B48F-1D18A9856A87 last_name: Hirschfeld - first_name: Jan full_name: Schwarz, Jan id: 346C1EC6-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Harald L full_name: Janovjak, Harald L id: 33BA6C30-F248-11E8-B48F-1D18A9856A87 last_name: Janovjak orcid: 0000-0002-8023-9315 citation: ama: Morri M, Sanchez-Romero I, Tichy A-M, et al. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 2018;9(1). doi:10.1038/s41467-018-04342-1 apa: Morri, M., Sanchez-Romero, I., Tichy, A.-M., Kainrath, S., Gerrard, E. J., Hirschfeld, P., … Janovjak, H. L. (2018). Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-018-04342-1 chicago: Morri, Maurizio, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J. Gerrard, Priscila Hirschfeld, Jan Schwarz, and Harald L Janovjak. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-04342-1. ieee: M. Morri et al., “Optical functionalization of human class A orphan G-protein-coupled receptors,” Nature Communications, vol. 9, no. 1. Springer Nature, 2018. ista: Morri M, Sanchez-Romero I, Tichy A-M, Kainrath S, Gerrard EJ, Hirschfeld P, Schwarz J, Janovjak HL. 2018. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 9(1), 1950. mla: Morri, Maurizio, et al. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” Nature Communications, vol. 9, no. 1, 1950, Springer Nature, 2018, doi:10.1038/s41467-018-04342-1. short: M. Morri, I. Sanchez-Romero, A.-M. Tichy, S. Kainrath, E.J. Gerrard, P. Hirschfeld, J. Schwarz, H.L. Janovjak, Nature Communications 9 (2018). date_created: 2019-02-14T10:50:24Z date_published: 2018-12-01T00:00:00Z date_updated: 2023-09-19T14:29:32Z day: '01' ddc: - '570' department: - _id: HaJa - _id: CaGu - _id: MiSi doi: 10.1038/s41467-018-04342-1 ec_funded: 1 external_id: isi: - '000432280000006' file: - access_level: open_access checksum: 8325fcc194264af4749e662a73bf66b5 content_type: application/pdf creator: kschuh date_created: 2019-02-14T10:58:29Z date_updated: 2020-07-14T12:47:14Z file_id: '5985' file_name: 2018_Springer_Morri.pdf file_size: 1349914 relation: main_file file_date_updated: 2020-07-14T12:47:14Z has_accepted_license: '1' intvolume: ' 9' isi: 1 issue: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version project: - _id: 25548C20-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '303564' name: Microbial Ion Channels for Synthetic Neurobiology - _id: 255A6082-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets publication: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Optical functionalization of human class A orphan G-protein-coupled receptors 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: 9 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: '438' abstract: - lang: eng text: The MazF toxin sequence-specifically cleaves single-stranded RNA upon various stressful conditions, and it is activated as a part of the mazEF toxin–antitoxin module in Escherichia coli. Although autoregulation of mazEF expression through the MazE antitoxin-dependent transcriptional repression has been biochemically characterized, less is known about post-transcriptional autoregulation, as well as how both of these autoregulatory features affect growth of single cells during conditions that promote MazF production. Here, we demonstrate post-transcriptional autoregulation of mazF expression dynamics by MazF cleaving its own transcript. Single-cell analyses of bacterial populations during ectopic MazF production indicated that two-level autoregulation of mazEF expression influences cell-to-cell growth rate heterogeneity. The increase in growth rate heterogeneity is governed by the MazE antitoxin, and tuned by the MazF-dependent mazF mRNA cleavage. Also, both autoregulatory features grant rapid exit from the stress caused by mazF overexpression. Time-lapse microscopy revealed that MazF-mediated cleavage of mazF mRNA leads to increased temporal variability in length of individual cells during ectopic mazF overexpression, as explained by a stochastic model indicating that mazEF mRNA cleavage underlies temporal fluctuations in MazF levels during stress. article_processing_charge: Yes (in subscription journal) author: - first_name: Nela full_name: Nikolic, Nela id: 42D9CABC-F248-11E8-B48F-1D18A9856A87 last_name: Nikolic orcid: 0000-0001-9068-6090 - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Alexandra full_name: Vandervelde, Alexandra last_name: Vandervelde - first_name: Tanino full_name: Albanese, Tanino last_name: Albanese - first_name: Lendert full_name: Gelens, Lendert last_name: Gelens - first_name: Isabella full_name: Moll, Isabella last_name: Moll citation: ama: Nikolic N, Bergmiller T, Vandervelde A, Albanese T, Gelens L, Moll I. Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations. Nucleic Acids Research. 2018;46(6):2918-2931. doi:10.1093/nar/gky079 apa: Nikolic, N., Bergmiller, T., Vandervelde, A., Albanese, T., Gelens, L., & Moll, I. (2018). Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations. Nucleic Acids Research. Oxford University Press. https://doi.org/10.1093/nar/gky079 chicago: Nikolic, Nela, Tobias Bergmiller, Alexandra Vandervelde, Tanino Albanese, Lendert Gelens, and Isabella Moll. “Autoregulation of MazEF Expression Underlies Growth Heterogeneity in Bacterial Populations.” Nucleic Acids Research. Oxford University Press, 2018. https://doi.org/10.1093/nar/gky079. ieee: N. Nikolic, T. Bergmiller, A. Vandervelde, T. Albanese, L. Gelens, and I. Moll, “Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations,” Nucleic Acids Research, vol. 46, no. 6. Oxford University Press, pp. 2918–2931, 2018. ista: Nikolic N, Bergmiller T, Vandervelde A, Albanese T, Gelens L, Moll I. 2018. Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations. Nucleic Acids Research. 46(6), 2918–2931. mla: Nikolic, Nela, et al. “Autoregulation of MazEF Expression Underlies Growth Heterogeneity in Bacterial Populations.” Nucleic Acids Research, vol. 46, no. 6, Oxford University Press, 2018, pp. 2918–31, doi:10.1093/nar/gky079. short: N. Nikolic, T. Bergmiller, A. Vandervelde, T. Albanese, L. Gelens, I. Moll, Nucleic Acids Research 46 (2018) 2918–2931. date_created: 2018-12-11T11:46:29Z date_published: 2018-04-06T00:00:00Z date_updated: 2024-02-21T13:44:45Z day: '06' ddc: - '576' department: - _id: CaGu doi: 10.1093/nar/gky079 external_id: isi: - '000429009500021' file: - access_level: open_access checksum: 3ff4f545c27e11a4cd20ccb30778793e content_type: application/pdf creator: system date_created: 2018-12-12T10:15:30Z date_updated: 2020-07-14T12:46:27Z file_id: '5151' file_name: IST-2018-971-v1+1_2018_Nikoloc_Autoregulation_of.pdf file_size: 5027978 relation: main_file file_date_updated: 2020-07-14T12:46:27Z has_accepted_license: '1' intvolume: ' 46' isi: 1 issue: '6' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: 2918-2931 project: - _id: 3AC91DDA-15DF-11EA-824D-93A3E7B544D1 call_identifier: FWF name: FWF Open Access Fund publication: Nucleic Acids Research publication_status: published publisher: Oxford University Press pubrep_id: '971' quality_controlled: '1' related_material: record: - id: '5569' relation: popular_science status: public scopus_import: '1' status: public title: Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 46 year: '2018' ... --- _id: '5569' abstract: - lang: eng text: "Nela Nikolic, Tobias Bergmiller, Alexandra Vandervelde, Tanino G. Albanese, Lendert Gelens, and Isabella Moll (2018)\r\n“Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations” Nucleic Acids Research, doi: 10.15479/AT:ISTA:74;\r\nmicroscopy experiments by Tobias Bergmiller; image and data analysis by Nela Nikolic." article_processing_charge: No author: - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Nela full_name: Nikolic, Nela id: 42D9CABC-F248-11E8-B48F-1D18A9856A87 last_name: Nikolic orcid: 0000-0001-9068-6090 citation: ama: Bergmiller T, Nikolic N. Time-lapse microscopy data. 2018. doi:10.15479/AT:ISTA:74 apa: Bergmiller, T., & Nikolic, N. (2018). Time-lapse microscopy data. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:74 chicago: Bergmiller, Tobias, and Nela Nikolic. “Time-Lapse Microscopy Data.