--- _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 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' ... --- _id: '570' abstract: - lang: eng text: 'Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution. ' article_number: e28921 author: - first_name: Mato full_name: Lagator, Mato id: 345D25EC-F248-11E8-B48F-1D18A9856A87 last_name: Lagator - first_name: Srdjan full_name: Sarikas, Srdjan id: 35F0286E-F248-11E8-B48F-1D18A9856A87 last_name: Sarikas - first_name: Hande full_name: Acar, Hande id: 2DDF136A-F248-11E8-B48F-1D18A9856A87 last_name: Acar orcid: 0000-0003-1986-9753 - 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: Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 2017;6. doi:10.7554/eLife.28921 apa: Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., & Guet, C. C. (2017). Regulatory network structure determines patterns of intermolecular epistasis. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.28921 chicago: Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.28921. ieee: M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory network structure determines patterns of intermolecular epistasis,” eLife, vol. 6. eLife Sciences Publications, 2017. ista: Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921. mla: Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife, vol. 6, e28921, eLife Sciences Publications, 2017, doi:10.7554/eLife.28921. short: M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017). date_created: 2018-12-11T11:47:14Z date_published: 2017-11-13T00:00:00Z date_updated: 2021-01-12T08:03:15Z day: '13' ddc: - '576' department: - _id: CaGu - _id: JoBo - _id: NiBa doi: 10.7554/eLife.28921 ec_funded: 1 file: - access_level: open_access checksum: 273ab17f33305e4eaafd911ff88e7c5b content_type: application/pdf creator: system date_created: 2018-12-12T10:14:42Z date_updated: 2020-07-14T12:47:10Z file_id: '5096' file_name: IST-2017-918-v1+1_elife-28921-figures-v3.pdf file_size: 8453470 relation: main_file - access_level: open_access checksum: b433f90576c7be597cd43367946f8e7f content_type: application/pdf creator: system date_created: 2018-12-12T10:14:43Z date_updated: 2020-07-14T12:47:10Z file_id: '5097' file_name: IST-2017-918-v1+2_elife-28921-v3.pdf file_size: 1953221 relation: main_file file_date_updated: 2020-07-14T12:47:10Z has_accepted_license: '1' intvolume: ' 6' language: - iso: eng month: '11' 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 publication: eLife publication_identifier: issn: - 2050084X publication_status: published publisher: eLife Sciences Publications publist_id: '7244' pubrep_id: '918' quality_controlled: '1' scopus_import: 1 status: public title: Regulatory network structure determines patterns of intermolecular epistasis 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: 6 year: '2017' ... --- _id: '613' abstract: - lang: eng text: 'Bacteria in groups vary individually, and interact with other bacteria and the environment to produce population-level patterns of gene expression. Investigating such behavior in detail requires measuring and controlling populations at the single-cell level alongside precisely specified interactions and environmental characteristics. Here we present an automated, programmable platform that combines image-based gene expression and growth measurements with on-line optogenetic expression control for hundreds of individual Escherichia coli cells over days, in a dynamically adjustable environment. This integrated platform broadly enables experiments that bridge individual and population behaviors. We demonstrate: (i) population structuring by independent closed-loop control of gene expression in many individual cells, (ii) cell-cell variation control during antibiotic perturbation, (iii) hybrid bio-digital circuits in single cells, and freely specifiable digital communication between individual bacteria. These examples showcase the potential for real-time integration of theoretical models with measurement and control of many individual cells to investigate and engineer microbial population behavior.' acknowledgement: We are grateful to M. Lang, H. Janovjak, M. Khammash, A. Milias-Argeitis, M. Rullan, G. Batt, A. Bosma-Moody, Aryan, S. Leibler, and members of the Guet and Tkačik groups for helpful discussion, comments, and suggestions. We thank A. Moglich, T. Mathes, J. Tabor, and S. Schmidl for kind gifts of strains, and R. Hauschild, B. Knep, M. Lang, T. Asenov, E. Papusheva, T. Menner, T. Adletzberger, and J. Merrin for technical assistance. The research leading to these results has 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]. (to R.C. and J.R.), Austrian Science Fund grant FWF P28844 (to G.T.), and internal IST Austria Interdisciplinary Project Support. J.R. acknowledges support from the Agence Nationale de la Recherche (ANR) under Grant Nos. ANR-16-CE33-0018 (MEMIP), ANR-16-CE12-0025 (COGEX) and ANR-10-BINF-06-01 (ICEBERG). article_number: '1535' article_processing_charge: Yes (in subscription journal) author: - 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: Jakob full_name: Ruess, Jakob id: 4A245D00-F248-11E8-B48F-1D18A9856A87 last_name: Ruess orcid: 0000-0003-1615-3282 - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Gasper full_name: Tkacik, Gasper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkacik 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: Chait RP, Ruess J, Bergmiller T, Tkačik G, Guet CC. Shaping bacterial population behavior through computer interfaced control of individual cells. Nature Communications. 2017;8(1). doi:10.1038/s41467-017-01683-1 apa: Chait, R. P., Ruess, J., Bergmiller, T., Tkačik, G., & Guet, C. C. (2017). Shaping bacterial population behavior through computer interfaced control of individual cells. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-017-01683-1 chicago: Chait, Remy P, Jakob Ruess, Tobias Bergmiller, Gašper Tkačik, and Calin C Guet. “Shaping Bacterial Population Behavior through Computer Interfaced Control of Individual Cells.” Nature Communications. Nature Publishing Group, 2017. https://doi.org/10.1038/s41467-017-01683-1. ieee: R. P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, and C. C. Guet, “Shaping bacterial population behavior through computer interfaced control of individual cells,” Nature Communications, vol. 8, no. 1. Nature Publishing Group, 2017. ista: Chait RP, Ruess J, Bergmiller T, Tkačik G, Guet CC. 2017. Shaping bacterial population behavior through computer interfaced control of individual cells. Nature Communications. 8(1), 1535. mla: Chait, Remy P., et al. “Shaping Bacterial Population Behavior through Computer Interfaced Control of Individual Cells.” Nature Communications, vol. 8, no. 1, 1535, Nature Publishing Group, 2017, doi:10.1038/s41467-017-01683-1. short: R.P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, C.C. Guet, Nature Communications 8 (2017). date_created: 2018-12-11T11:47:30Z date_published: 2017-12-01T00:00:00Z date_updated: 2021-01-12T08:06:15Z day: '01' ddc: - '576' - '579' department: - _id: CaGu - _id: GaTk doi: 10.1038/s41467-017-01683-1 ec_funded: 1 file: - access_level: open_access checksum: 44bb5d0229926c23a9955d9fe0f9723f content_type: application/pdf creator: system date_created: 2018-12-12T10:16:05Z date_updated: 2020-07-14T12:47:20Z file_id: '5190' file_name: IST-2017-911-v1+1_s41467-017-01683-1.pdf file_size: 1951699 relation: main_file file_date_updated: 2020-07-14T12:47:20Z has_accepted_license: '1' intvolume: ' 8' issue: '1' language: - iso: eng month: '12' 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: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: Nature Communications publication_identifier: issn: - '20411723' publication_status: published publisher: Nature Publishing Group publist_id: '7191' pubrep_id: '911' quality_controlled: '1' scopus_import: 1 status: public title: Shaping bacterial population behavior through computer interfaced control of individual 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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 8 year: '2017' ... --- _id: '624' abstract: - lang: eng text: Bacteria adapt to adverse environmental conditions by altering gene expression patterns. Recently, a novel stress adaptation mechanism has been described that allows Escherichia coli to alter gene expression at the post-transcriptional level. The key player in this regulatory pathway is the endoribonuclease MazF, the toxin component of the toxin-antitoxin module mazEF that is triggered by various stressful conditions. In general, MazF degrades the majority of transcripts by cleaving at ACA sites, which results in the retardation of bacterial growth. Furthermore, MazF can process a small subset of mRNAs and render them leaderless by removing their ribosome binding site. MazF concomitantly modifies ribosomes, making them selective for the translation of leaderless mRNAs. In this study, we employed fluorescent reporter-systems to investigate mazEF expression during stressful conditions, and to infer consequences of the mRNA processing mediated by MazF on gene expression at the single-cell level. Our results suggest that mazEF transcription is maintained at low levels in single cells encountering adverse conditions, such as antibiotic stress or amino acid starvation. Moreover, using the grcA mRNA as a model for MazF-mediated mRNA processing, we found that MazF activation promotes heterogeneity in the grcA reporter expression, resulting in a subpopulation of cells with increased levels of GrcA reporter protein. acknowledgement: 'Austrian Science Fund (FWF): M1697, P22249; Swiss National Science Foundation (SNF): 145706; European Commission;FWF Special Research Program: RNA-REG F43' article_number: '3830' author: - first_name: Nela full_name: Nikolic, Nela id: 42D9CABC-F248-11E8-B48F-1D18A9856A87 last_name: Nikolic orcid: 0000-0001-9068-6090 - first_name: Zrinka full_name: Didara, Zrinka last_name: Didara - first_name: Isabella full_name: Moll, Isabella last_name: Moll citation: ama: Nikolic N, Didara Z, Moll I. MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. PeerJ. 2017;2017(9). doi:10.7717/peerj.3830 apa: Nikolic, N., Didara, Z., & Moll, I. (2017). MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. PeerJ. PeerJ. https://doi.org/10.7717/peerj.3830 chicago: Nikolic, Nela, Zrinka Didara, and Isabella Moll. “MazF Activation Promotes Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.” PeerJ. PeerJ, 2017. https://doi.org/10.7717/peerj.3830. ieee: N. Nikolic, Z. Didara, and I. Moll, “MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations,” PeerJ, vol. 2017, no. 9. PeerJ, 2017. ista: Nikolic N, Didara Z, Moll I. 2017. MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. PeerJ. 2017(9), 3830. mla: Nikolic, Nela, et al. “MazF Activation Promotes Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.” PeerJ, vol. 2017, no. 9, 3830, PeerJ, 2017, doi:10.7717/peerj.3830. short: N. Nikolic, Z. Didara, I. Moll, PeerJ 2017 (2017). date_created: 2018-12-11T11:47:33Z date_published: 2017-09-21T00:00:00Z date_updated: 2021-01-12T08:06:48Z day: '21' ddc: - '579' department: - _id: CaGu doi: 10.7717/peerj.3830 file: - access_level: open_access checksum: 3d79ae6b6eabc90b0eaaed82ff3493b0 content_type: application/pdf creator: system date_created: 2018-12-12T10:11:51Z date_updated: 2020-07-14T12:47:24Z file_id: '4908' file_name: IST-2017-909-v1+1_peerj-3830.pdf file_size: 682064 relation: main_file file_date_updated: 2020-07-14T12:47:24Z has_accepted_license: '1' intvolume: ' 2017' issue: '9' language: - iso: eng month: '09' oa: 1 oa_version: Published Version publication: PeerJ publication_identifier: issn: - '21678359' publication_status: published publisher: PeerJ publist_id: '7172' pubrep_id: '909' quality_controlled: '1' scopus_import: 1 status: public title: MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 2017 year: '2017' ... --- _id: '655' abstract: - lang: eng text: 'The bacterial flagellum is a self-assembling nanomachine. The external flagellar filament, several times longer than a bacterial cell body, is made of a few tens of thousands subunits of a single protein: flagellin. A fundamental problem concerns the molecular mechanism of how the flagellum grows outside the cell, where no discernible energy source is available. Here, we monitored the dynamic assembly of individual flagella using in situ labelling and real-time immunostaining of elongating flagellar filaments. We report that the rate of flagellum growth, initially ~1,700 amino acids per second, decreases with length and that the previously proposed chain mechanism does not contribute to the filament elongation dynamics. Inhibition of the proton motive force-dependent export apparatus revealed a major contribution of substrate injection in driving filament elongation. The combination of experimental and mathematical evidence demonstrates that a simple, injection-diffusion mechanism controls bacterial flagella growth outside the cell.' article_number: e23136 author: - first_name: Thibaud full_name: Renault, Thibaud last_name: Renault - first_name: Anthony full_name: Abraham, Anthony last_name: Abraham - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Guillaume full_name: Paradis, Guillaume last_name: Paradis - first_name: Simon full_name: Rainville, Simon last_name: Rainville - first_name: Emmanuelle full_name: Charpentier, Emmanuelle last_name: Charpentier - 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: Yuhai full_name: Tu, Yuhai last_name: Tu - first_name: Keiichi full_name: Namba, Keiichi last_name: Namba - first_name: James full_name: Keener, James last_name: Keener - first_name: Tohru full_name: Minamino, Tohru last_name: Minamino - first_name: Marc full_name: Erhardt, Marc last_name: Erhardt citation: ama: Renault T, Abraham A, Bergmiller T, et al. Bacterial flagella grow through an injection diffusion mechanism. eLife. 2017;6. doi:10.7554/eLife.23136 apa: Renault, T., Abraham, A., Bergmiller, T., Paradis, G., Rainville, S., Charpentier, E., … Erhardt, M. (2017). Bacterial flagella grow through an injection diffusion mechanism. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.23136 chicago: Renault, Thibaud, Anthony Abraham, Tobias Bergmiller, Guillaume Paradis, Simon Rainville, Emmanuelle Charpentier, Calin C Guet, et al. “Bacterial Flagella Grow through an Injection Diffusion Mechanism.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.23136. ieee: T. Renault et al., “Bacterial flagella grow through an injection diffusion mechanism,” eLife, vol. 6. eLife Sciences Publications, 2017. ista: Renault T, Abraham A, Bergmiller T, Paradis G, Rainville S, Charpentier E, Guet CC, Tu Y, Namba K, Keener J, Minamino T, Erhardt M. 2017. Bacterial flagella grow through an injection diffusion mechanism. eLife. 6, e23136. mla: Renault, Thibaud, et al. “Bacterial Flagella Grow through an Injection Diffusion Mechanism.” ELife, vol. 6, e23136, eLife Sciences Publications, 2017, doi:10.7554/eLife.23136. short: T. Renault, A. Abraham, T. Bergmiller, G. Paradis, S. Rainville, E. Charpentier, C.C. Guet, Y. Tu, K. Namba, J. Keener, T. Minamino, M. Erhardt, ELife 6 (2017). date_created: 2018-12-11T11:47:44Z date_published: 2017-03-06T00:00:00Z date_updated: 2021-01-12T08:07:55Z day: '06' ddc: - '579' department: - _id: CaGu doi: 10.7554/eLife.23136 file: - access_level: open_access checksum: 39e1c3e82ddac83a30422fa72fa1a383 content_type: application/pdf creator: system date_created: 2018-12-12T10:08:53Z date_updated: 2020-07-14T12:47:33Z file_id: '4716' file_name: IST-2017-904-v1+1_elife-23136-v2.pdf file_size: 5520359 relation: main_file - access_level: open_access checksum: a6d542253028f52e00aa29739ddffe8f content_type: application/pdf creator: system date_created: 2018-12-12T10:08:54Z date_updated: 2020-07-14T12:47:33Z file_id: '4717' file_name: IST-2017-904-v1+2_elife-23136-figures-v2.pdf file_size: 11242920 relation: main_file file_date_updated: 2020-07-14T12:47:33Z has_accepted_license: '1' intvolume: ' 6' language: - iso: eng month: '03' oa: 1 oa_version: Published Version publication: eLife publication_identifier: issn: - 2050084X publication_status: published publisher: eLife Sciences Publications publist_id: '7082' pubrep_id: '904' quality_controlled: '1' scopus_import: 1 status: public title: Bacterial flagella grow through an injection diffusion mechanism 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: 6 year: '2017' ... --- _id: '541' abstract: - lang: eng text: 'While we have good understanding of bacterial metabolism at the population level, we know little about the metabolic behavior of individual cells: do single cells in clonal populations sometimes specialize on different metabolic pathways? Such metabolic specialization could be driven by stochastic gene expression and could provide individual cells with growth benefits of specialization. We measured the degree of phenotypic specialization in two parallel metabolic pathways, the assimilation of glucose and arabinose. We grew Escherichia coli in chemostats, and used isotope-labeled sugars in combination with nanometer-scale secondary ion mass spectrometry and mathematical modeling to quantify sugar assimilation at the single-cell level. We found large variation in metabolic activities between single cells, both in absolute assimilation and in the degree to which individual cells specialize in the assimilation of different sugars. Analysis of transcriptional reporters indicated that this variation was at least partially based on cell-to-cell variation in gene expression. Metabolic differences between cells in clonal populations could potentially reduce metabolic incompatibilities between different pathways, and increase the rate at which parallel reactions can be performed.' article_number: e1007122 author: - first_name: Nela full_name: Nikolic, Nela id: 42D9CABC-F248-11E8-B48F-1D18A9856A87 last_name: Nikolic orcid: 0000-0001-9068-6090 - first_name: Frank full_name: Schreiber, Frank last_name: Schreiber - first_name: Alma full_name: Dal Co, Alma last_name: Dal Co - first_name: Daniel full_name: Kiviet, Daniel last_name: Kiviet - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Sten full_name: Littmann, Sten last_name: Littmann - first_name: Marcel full_name: Kuypers, Marcel last_name: Kuypers - first_name: Martin full_name: Ackermann, Martin last_name: Ackermann citation: ama: Nikolic N, Schreiber F, Dal Co A, et al. Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations. PLoS Genetics. 2017;13(12). doi:10.1371/journal.pgen.1007122 apa: Nikolic, N., Schreiber, F., Dal Co, A., Kiviet, D., Bergmiller, T., Littmann, S., … Ackermann, M. (2017). Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1007122 chicago: Nikolic, Nela, Frank Schreiber, Alma Dal Co, Daniel Kiviet, Tobias Bergmiller, Sten Littmann, Marcel Kuypers, and Martin Ackermann. “Cell-to-Cell Variation and Specialization in Sugar Metabolism in Clonal Bacterial Populations.” PLoS Genetics. Public Library of Science, 2017. https://doi.org/10.1371/journal.pgen.1007122. ieee: N. Nikolic et al., “Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations,” PLoS Genetics, vol. 13, no. 12. Public Library of Science, 2017. ista: Nikolic N, Schreiber F, Dal Co A, Kiviet D, Bergmiller T, Littmann S, Kuypers M, Ackermann M. 2017. Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations. PLoS Genetics. 13(12), e1007122. mla: Nikolic, Nela, et al. “Cell-to-Cell Variation and Specialization in Sugar Metabolism in Clonal Bacterial Populations.” PLoS Genetics, vol. 13, no. 12, e1007122, Public Library of Science, 2017, doi:10.1371/journal.pgen.1007122. short: N. Nikolic, F. Schreiber, A. Dal Co, D. Kiviet, T. Bergmiller, S. Littmann, M. Kuypers, M. Ackermann, PLoS Genetics 13 (2017). date_created: 2018-12-11T11:47:04Z date_published: 2017-12-18T00:00:00Z date_updated: 2023-02-23T14:10:34Z day: '18' ddc: - '576' - '579' department: - _id: CaGu doi: 10.1371/journal.pgen.1007122 ec_funded: 1 file: - access_level: open_access checksum: 22426d9382f21554bad5fa5967afcfd0 content_type: application/pdf creator: system date_created: 2018-12-12T10:14:35Z date_updated: 2020-07-14T12:46:46Z file_id: '5088' file_name: IST-2018-959-v1+1_2017_Nikolic_Cell-to-cell.pdf file_size: 1308475 relation: main_file file_date_updated: 2020-07-14T12:46:46Z has_accepted_license: '1' intvolume: ' 13' issue: '12' language: - iso: eng month: '12' 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 publication: PLoS Genetics publication_identifier: issn: - '15537390' publication_status: published publisher: Public Library of Science publist_id: '7275' pubrep_id: '959' quality_controlled: '1' related_material: record: - id: '9844' relation: research_data status: public - id: '9845' relation: research_data status: public - id: '9846' relation: research_data status: public scopus_import: 1 status: public title: Cell-to-cell variation and specialization in sugar metabolism in clonal 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 13 year: '2017' ... --- _id: '9847' abstract: - lang: eng text: information on culture conditions, phage mutagenesis, verification and lysate preparation; Raw data 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: 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, Guet CC. Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification. 2017. doi:10.6084/m9.figshare.5633917.v1 apa: Pleska, M., & Guet, C. C. (2017). Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification. The Royal Society. https://doi.org/10.6084/m9.figshare.5633917.v1 chicago: Pleska, Maros, and Calin C Guet. “Supplementary Materials and Methods; Full Data Set from Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” The Royal Society, 2017. https://doi.org/10.6084/m9.figshare.5633917.v1. ieee: M. Pleska and C. C. Guet, “Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification.” The Royal Society, 2017. ista: Pleska M, Guet CC. 2017. Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification, The Royal Society, 10.6084/m9.figshare.5633917.v1. mla: Pleska, Maros, and Calin C. Guet. Supplementary Materials and Methods; Full Data Set from Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification. The Royal Society, 2017, doi:10.6084/m9.figshare.5633917.v1. short: M. Pleska, C.C. Guet, (2017). date_created: 2021-08-09T13:54:38Z date_published: 2017-11-27T00:00:00Z date_updated: 2023-02-23T12:29:44Z day: '27' department: - _id: CaGu doi: 10.6084/m9.figshare.5633917.v1 main_file_link: - open_access: '1' url: https://doi.org/10.6084/m9.figshare.5633917.v1 month: '11' oa: 1 oa_version: Published Version publisher: The Royal Society related_material: record: - id: '561' relation: used_in_publication status: public status: public title: Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2017' ... --- _id: '9845' abstract: - lang: eng text: "Estimates of 13 C-arabinose and 2 H-glucose uptake from the fractions of heavy isotopes measured\tin single cells" article_processing_charge: No author: - first_name: Nela full_name: Nikolic, Nela id: 42D9CABC-F248-11E8-B48F-1D18A9856A87 last_name: Nikolic orcid: 0000-0001-9068-6090 - first_name: Frank full_name: Schreiber, Frank last_name: Schreiber - first_name: Alma full_name: Dal Co, Alma last_name: Dal Co - first_name: Daniel full_name: Kiviet, Daniel last_name: Kiviet - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Sten full_name: Littmann, Sten last_name: Littmann - first_name: Marcel full_name: Kuypers, Marcel last_name: Kuypers - first_name: Martin full_name: Ackermann, Martin last_name: Ackermann citation: ama: Nikolic N, Schreiber F, Dal Co A, et al. Mathematical model. 2017. doi:10.1371/journal.pgen.1007122.s017 apa: Nikolic, N., Schreiber, F., Dal Co, A., Kiviet, D., Bergmiller, T., Littmann, S., … Ackermann, M. (2017). Mathematical model. Public Library of Science. https://doi.org/10.1371/journal.pgen.1007122.s017 chicago: Nikolic, Nela, Frank Schreiber, Alma Dal Co, Daniel Kiviet, Tobias Bergmiller, Sten Littmann, Marcel Kuypers, and Martin Ackermann. “Mathematical Model.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pgen.1007122.s017. ieee: N. Nikolic et al., “Mathematical model.” Public Library of Science, 2017. ista: Nikolic N, Schreiber F, Dal Co A, Kiviet D, Bergmiller T, Littmann S, Kuypers M, Ackermann M. 2017. Mathematical model, Public Library of Science, 10.1371/journal.pgen.1007122.s017. mla: Nikolic, Nela, et al. Mathematical Model. Public Library of Science, 2017, doi:10.1371/journal.pgen.1007122.s017. short: N. Nikolic, F. Schreiber, A. Dal Co, D. Kiviet, T. Bergmiller, S. Littmann, M. Kuypers, M. Ackermann, (2017). date_created: 2021-08-09T13:31:51Z date_published: 2017-12-18T00:00:00Z date_updated: 2023-02-23T12:25:04Z day: '18' department: - _id: CaGu doi: 10.1371/journal.pgen.1007122.s017 month: '12' oa_version: None publisher: Public Library of Science related_material: record: - id: '541' relation: used_in_publication status: public status: public title: Mathematical model type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2017' ... --- _id: '9849' abstract: - lang: eng text: This text provides additional information about the model, a derivation of the analytic results in Eq (4), and details about simulations of an additional parameter set. article_processing_charge: No author: - first_name: Marta full_name: Lukacisinova, Marta id: 4342E402-F248-11E8-B48F-1D18A9856A87 last_name: Lukacisinova orcid: 0000-0002-2519-8004 - first_name: Sebastian full_name: Novak, Sebastian id: 461468AE-F248-11E8-B48F-1D18A9856A87 last_name: Novak - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 citation: ama: Lukacisinova M, Novak S, Paixao T. Modelling and simulation details. 2017. doi:10.1371/journal.pcbi.1005609.s001 apa: Lukacisinova, M., Novak, S., & Paixao, T. (2017). Modelling and simulation details. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609.s001 chicago: Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Modelling and Simulation Details.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.s001. ieee: M. Lukacisinova, S. Novak, and T. Paixao, “Modelling and simulation details.” Public Library of Science, 2017. ista: Lukacisinova M, Novak S, Paixao T. 2017. Modelling and simulation details, Public Library of Science, 10.1371/journal.pcbi.1005609.s001. mla: Lukacisinova, Marta, et al. Modelling and Simulation Details. Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.s001. short: M. Lukacisinova, S. Novak, T. Paixao, (2017). date_created: 2021-08-09T14:02:34Z date_published: 2017-07-18T00:00:00Z date_updated: 2023-02-23T12:55:39Z day: '18' department: - _id: ToBo - _id: NiBa - _id: CaGu doi: 10.1371/journal.pcbi.1005609.s001 month: '07' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '696' relation: used_in_publication status: public status: public title: Modelling and simulation details type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2017' ... --- _id: '9850' abstract: - lang: eng text: In this text, we discuss how a cost of resistance and the possibility of lethal mutations impact our model. article_processing_charge: No author: - first_name: Marta full_name: Lukacisinova, Marta id: 4342E402-F248-11E8-B48F-1D18A9856A87 last_name: Lukacisinova orcid: 0000-0002-2519-8004 - first_name: Sebastian full_name: Novak, Sebastian id: 461468AE-F248-11E8-B48F-1D18A9856A87 last_name: Novak - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 citation: ama: Lukacisinova M, Novak S, Paixao T. Extensions of the model. 2017. doi:10.1371/journal.pcbi.1005609.s002 apa: Lukacisinova, M., Novak, S., & Paixao, T. (2017). Extensions of the model. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609.s002 chicago: Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Extensions of the Model.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.s002. ieee: M. Lukacisinova, S. Novak, and T. Paixao, “Extensions of the model.” Public Library of Science, 2017. ista: Lukacisinova M, Novak S, Paixao T. 2017. Extensions of the model, Public Library of Science, 10.1371/journal.pcbi.1005609.s002. mla: Lukacisinova, Marta, et al. Extensions of the Model. Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.s002. short: M. Lukacisinova, S. Novak, T. Paixao, (2017). date_created: 2021-08-09T14:05:24Z date_published: 2017-07-18T00:00:00Z date_updated: 2023-02-23T12:55:39Z day: '18' department: - _id: ToBo - _id: CaGu - _id: NiBa doi: 10.1371/journal.pcbi.1005609.s002 month: '07' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '696' relation: used_in_publication status: public status: public title: Extensions of the model type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2017' ... --- _id: '9846' article_processing_charge: No author: - first_name: Nela full_name: Nikolic, Nela id: 42D9CABC-F248-11E8-B48F-1D18A9856A87 last_name: Nikolic orcid: 0000-0001-9068-6090 - first_name: Frank full_name: Schreiber, Frank last_name: Schreiber - first_name: Alma full_name: Dal Co, Alma last_name: Dal Co - first_name: Daniel full_name: Kiviet, Daniel last_name: Kiviet - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Sten full_name: Littmann, Sten last_name: Littmann - first_name: Marcel full_name: Kuypers, Marcel last_name: Kuypers - first_name: Martin full_name: Ackermann, Martin last_name: Ackermann citation: ama: Nikolic N, Schreiber F, Dal Co A, et al. Supplementary methods. 