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:74. ieee: T. Bergmiller and N. Nikolic, “Time-lapse microscopy data.” Institute of Science and Technology Austria, 2018. ista: Bergmiller T, Nikolic N. 2018. Time-lapse microscopy data, Institute of Science and Technology Austria, 10.15479/AT:ISTA:74. mla: Bergmiller, Tobias, and Nela Nikolic. Time-Lapse Microscopy Data. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:74. short: T. Bergmiller, N. Nikolic, (2018). datarep_id: '74' date_created: 2018-12-12T12:31:35Z date_published: 2018-02-07T00:00:00Z date_updated: 2024-02-21T13:44:45Z day: '07' ddc: - '579' department: - _id: CaGu doi: 10.15479/AT:ISTA:74 file: - access_level: open_access checksum: 61ebb92213cfffeba3ddbaff984b81af content_type: application/zip creator: system date_created: 2018-12-12T13:04:39Z date_updated: 2020-07-14T12:47:04Z file_id: '5637' file_name: IST-2018-74-v1+2_15-11-05.zip file_size: 3558703796 relation: main_file - access_level: open_access checksum: bf26649af310ef6892d68576515cde6d content_type: application/zip creator: system date_created: 2018-12-12T13:04:55Z date_updated: 2020-07-14T12:47:04Z file_id: '5638' file_name: IST-2018-74-v1+3_15-07-31.zip file_size: 1830422606 relation: main_file - access_level: open_access checksum: 8e46eedce06f22acb2be1a9b9d3f56bd content_type: application/zip creator: system date_created: 2018-12-12T13:05:11Z date_updated: 2020-07-14T12:47:04Z file_id: '5639' file_name: IST-2018-74-v1+4_Images_for_analysis.zip file_size: 2140849248 relation: main_file file_date_updated: 2020-07-14T12:47:04Z has_accepted_license: '1' keyword: - microscopy - microfluidics license: https://creativecommons.org/publicdomain/zero/1.0/ month: '02' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria publist_id: '7385' related_material: record: - id: '438' relation: research_paper status: public status: public title: Time-lapse microscopy data tmp: image: /images/cc_0.png legal_code_url: https://creativecommons.org/publicdomain/zero/1.0/legalcode name: Creative Commons Public Domain Dedication (CC0 1.0) short: CC0 (1.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2018' ... --- _id: '161' abstract: - lang: eng text: 'Which properties of metabolic networks can be derived solely from stoichiometry? Predictive results have been obtained by flux balance analysis (FBA), by postulating that cells set metabolic fluxes to maximize growth rate. Here we consider a generalization of FBA to single-cell level using maximum entropy modeling, which we extend and test experimentally. Specifically, we define for Escherichia coli metabolism a flux distribution that yields the experimental growth rate: the model, containing FBA as a limit, provides a better match to measured fluxes and it makes a wide range of predictions: on flux variability, regulation, and correlations; on the relative importance of stoichiometry vs. optimization; on scaling relations for growth rate distributions. We validate the latter here with single-cell data at different sub-inhibitory antibiotic concentrations. The model quantifies growth optimization as emerging from the interplay of competitive dynamics in the population and regulation of metabolism at the level of single cells.' article_number: '2988' article_processing_charge: No author: - first_name: Daniele full_name: De Martino, Daniele id: 3FF5848A-F248-11E8-B48F-1D18A9856A87 last_name: De Martino orcid: 0000-0002-5214-4706 - first_name: Andersson Anna full_name: Mc, Andersson Anna last_name: Mc - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - 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: Gasper full_name: Tkacik, Gasper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkacik orcid: 0000-0002-6699-1455 citation: ama: De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. Statistical mechanics for metabolic networks during steady state growth. Nature Communications. 2018;9(1). doi:10.1038/s41467-018-05417-9 apa: De Martino, D., Mc, A. A., Bergmiller, T., Guet, C. C., & Tkačik, G. (2018). Statistical mechanics for metabolic networks during steady state growth. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-018-05417-9 chicago: De Martino, Daniele, Andersson Anna Mc, Tobias Bergmiller, Calin C Guet, and Gašper Tkačik. “Statistical Mechanics for Metabolic Networks during Steady State Growth.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-05417-9. ieee: D. De Martino, A. A. Mc, T. Bergmiller, C. C. Guet, and G. Tkačik, “Statistical mechanics for metabolic networks during steady state growth,” Nature Communications, vol. 9, no. 1. Springer Nature, 2018. ista: De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. 2018. Statistical mechanics for metabolic networks during steady state growth. Nature Communications. 9(1), 2988. mla: De Martino, Daniele, et al. “Statistical Mechanics for Metabolic Networks during Steady State Growth.” Nature Communications, vol. 9, no. 1, 2988, Springer Nature, 2018, doi:10.1038/s41467-018-05417-9. short: D. De Martino, A.A. Mc, T. Bergmiller, C.C. Guet, G. Tkačik, Nature Communications 9 (2018). date_created: 2018-12-11T11:44:57Z date_published: 2018-07-30T00:00:00Z date_updated: 2024-02-21T13:45:39Z day: '30' ddc: - '570' department: - _id: GaTk - _id: CaGu doi: 10.1038/s41467-018-05417-9 ec_funded: 1 external_id: isi: - '000440149300021' file: - access_level: open_access checksum: 3ba7ab27b27723c7dcf633e8fc1f8f18 content_type: application/pdf creator: dernst date_created: 2018-12-17T16:44:28Z date_updated: 2020-07-14T12:45:06Z file_id: '5728' file_name: 2018_NatureComm_DeMartino.pdf file_size: 1043205 relation: main_file file_date_updated: 2020-07-14T12:45:06Z has_accepted_license: '1' intvolume: ' 9' isi: 1 issue: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Nature Communications publication_status: published publisher: Springer Nature publist_id: '7760' quality_controlled: '1' related_material: record: - id: '5587' relation: popular_science status: public scopus_import: '1' status: public title: Statistical mechanics for metabolic networks during steady state growth 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: 9 year: '2018' ... --- _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: '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: 2024-03-28T23:30:49Z 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' ... --- _id: '5585' abstract: - lang: eng text: Mean repression values and standard error of the mean are given for all operator mutant libraries. article_processing_charge: No 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. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. 2018. doi:10.15479/AT:ISTA:108 apa: Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018). Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:108 chicago: Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:108. ieee: C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring.” Institute of Science and Technology Austria, 2018. ista: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring, Institute of Science and Technology Austria, 10.15479/AT:ISTA:108. mla: Igler, Claudia, et al. Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:108. short: C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, (2018). datarep_id: '108' date_created: 2018-12-12T12:31:40Z date_published: 2018-07-20T00:00:00Z date_updated: 2024-03-28T23:30:49Z day: '20' ddc: - '576' department: - _id: CaGu - _id: GaTk doi: 10.15479/AT:ISTA:108 ec_funded: 1 file: - access_level: open_access checksum: 1435781526c77413802adee0d4583cce content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet creator: system date_created: 2018-12-12T13:02:45Z date_updated: 2020-07-14T12:47:07Z file_id: '5611' file_name: IST-2018-108-v1+1_data_figures.xlsx file_size: 16507 relation: main_file file_date_updated: 2020-07-14T12:47:07Z has_accepted_license: '1' month: '07' oa: 1 oa_version: Published Version 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) publisher: Institute of Science and Technology Austria related_material: record: - id: '67' relation: research_paper status: public - id: '6371' relation: research_paper status: public status: public title: Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring tmp: image: /images/cc_0.png legal_code_url: https://creativecommons.org/publicdomain/zero/1.0/legalcode name: Creative Commons Public Domain Dedication (CC0 1.0) short: CC0 (1.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2018' ... --- _id: '538' abstract: - lang: ger text: 'Optogenetik und Photopharmakologie ermöglichen präzise räumliche und zeitliche Kontrolle von Proteinwechselwirkung und -funktion in Zellen und Tieren. Optogenetische Methoden, die auf grünes Licht ansprechen und zum Trennen von Proteinkomplexen geeignet sind, sind nichtweitläufig verfügbar, würden jedoch mehrfarbige Experimente zur Beantwortung von biologischen Fragestellungen ermöglichen. Hier demonstrieren wir die Verwendung von Cobalamin(Vitamin B12)-bindenden Domänen von bakteriellen CarH-Transkriptionsfaktoren zur Grünlicht-induzierten Dissoziation von Rezeptoren. Fusioniert mit dem Fibroblasten-W achstumsfaktor-Rezeptor 1 führten diese im Dunkeln in kultivierten Zellen zu Signalaktivität durch Oligomerisierung, welche durch Beleuchten umgehend aufgehoben wurde. In Zebrafischembryonen, die einen derartigen Rezeptor exprimieren, ermöglichte grünes Licht die Kontrolle über abnormale Signalaktivität während der Embryonalentwicklung. ' author: - first_name: Stephanie full_name: Kainrath, Stephanie id: 32CFBA64-F248-11E8-B48F-1D18A9856A87 last_name: Kainrath - first_name: Manuela full_name: Stadler, Manuela last_name: Stadler - first_name: Eva full_name: Gschaider-Reichhart, Eva id: 3FEE232A-F248-11E8-B48F-1D18A9856A87 last_name: Gschaider-Reichhart orcid: 0000-0002-7218-7738 - first_name: Martin full_name: Distel, Martin last_name: Distel - first_name: Harald L full_name: Janovjak, Harald L id: 33BA6C30-F248-11E8-B48F-1D18A9856A87 last_name: Janovjak orcid: 0000-0002-8023-9315 citation: ama: Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte Chemie. 2017;129(16):4679-4682. doi:10.1002/ange.201611998 apa: Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., & Janovjak, H. L. (2017). Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte Chemie. Wiley. https://doi.org/10.1002/ange.201611998 chicago: Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel, and Harald L Janovjak. “Grünlicht-Induzierte Rezeptorinaktivierung Durch Cobalamin-Bindende Domänen.” Angewandte Chemie. Wiley, 2017. https://doi.org/10.1002/ange.201611998. ieee: S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak, “Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen,” Angewandte Chemie, vol. 129, no. 16. Wiley, pp. 4679–4682, 2017. ista: Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017. Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte Chemie. 129(16), 4679–4682. mla: Kainrath, Stephanie, et al. “Grünlicht-Induzierte Rezeptorinaktivierung Durch Cobalamin-Bindende Domänen.” Angewandte Chemie, vol. 129, no. 16, Wiley, 2017, pp. 4679–82, doi:10.1002/ange.201611998. short: S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak, Angewandte Chemie 129 (2017) 4679–4682. date_created: 2018-12-11T11:47:02Z date_published: 2017-05-20T00:00:00Z date_updated: 2021-01-12T08:01:33Z day: '20' ddc: - '571' department: - _id: CaGu - _id: HaJa doi: 10.1002/ange.201611998 ec_funded: 1 file: - access_level: open_access checksum: d66fee867e7cdbfa3fe276c2fb0778bb content_type: application/pdf creator: system date_created: 2018-12-12T10:13:24Z date_updated: 2020-07-14T12:46:39Z file_id: '5007' file_name: IST-2018-932-v1+1_Kainrath_et_al-2017-Angewandte_Chemie.pdf file_size: 1668557 relation: main_file file_date_updated: 2020-07-14T12:46:39Z has_accepted_license: '1' intvolume: ' 129' issue: '16' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: 4679 - 4682 project: - _id: 25548C20-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '303564' name: Microbial Ion Channels for Synthetic Neurobiology - _id: 255A6082-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets publication: Angewandte Chemie publication_status: published publisher: Wiley publist_id: '7279' pubrep_id: '932' quality_controlled: '1' status: public title: Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 129 year: '2017' ...