2017. doi:10.1371/journal.pgen.1007122.s016 apa: Nikolic, N., Schreiber, F., Dal Co, A., Kiviet, D., Bergmiller, T., Littmann, S., … Ackermann, M. (2017). Supplementary methods. Public Library of Science. https://doi.org/10.1371/journal.pgen.1007122.s016 chicago: Nikolic, Nela, Frank Schreiber, Alma Dal Co, Daniel Kiviet, Tobias Bergmiller, Sten Littmann, Marcel Kuypers, and Martin Ackermann. “Supplementary Methods.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pgen.1007122.s016. ieee: N. Nikolic et al., “Supplementary methods.” Public Library of Science, 2017. ista: Nikolic N, Schreiber F, Dal Co A, Kiviet D, Bergmiller T, Littmann S, Kuypers M, Ackermann M. 2017. Supplementary methods, Public Library of Science, 10.1371/journal.pgen.1007122.s016. mla: Nikolic, Nela, et al. Supplementary Methods. Public Library of Science, 2017, doi:10.1371/journal.pgen.1007122.s016. short: N. Nikolic, F. Schreiber, A. Dal Co, D. Kiviet, T. Bergmiller, S. Littmann, M. Kuypers, M. Ackermann, (2017). date_created: 2021-08-09T13:35:17Z date_published: 2017-12-18T00:00:00Z date_updated: 2023-02-23T12:25:04Z day: '18' department: - _id: CaGu doi: 10.1371/journal.pgen.1007122.s016 month: '12' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '541' relation: used_in_publication status: public status: public title: Supplementary methods type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2017' ... --- _id: '9851' abstract: - lang: eng text: Based on the intuitive derivation of the dynamics of SIM allele frequency pM in the main text, we present a heuristic prediction for the long-term SIM allele frequencies with χ > 1 stresses and compare it to numerical simulations. article_processing_charge: No author: - first_name: Marta full_name: Lukacisinova, Marta id: 4342E402-F248-11E8-B48F-1D18A9856A87 last_name: Lukacisinova orcid: 0000-0002-2519-8004 - first_name: Sebastian full_name: Novak, Sebastian id: 461468AE-F248-11E8-B48F-1D18A9856A87 last_name: Novak - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 citation: ama: Lukacisinova M, Novak S, Paixao T. Heuristic prediction for multiple stresses. 2017. doi:10.1371/journal.pcbi.1005609.s003 apa: Lukacisinova, M., Novak, S., & Paixao, T. (2017). Heuristic prediction for multiple stresses. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609.s003 chicago: Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Heuristic Prediction for Multiple Stresses.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.s003. ieee: M. Lukacisinova, S. Novak, and T. Paixao, “Heuristic prediction for multiple stresses.” Public Library of Science, 2017. ista: Lukacisinova M, Novak S, Paixao T. 2017. Heuristic prediction for multiple stresses, Public Library of Science, 10.1371/journal.pcbi.1005609.s003. mla: Lukacisinova, Marta, et al. Heuristic Prediction for Multiple Stresses. Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.s003. short: M. Lukacisinova, S. Novak, T. Paixao, (2017). date_created: 2021-08-09T14:08:14Z date_published: 2017-07-18T00:00:00Z date_updated: 2023-02-23T12:55:39Z day: '18' department: - _id: ToBo - _id: CaGu - _id: NiBa doi: 10.1371/journal.pcbi.1005609.s003 month: '07' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '696' relation: used_in_publication status: public status: public title: Heuristic prediction for multiple stresses type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2017' ... --- _id: '9852' abstract: - lang: eng text: We show how different combination strategies affect the fraction of individuals that are multi-resistant. article_processing_charge: No author: - first_name: Marta full_name: Lukacisinova, Marta id: 4342E402-F248-11E8-B48F-1D18A9856A87 last_name: Lukacisinova orcid: 0000-0002-2519-8004 - first_name: Sebastian full_name: Novak, Sebastian id: 461468AE-F248-11E8-B48F-1D18A9856A87 last_name: Novak - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 citation: ama: Lukacisinova M, Novak S, Paixao T. Resistance frequencies for different combination strategies. 2017. doi:10.1371/journal.pcbi.1005609.s004 apa: Lukacisinova, M., Novak, S., & Paixao, T. (2017). Resistance frequencies for different combination strategies. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609.s004 chicago: Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Resistance Frequencies for Different Combination Strategies.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.s004. ieee: M. Lukacisinova, S. Novak, and T. Paixao, “Resistance frequencies for different combination strategies.” Public Library of Science, 2017. ista: Lukacisinova M, Novak S, Paixao T. 2017. Resistance frequencies for different combination strategies, Public Library of Science, 10.1371/journal.pcbi.1005609.s004. mla: Lukacisinova, Marta, et al. Resistance Frequencies for Different Combination Strategies. Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.s004. short: M. Lukacisinova, S. Novak, T. Paixao, (2017). date_created: 2021-08-09T14:11:40Z date_published: 2017-07-18T00:00:00Z date_updated: 2023-02-23T12:55:39Z day: '18' department: - _id: ToBo - _id: CaGu - _id: NiBa doi: 10.1371/journal.pcbi.1005609.s004 month: '07' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '696' relation: used_in_publication status: public status: public title: Resistance frequencies for different combination strategies type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2017' ... --- _id: '9844' article_processing_charge: No author: - first_name: Nela full_name: Nikolic, Nela id: 42D9CABC-F248-11E8-B48F-1D18A9856A87 last_name: Nikolic orcid: 0000-0001-9068-6090 - first_name: Frank full_name: Schreiber, Frank last_name: Schreiber - first_name: Alma full_name: Dal Co, Alma last_name: Dal Co - first_name: Daniel full_name: Kiviet, Daniel last_name: Kiviet - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Sten full_name: Littmann, Sten last_name: Littmann - first_name: Marcel full_name: Kuypers, Marcel last_name: Kuypers - first_name: Martin full_name: Ackermann, Martin last_name: Ackermann citation: ama: Nikolic N, Schreiber F, Dal Co A, et al. Source data for figures and tables. 2017. doi:10.1371/journal.pgen.1007122.s018 apa: Nikolic, N., Schreiber, F., Dal Co, A., Kiviet, D., Bergmiller, T., Littmann, S., … Ackermann, M. (2017). Source data for figures and tables. Public Library of Science. https://doi.org/10.1371/journal.pgen.1007122.s018 chicago: Nikolic, Nela, Frank Schreiber, Alma Dal Co, Daniel Kiviet, Tobias Bergmiller, Sten Littmann, Marcel Kuypers, and Martin Ackermann. “Source Data for Figures and Tables.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pgen.1007122.s018. ieee: N. Nikolic et al., “Source data for figures and tables.” Public Library of Science, 2017. ista: Nikolic N, Schreiber F, Dal Co A, Kiviet D, Bergmiller T, Littmann S, Kuypers M, Ackermann M. 2017. Source data for figures and tables, Public Library of Science, 10.1371/journal.pgen.1007122.s018. mla: Nikolic, Nela, et al. Source Data for Figures and Tables. Public Library of Science, 2017, doi:10.1371/journal.pgen.1007122.s018. short: N. Nikolic, F. Schreiber, A. Dal Co, D. Kiviet, T. Bergmiller, S. Littmann, M. Kuypers, M. Ackermann, (2017). date_created: 2021-08-09T13:27:16Z date_published: 2017-12-18T00:00:00Z date_updated: 2023-02-23T12:25:04Z day: '18' department: - _id: CaGu doi: 10.1371/journal.pgen.1007122.s018 month: '12' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '541' relation: used_in_publication status: public status: public title: Source data for figures and tables type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2017' ... --- _id: '561' abstract: - lang: eng text: Restriction–modification systems are widespread genetic elements that protect bacteria from bacteriophage infections by recognizing and cleaving heterologous DNA at short, well-defined sequences called restriction sites. Bioinformatic evidence shows that restriction sites are significantly underrepresented in bacteriophage genomes, presumably because bacteriophages with fewer restriction sites are more likely to escape cleavage by restriction–modification systems. However, how mutations in restriction sites affect the likelihood of bacteriophage escape is unknown. Using the bacteriophage l and the restriction–modification system EcoRI, we show that while mutation effects at different restriction sites are unequal, they are independent. As a result, the probability of bacteriophage escape increases with each mutated restriction site. Our results experimentally support the role of restriction site avoidance as a response to selection imposed by restriction–modification systems and offer an insight into the events underlying the process of bacteriophage escape. acknowledgement: This work was funded by an HFSP Young Investigators' grant RGY0079/2011 (C.C.G.). M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute of Science and Technology Austria. article_number: '20170646' article_processing_charge: No article_type: original author: - 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 citation: ama: Pleska M, Guet CC. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 2017;13(12). doi:10.1098/rsbl.2017.0646 apa: Pleska, M., & Guet, C. C. (2017). Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. The Royal Society. https://doi.org/10.1098/rsbl.2017.0646 chicago: Pleska, Maros, and Calin C Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” Biology Letters. The Royal Society, 2017. https://doi.org/10.1098/rsbl.2017.0646. ieee: M. Pleska and C. C. Guet, “Effects of mutations in phage restriction sites during escape from restriction–modification,” Biology Letters, vol. 13, no. 12. The Royal Society, 2017. ista: Pleska M, Guet CC. 2017. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 13(12), 20170646. mla: Pleska, Maros, and Calin C. Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” Biology Letters, vol. 13, no. 12, 20170646, The Royal Society, 2017, doi:10.1098/rsbl.2017.0646. short: M. Pleska, C.C. Guet, Biology Letters 13 (2017). date_created: 2018-12-11T11:47:11Z date_published: 2017-12-01T00:00:00Z date_updated: 2023-09-07T11:59:32Z day: '01' department: - _id: CaGu doi: 10.1098/rsbl.2017.0646 external_id: pmid: - '29237814' intvolume: ' 13' issue: '12' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1098/rsbl.2017.0646 month: '12' oa: 1 oa_version: Published Version pmid: 1 project: - _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: Biology Letters publication_identifier: issn: - 1744-9561 publication_status: published publisher: The Royal Society publist_id: '7253' quality_controlled: '1' related_material: record: - id: '9847' relation: research_data status: public - id: '202' relation: dissertation_contains status: public scopus_import: '1' status: public title: Effects of mutations in phage restriction sites during escape from restriction–modification type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 13 year: '2017' ... --- _id: '202' abstract: - lang: eng text: 'Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions.' acknowledgement: "During my PhD studies, I received help from many people, all of which unfortunately cannot be listed here. I thank them deeply and hope that I never made them regret their kindness.\r\nI would like to express my deepest gratitude to Călin Guet, who went far beyond his responsibilities as an advisor and was to me also a great mentor and a friend. Călin never questioned my potential or lacked compassion and I cannot thank him enough for cultivating in me an independent scientist. I was amazed by his ability to recognize the most fascinating scientific problems in objects of study that others would find mundane. I hope I adopted at least a fraction of this ability.\r\nI will be forever grateful to Bruce Levin for all his support and especially for giving me the best possible example of how one can practice excellent science with humor and style. Working with Bruce was a true privilege.\r\nI thank Jonathan Bollback and Gašper Tkačik for serving in my PhD committee and the Austrian Academy of Science for funding my PhD research via the DOC fellowship.\r\nI thank all our lab members: Tobias Bergmiller for his guidance, especially in the first years of my research, and for being a good friend throughout; Remy Chait for staying in the lab at unreasonable hours and for the good laughs at bad jokes we shared; Anna Staron for supportively listening to my whines whenever I had to run a gel; Magdalena Steinrück for her pioneering work in the lab; Kathrin Tomasek for keeping the entropic forces in check and for her FACS virtuosity; Isabella Tomanek for always being nice to me, no matter how much bench space I took from her.\r\nI thank all my collaborators: Reiko Okura and Yuichi Wakamoto for performing and analyzing the microfluidic experiments; Long Qian and Edo Kussell for their bioinformatics analysis; Dominik Refardt for the λ kan phage; Moritz for his help with the mathematical modeling. I thank Fabienne Jesse for her tireless editorial work on all our manuscripts.\r\nFinally, I would like to thank my family and especially my wife Edita, who sacrificed a lot so that I can pursue my goals and dreams.\r\n" alternative_title: - ISTA Thesis 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 citation: ama: Pleska M. Biology of restriction-modification systems at the single-cell and population level. 2017. doi:10.15479/AT:ISTA:th_916 apa: Pleska, M. (2017). Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_916 chicago: Pleska, Maros. “Biology of Restriction-Modification Systems at the Single-Cell and Population Level.” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:th_916. ieee: M. Pleska, “Biology of restriction-modification systems at the single-cell and population level,” Institute of Science and Technology Austria, 2017. ista: Pleska M. 2017. Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria. mla: Pleska, Maros. Biology of Restriction-Modification Systems at the Single-Cell and Population Level. Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:th_916. short: M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell and Population Level, Institute of Science and Technology Austria, 2017. date_created: 2018-12-11T11:45:10Z date_published: 2017-10-01T00:00:00Z date_updated: 2023-09-15T12:04:56Z day: '01' ddc: - '576' - '579' degree_awarded: PhD department: - _id: CaGu doi: 10.15479/AT:ISTA:th_916 file: - access_level: open_access checksum: 33cfb59674e91f82e3738396d3fb3776 content_type: application/pdf creator: system date_created: 2018-12-12T10:08:48Z date_updated: 2020-07-14T12:45:24Z file_id: '4710' file_name: IST-2018-916-v1+3_2017_Pleska_Maros_Thesis.pdf file_size: 18569590 relation: main_file - access_level: closed checksum: dcc239968decb233e7f98cf1083d8c26 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dernst date_created: 2019-04-05T08:33:14Z date_updated: 2020-07-14T12:45:24Z file_id: '6204' file_name: 2017_Pleska_Maros_Thesis.docx file_size: 2801649 relation: source_file file_date_updated: 2020-07-14T12:45:24Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '126' 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 (DOC Fellowship) publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '7711' pubrep_id: '916' related_material: record: - id: '1243' relation: part_of_dissertation status: public - id: '561' relation: part_of_dissertation status: public - id: '457' 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: Biology of restriction-modification systems at the single-cell and population level tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2017' ... --- _id: '1351' abstract: - lang: eng text: The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs—an important problem of interest in evolutionary biology—more efficiently than the classical simulation method. We specify the property in linear temporal logic. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights. article_processing_charge: No author: - first_name: Mirco full_name: Giacobbe, Mirco id: 3444EA5E-F248-11E8-B48F-1D18A9856A87 last_name: Giacobbe orcid: 0000-0001-8180-0904 - 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: Ashutosh full_name: Gupta, Ashutosh id: 335E5684-F248-11E8-B48F-1D18A9856A87 last_name: Gupta - 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: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 citation: ama: Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. Model checking the evolution of gene regulatory networks. Acta Informatica. 2017;54(8):765-787. doi:10.1007/s00236-016-0278-x apa: Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., & Petrov, T. (2017). Model checking the evolution of gene regulatory networks. Acta Informatica. Springer. https://doi.org/10.1007/s00236-016-0278-x chicago: Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago Paixao, and Tatjana Petrov. “Model Checking the Evolution of Gene Regulatory Networks.” Acta Informatica. Springer, 2017. https://doi.org/10.1007/s00236-016-0278-x. ieee: M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov, “Model checking the evolution of gene regulatory networks,” Acta Informatica, vol. 54, no. 8. Springer, pp. 765–787, 2017. ista: Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. 2017. Model checking the evolution of gene regulatory networks. Acta Informatica. 54(8), 765–787. mla: Giacobbe, Mirco, et al. “Model Checking the Evolution of Gene Regulatory Networks.” Acta Informatica, vol. 54, no. 8, Springer, 2017, pp. 765–87, doi:10.1007/s00236-016-0278-x. short: M. Giacobbe, C.C. Guet, A. Gupta, T.A. Henzinger, T. Paixao, T. Petrov, Acta Informatica 54 (2017) 765–787. date_created: 2018-12-11T11:51:32Z date_published: 2017-12-01T00:00:00Z date_updated: 2023-09-20T11:06:03Z day: '01' ddc: - '006' - '576' department: - _id: ToHe - _id: CaGu - _id: NiBa doi: 10.1007/s00236-016-0278-x ec_funded: 1 external_id: isi: - '000414343200003' file: - access_level: open_access checksum: 4e661d9135d7f8c342e8e258dee76f3e content_type: application/pdf creator: dernst date_created: 2019-01-17T15:57:29Z date_updated: 2020-07-14T12:44:46Z file_id: '5841' file_name: 2017_ActaInformatica_Giacobbe.pdf file_size: 755241 relation: main_file file_date_updated: 2020-07-14T12:44:46Z has_accepted_license: '1' intvolume: ' 54' isi: 1 issue: '8' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 765 - 787 project: - _id: 25EE3708-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '267989' name: Quantitative Reactive Modeling - _id: 25832EC2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S 11407_N23 name: Rigorous Systems Engineering - _id: 25F42A32-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z211 name: The Wittgenstein Prize - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 25B07788-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '250152' name: Limits to selection in biology and in evolutionary computation publication: Acta Informatica publication_identifier: issn: - '00015903' publication_status: published publisher: Springer publist_id: '5898' pubrep_id: '649' quality_controlled: '1' related_material: record: - id: '1835' relation: earlier_version status: public scopus_import: '1' status: public title: Model checking the evolution of gene regulatory networks 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: 54 year: '2017' ... --- _id: '1336' abstract: - lang: eng text: Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse the runtimes of EAs on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrences of new mutations is much longer than the time it takes for a mutated genotype to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a stochastic process evolving one genotype by means of mutation and selection between the resident and the mutated genotype. The probability of accepting the mutated genotype then depends on the change in fitness. We study this process, SSWM, from an algorithmic perspective, quantifying its expected optimisation time for various parameters and investigating differences to a similar evolutionary algorithm, the well-known (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient. article_processing_charge: No author: - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Jorge full_name: Pérez Heredia, Jorge last_name: Pérez Heredia - first_name: Dirk full_name: Sudholt, Dirk last_name: Sudholt - first_name: Barbora full_name: Trubenova, Barbora id: 42302D54-F248-11E8-B48F-1D18A9856A87 last_name: Trubenova orcid: 0000-0002-6873-2967 citation: ama: Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. Towards a runtime comparison of natural and artificial evolution. Algorithmica. 2017;78(2):681-713. doi:10.1007/s00453-016-0212-1 apa: Paixao, T., Pérez Heredia, J., Sudholt, D., & Trubenova, B. (2017). Towards a runtime comparison of natural and artificial evolution. Algorithmica. Springer. https://doi.org/10.1007/s00453-016-0212-1 chicago: Paixao, Tiago, Jorge Pérez Heredia, Dirk Sudholt, and Barbora Trubenova. “Towards a Runtime Comparison of Natural and Artificial Evolution.” Algorithmica. Springer, 2017. https://doi.org/10.1007/s00453-016-0212-1. ieee: T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “Towards a runtime comparison of natural and artificial evolution,” Algorithmica, vol. 78, no. 2. Springer, pp. 681–713, 2017. ista: Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. 2017. Towards a runtime comparison of natural and artificial evolution. Algorithmica. 78(2), 681–713. mla: Paixao, Tiago, et al. “Towards a Runtime Comparison of Natural and Artificial Evolution.” Algorithmica, vol. 78, no. 2, Springer, 2017, pp. 681–713, doi:10.1007/s00453-016-0212-1. short: T. Paixao, J. Pérez Heredia, D. Sudholt, B. Trubenova, Algorithmica 78 (2017) 681–713. date_created: 2018-12-11T11:51:27Z date_published: 2017-06-01T00:00:00Z date_updated: 2023-09-20T11:14:42Z day: '01' ddc: - '576' department: - _id: NiBa - _id: CaGu doi: 10.1007/s00453-016-0212-1 ec_funded: 1 external_id: isi: - '000400379500013' file: - access_level: open_access checksum: 7873f665a0c598ac747c908f34cb14b9 content_type: application/pdf creator: system date_created: 2018-12-12T10:10:19Z date_updated: 2020-07-14T12:44:44Z file_id: '4805' file_name: IST-2016-658-v1+1_s00453-016-0212-1.pdf file_size: 710206 relation: main_file file_date_updated: 2020-07-14T12:44:44Z has_accepted_license: '1' intvolume: ' 78' isi: 1 issue: '2' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: 681 - 713 project: - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation publication: Algorithmica publication_identifier: issn: - '01784617' publication_status: published publisher: Springer publist_id: '5931' pubrep_id: '658' quality_controlled: '1' scopus_import: '1' status: public title: Towards a runtime comparison of natural and artificial evolution 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: 78 year: '2017' ... --- _id: '1084' abstract: - lang: eng text: 'BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities.' article_processing_charge: No author: - first_name: Chong full_name: Fang, Chong last_name: Fang - 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 - first_name: Martin full_name: Grafe, Martin last_name: Grafe - first_name: Ralf full_name: Heermann, Ralf last_name: Heermann - first_name: Kirsten full_name: Jung, Kirsten last_name: Jung - first_name: Susanne full_name: Gebhard, Susanne last_name: Gebhard - first_name: Thorsten full_name: Mascher, Thorsten last_name: Mascher citation: ama: Fang C, Nagy-Staron AA, Grafe M, et al. Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. 2017;104(1):16-31. doi:10.1111/mmi.13597 apa: Fang, C., Nagy-Staron, A. A., Grafe, M., Heermann, R., Jung, K., Gebhard, S., & Mascher, T. (2017). Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. Wiley-Blackwell. https://doi.org/10.1111/mmi.13597 chicago: Fang, Chong, Anna A Nagy-Staron, Martin Grafe, Ralf Heermann, Kirsten Jung, Susanne Gebhard, and Thorsten Mascher. “Insulation and Wiring Specificity of BceR like Response Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular Microbiology. Wiley-Blackwell, 2017. https://doi.org/10.1111/mmi.13597. ieee: C. Fang et al., “Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis,” Molecular Microbiology, vol. 104, no. 1. Wiley-Blackwell, pp. 16–31, 2017. ista: Fang C, Nagy-Staron AA, Grafe M, Heermann R, Jung K, Gebhard S, Mascher T. 2017. Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. 104(1), 16–31. mla: Fang, Chong, et al. “Insulation and Wiring Specificity of BceR like Response Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular Microbiology, vol. 104, no. 1, Wiley-Blackwell, 2017, pp. 16–31, doi:10.1111/mmi.13597. short: C. Fang, A.A. Nagy-Staron, M. Grafe, R. Heermann, K. Jung, S. Gebhard, T. Mascher, Molecular Microbiology 104 (2017) 16–31. date_created: 2018-12-11T11:50:03Z date_published: 2017-04-01T00:00:00Z date_updated: 2023-09-20T11:48:43Z day: '01' department: - _id: CaGu doi: 10.1111/mmi.13597 external_id: isi: - '000398059200002' intvolume: ' 104' isi: 1 issue: '1' language: - iso: eng month: '04' oa_version: None page: 16 - 31 publication: Molecular Microbiology publication_identifier: issn: - ' 0950382X' publication_status: published publisher: Wiley-Blackwell publist_id: '6294' quality_controlled: '1' scopus_import: '1' status: public title: Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 104 year: '2017' ... --- _id: '954' abstract: - lang: eng text: Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for. article_number: e25192 article_processing_charge: Yes author: - first_name: Mato full_name: Lagator, Mato id: 345D25EC-F248-11E8-B48F-1D18A9856A87 last_name: Lagator - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - 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: Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 2017;6. doi:10.7554/eLife.25192 apa: Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., & Guet, C. C. (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25192 chicago: Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25192. ieee: M. Lagator, T. Paixao, N. H. Barton, J. P. Bollback, and C. C. Guet, “On the mechanistic nature of epistasis in a canonical cis-regulatory element,” eLife, vol. 6. eLife Sciences Publications, 2017. ista: Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. 2017. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 6, e25192. mla: Lagator, Mato, et al. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife, vol. 6, e25192, eLife Sciences Publications, 2017, doi:10.7554/eLife.25192. short: M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017). date_created: 2018-12-11T11:49:23Z date_published: 2017-05-18T00:00:00Z date_updated: 2023-09-22T10:01:17Z day: '18' ddc: - '576' department: - _id: CaGu - _id: NiBa - _id: JoBo doi: 10.7554/eLife.25192 ec_funded: 1 external_id: isi: - '000404024800001' file: - access_level: open_access checksum: 59cdd4400fb41280122d414fea971546 content_type: application/pdf creator: system date_created: 2018-12-12T10:17:49Z date_updated: 2020-07-14T12:48:16Z file_id: '5306' file_name: IST-2017-841-v1+1_elife-25192-v2.pdf file_size: 2441529 relation: main_file - access_level: open_access checksum: b69024880558b858eb8c5d47a92b6377 content_type: application/pdf creator: system date_created: 2018-12-12T10:17:50Z date_updated: 2020-07-14T12:48:16Z file_id: '5307' file_name: IST-2017-841-v1+2_elife-25192-figures-v2.pdf file_size: 3752660 relation: main_file file_date_updated: 2020-07-14T12:48:16Z has_accepted_license: '1' intvolume: ' 6' isi: 1 language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation - _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 publication: eLife publication_identifier: issn: - 2050084X publication_status: published publisher: eLife Sciences Publications publist_id: '6460' pubrep_id: '841' quality_controlled: '1' scopus_import: '1' status: public title: On the mechanistic nature of epistasis in a canonical cis-regulatory element 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: 6 year: '2017' ... --- _id: '1007' abstract: - lang: eng text: 'A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input.' article_processing_charge: Yes (in subscription journal) author: - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Eduardo full_name: Sontag, Eduardo last_name: Sontag citation: ama: Lang M, Sontag E. Zeros of nonlinear systems with input invariances. Automatica. 2017;81C:46-55. doi:10.1016/j.automatica.2017.03.030 apa: Lang, M., & Sontag, E. (2017). Zeros of nonlinear systems with input invariances. Automatica. International Federation of Automatic Control. https://doi.org/10.1016/j.automatica.2017.03.030 chicago: Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica. International Federation of Automatic Control, 2017. https://doi.org/10.1016/j.automatica.2017.03.030. ieee: M. Lang and E. Sontag, “Zeros of nonlinear systems with input invariances,” Automatica, vol. 81C. International Federation of Automatic Control, pp. 46–55, 2017. ista: Lang M, Sontag E. 2017. Zeros of nonlinear systems with input invariances. Automatica. 81C, 46–55. mla: Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica, vol. 81C, International Federation of Automatic Control, 2017, pp. 46–55, doi:10.1016/j.automatica.2017.03.030. short: M. Lang, E. Sontag, Automatica 81C (2017) 46–55. date_created: 2018-12-11T11:49:39Z date_published: 2017-06-01T00:00:00Z date_updated: 2023-10-17T08:51:18Z day: '01' ddc: - '000' department: - _id: CaGu - _id: GaTk doi: 10.1016/j.automatica.2017.03.030 ec_funded: 1 external_id: isi: - '000403513900006' file: - access_level: open_access content_type: application/pdf creator: system date_created: 2018-12-12T10:11:29Z date_updated: 2018-12-12T10:11:29Z file_id: '4884' file_name: IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf file_size: 1401954 relation: main_file file_date_updated: 2018-12-12T10:11:29Z has_accepted_license: '1' isi: 1 language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: 46 - 55 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Automatica publication_identifier: issn: - 0005-1098 publication_status: published publisher: International Federation of Automatic Control publist_id: '6391' pubrep_id: '813' quality_controlled: '1' scopus_import: '1' status: public title: Zeros of nonlinear systems with input invariances 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: 81C year: '2017' ... --- _id: '5564' abstract: - lang: eng text: Compressed Fastq files with whole-genome sequencing data of IS-wt strain D and clones from four evolved populations (A11, C08, C10, D08). Information on this data collection is available in the Methods Section of the primary publication. 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 - 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: Steinrück M, Guet CC. Fastq files for “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.” 2017. doi:10.15479/AT:ISTA:65 apa: Steinrück, M., & Guet, C. C. (2017). Fastq files for “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:65 chicago: Steinrück, Magdalena, and Calin C Guet. “Fastq Files for ‘Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.’” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:65. ieee: M. Steinrück and C. C. Guet, “Fastq files for ‘Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.’” Institute of Science and Technology Austria, 2017. ista: Steinrück M, Guet CC. 2017. Fastq files for ‘Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:65. mla: Steinrück, Magdalena, and Calin C. Guet. Fastq Files for “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:65. short: M. Steinrück, C.C. Guet, (2017). datarep_id: '65' date_created: 2018-12-12T12:31:33Z date_published: 2017-04-11T00:00:00Z date_updated: 2024-02-21T13:47:28Z day: '11' ddc: - '576' department: - _id: CaGu doi: 10.15479/AT:ISTA:65 file: - access_level: open_access checksum: 31a0c01d022721073241a23d192cc37e content_type: application/zip creator: system date_created: 2018-12-12T13:03:18Z date_updated: 2020-07-14T12:47:03Z file_id: '5627' file_name: IST-2017-65-v1+1_D_anc_1.fastq.zip file_size: 1225959109 relation: main_file - access_level: open_access checksum: d8f26f83ce7e7e45436121f9c6cd9b83 content_type: application/zip creator: system date_created: 2018-12-12T13:03:30Z date_updated: 2020-07-14T12:47:03Z file_id: '5628' file_name: IST-2017-65-v1+1_D_anc_2.fastq.zip file_size: 1422656107 relation: main_file - access_level: open_access checksum: e07b99bcfe55b5f132ca03b8b48c8cbc content_type: application/zip creator: system date_created: 2018-12-12T13:03:33Z date_updated: 2020-07-14T12:47:03Z file_id: '5629' file_name: IST-2017-65-v1+2_D_A11_1.fastq.zip file_size: 565014975 relation: main_file - access_level: open_access checksum: eda86143d5f32d844b54f8530041e32b content_type: application/zip creator: system date_created: 2018-12-12T13:03:42Z date_updated: 2020-07-14T12:47:03Z file_id: '5630' file_name: IST-2017-65-v1+3_D_A11_2.fastq.zip file_size: 564490030 relation: main_file - access_level: open_access checksum: 906d44f950c1626d9b99f34fbf89cb12 content_type: application/zip creator: system date_created: 2018-12-12T13:03:46Z date_updated: 2020-07-14T12:47:03Z file_id: '5631' file_name: IST-2017-65-v1+4_D_C10_1.fastq.zip file_size: 875430169 relation: main_file - access_level: open_access checksum: 6ca14a032a79e0c787106bdf635725c9 content_type: application/zip creator: system date_created: 2018-12-12T13:03:54Z date_updated: 2020-07-14T12:47:03Z file_id: '5632' file_name: IST-2017-65-v1+6_D_C08_2.fastq.zip file_size: 638298201 relation: main_file - access_level: open_access checksum: 66ab16ddb5ba64b2e263ef746ebf2893 content_type: application/zip creator: system date_created: 2018-12-12T13:04:01Z date_updated: 2020-07-14T12:47:03Z file_id: '5633' file_name: IST-2017-65-v1+5_D_C10_2.fastq.zip file_size: 894702866 relation: main_file - access_level: open_access checksum: 82607970174f8d37773b7d3acc712195 content_type: application/zip creator: system date_created: 2018-12-12T13:04:07Z date_updated: 2020-07-14T12:47:03Z file_id: '5634' file_name: IST-2017-65-v1+7_D_C08_1.fastq.zip file_size: 623648989 relation: main_file - access_level: open_access checksum: 225c30b243268c7dda9d6f8327933252 content_type: application/zip creator: system date_created: 2018-12-12T13:04:11Z date_updated: 2020-07-14T12:47:03Z file_id: '5635' file_name: IST-2017-65-v1+8_D_D08_1.fastq.zip file_size: 259359583 relation: main_file file_date_updated: 2020-07-14T12:47:03Z has_accepted_license: '1' month: '04' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '704' relation: research_paper status: public status: public title: Fastq files for "Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection" 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: '2017' ... --- _id: '5560' abstract: - lang: eng text: "This repository contains the data collected for the manuscript \"Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity\".\r\nThe data is compressed into a single archive. Within the archive, different folders correspond to figures of the main text and the SI of the related publication.\r\nData is saved as plain text, with each folder containing a separate readme file describing the format. Typically, the data is from fluorescence microscopy measurements of single cells growing in a microfluidic \"mother machine\" device, and consists of relevant values (primarily arbitrary unit or normalized fluorescence measurements, and division times / growth rates) after raw microscopy images have been processed, segmented, and their features extracted, as described in the methods section of the related publication." 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: Anna M full_name: Andersson, Anna M id: 2B8A40DA-F248-11E8-B48F-1D18A9856A87 last_name: Andersson orcid: 0000-0003-2912-6769 - first_name: Kathrin full_name: Tomasek, Kathrin id: 3AEC8556-F248-11E8-B48F-1D18A9856A87 last_name: Tomasek orcid: 0000-0003-3768-877X - first_name: Enrique full_name: Balleza, Enrique last_name: Balleza - first_name: Daniel full_name: Kiviet, Daniel last_name: Kiviet - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Gasper full_name: Tkacik, Gasper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkacik 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: Bergmiller T, Andersson AM, Tomasek K, et al. Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity. 2017. doi:10.15479/AT:ISTA:53 apa: Bergmiller, T., Andersson, A. M., Tomasek, K., Balleza, E., Kiviet, D., Hauschild, R., … Guet, C. C. (2017). Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:53 chicago: Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza, Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning of the Multi-Drug Efflux Pump AcrAB-TolC Underlies Long-Lived Phenotypic Heterogeneity.” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:53. ieee: T. Bergmiller et al., “Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity.” Institute of Science and Technology Austria, 2017. ista: Bergmiller T, Andersson AM, Tomasek K, Balleza E, Kiviet D, Hauschild R, Tkačik G, Guet CC. 2017. Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity, Institute of Science and Technology Austria, 10.15479/AT:ISTA:53. mla: Bergmiller, Tobias, et al. Biased Partitioning of the Multi-Drug Efflux Pump AcrAB-TolC Underlies Long-Lived Phenotypic Heterogeneity. Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:53. short: T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild, G. Tkačik, C.C. Guet, (2017). datarep_id: '53' date_created: 2018-12-12T12:31:32Z date_published: 2017-03-10T00:00:00Z date_updated: 2024-02-21T13:49:00Z day: '10' ddc: - '571' department: - _id: CaGu - _id: GaTk - _id: Bio doi: 10.15479/AT:ISTA:53 file: - access_level: open_access checksum: d77859af757ac8025c50c7b12b52eaf3 content_type: application/zip creator: system date_created: 2018-12-12T13:02:38Z date_updated: 2020-07-14T12:47:03Z file_id: '5603' file_name: IST-2017-53-v1+1_Data_MDE.zip file_size: 6773204 relation: main_file file_date_updated: 2020-07-14T12:47:03Z has_accepted_license: '1' keyword: - single cell microscopy - mother machine microfluidic device - AcrAB-TolC pump - multi-drug efflux - Escherichia coli month: '03' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '665' relation: research_paper status: public status: public title: Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity 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: '2017' ... --- _id: '665' abstract: - lang: eng text: The molecular mechanisms underlying phenotypic variation in isogenic bacterial populations remain poorly understood.We report that AcrAB-TolC, the main multidrug efflux pump of Escherichia coli, exhibits a strong partitioning bias for old cell poles by a segregation mechanism that is mediated by ternary AcrAB-TolC complex formation. Mother cells inheriting old poles are phenotypically distinct and display increased drug efflux activity relative to daughters. Consequently, we find systematic and long-lived growth differences between mother and daughter cells in the presence of subinhibitory drug concentrations. A simple model for biased partitioning predicts a population structure of long-lived and highly heterogeneous phenotypes. This straightforward mechanism of generating sustained growth rate differences at subinhibitory antibiotic concentrations has implications for understanding the emergence of multidrug resistance in bacteria. article_processing_charge: No article_type: original author: - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Anna M full_name: Andersson, Anna M id: 2B8A40DA-F248-11E8-B48F-1D18A9856A87 last_name: Andersson orcid: 0000-0003-2912-6769 - first_name: Kathrin full_name: Tomasek, Kathrin id: 3AEC8556-F248-11E8-B48F-1D18A9856A87 last_name: Tomasek orcid: 0000-0003-3768-877X - first_name: Enrique full_name: Balleza, Enrique last_name: Balleza - first_name: Daniel full_name: Kiviet, Daniel last_name: Kiviet - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Gasper full_name: Tkacik, Gasper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkacik 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: Bergmiller T, Andersson AM, Tomasek K, et al. Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. 2017;356(6335):311-315. doi:10.1126/science.aaf4762 apa: Bergmiller, T., Andersson, A. M., Tomasek, K., Balleza, E., Kiviet, D., Hauschild, R., … Guet, C. C. (2017). Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aaf4762 chicago: Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza, Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” Science. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/science.aaf4762. ieee: T. Bergmiller et al., “Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity,” Science, vol. 356, no. 6335. American Association for the Advancement of Science, pp. 311–315, 2017. ista: Bergmiller T, Andersson AM, Tomasek K, Balleza E, Kiviet D, Hauschild R, Tkačik G, Guet CC. 2017. Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. 356(6335), 311–315. mla: Bergmiller, Tobias, et al. “Biased Partitioning of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” Science, vol. 356, no. 6335, American Association for the Advancement of Science, 2017, pp. 311–15, doi:10.1126/science.aaf4762. short: T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild, G. Tkačik, C.C. Guet, Science 356 (2017) 311–315. date_created: 2018-12-11T11:47:48Z date_published: 2017-04-21T00:00:00Z date_updated: 2024-02-21T13:49:00Z day: '21' department: - _id: CaGu - _id: GaTk - _id: Bio doi: 10.1126/science.aaf4762 intvolume: ' 356' issue: '6335' language: - iso: eng month: '04' oa_version: None page: 311 - 315 project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: Science publication_identifier: issn: - '00368075' publication_status: published publisher: American Association for the Advancement of Science publist_id: '7064' quality_controlled: '1' related_material: record: - id: '5560' relation: popular_science status: public scopus_import: 1 status: public title: Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 356 year: '2017' ... --- _id: '1028' abstract: - lang: eng text: Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination. In zebrafish embryos expressing fusion receptors, green light endowed control over aberrant fibroblast growth factor signaling during development. Green-light-induced domain dissociation and light-inactivated receptors will critically expand the optogenetic toolbox for control of biological processes. acknowledgement: "This work was supported by a grant from the European Union\U0010FC1Ds Seventh Framework Programme (CIG-303564). E.R. was supported by the graduate program MolecularDrugTargets (Austrian Science Fund (FWF), W1232) and a FemTech fellowship (Austrian Research Promotion Agency, 3580812)" article_processing_charge: No 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. Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. 2017;56(16):4608-4611. doi:10.1002/anie.201611998 apa: Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., & Janovjak, H. L. (2017). Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. Wiley-Blackwell. https://doi.org/10.1002/anie.201611998 chicago: Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel, and Harald L Janovjak. “Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition. Wiley-Blackwell, 2017. https://doi.org/10.1002/anie.201611998. ieee: S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak, “Green-light-induced inactivation of receptor signaling using cobalamin-binding domains,” Angewandte Chemie - International Edition, vol. 56, no. 16. Wiley-Blackwell, pp. 4608–4611, 2017. ista: Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017. Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. 56(16), 4608–4611. mla: Kainrath, Stephanie, et al. “Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition, vol. 56, no. 16, Wiley-Blackwell, 2017, pp. 4608–11, doi:10.1002/anie.201611998. short: S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak, Angewandte Chemie - International Edition 56 (2017) 4608–4611. date_created: 2018-12-11T11:49:46Z date_published: 2017-03-20T00:00:00Z date_updated: 2024-03-28T23:30:13Z day: '20' ddc: - '540' department: - _id: CaGu - _id: HaJa doi: 10.1002/anie.201611998 ec_funded: 1 external_id: isi: - '000398154000038' file: - access_level: open_access content_type: application/pdf creator: dernst date_created: 2019-01-18T09:39:55Z date_updated: 2019-01-18T09:39:55Z file_id: '5845' file_name: 2017_communications_Kainrath.pdf file_size: 2614942 relation: main_file success: 1 file_date_updated: 2019-01-18T09:39:55Z has_accepted_license: '1' intvolume: ' 56' isi: 1 issue: '16' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 4608-4611 project: - _id: 25548C20-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '303564' name: Microbial Ion Channels for Synthetic Neurobiology - _id: 26AA4EF2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets [do not use to be deleted] publication: Angewandte Chemie - International Edition publication_identifier: issn: - '14337851' publication_status: published publisher: Wiley-Blackwell publist_id: '6362' quality_controlled: '1' related_material: record: - id: '418' relation: dissertation_contains status: public - id: '7680' relation: part_of_dissertation status: public scopus_import: '1' status: public title: Green-light-induced inactivation of receptor signaling using cobalamin-binding domains 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: 56 year: '2017' ... --- _id: '704' abstract: - lang: eng text: 'How the organization of genes on a chromosome shapes adaptation is essential for understanding evolutionary paths. Here, we investigate how adaptation to rapidly increasing levels of antibiotic depends on the chromosomal neighborhood of a drug-resistance gene inserted at different positions of the Escherichia coli chromosome. Using a dual-fluorescence reporter that allows us to distinguish gene amplifications from other up-mutations, we track in real-time adaptive changes in expression of the drug-resistance gene. We find that the relative contribution of several mutation types differs systematically between loci due to properties of neighboring genes: essentiality, expression, orientation, termination, and presence of duplicates. These properties determine rate and fitness effects of gene amplification, deletions, and mutations compromising transcriptional termination. Thus, the adaptive potential of a gene under selection is a system-property with a complex genetic basis that is specific for each chromosomal locus, and it can be inferred from detailed functional and genomic data.' article_number: e25100 author: - first_name: Magdalena full_name: Steinrück, Magdalena id: 2C023F40-F248-11E8-B48F-1D18A9856A87 last_name: Steinrück orcid: 0000-0003-1229-9719 - 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: Steinrück M, Guet CC. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. eLife. 2017;6. doi:10.7554/eLife.25100 apa: Steinrück, M., & Guet, C. C. (2017). Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25100 chicago: Steinrück, Magdalena, and Calin C Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25100. ieee: M. Steinrück and C. C. Guet, “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection,” eLife, vol. 6. eLife Sciences Publications, 2017. ista: Steinrück M, Guet CC. 2017. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. eLife. 6, e25100. mla: Steinrück, Magdalena, and Calin C. Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” ELife, vol. 6, e25100, eLife Sciences Publications, 2017, doi:10.7554/eLife.25100. short: M. Steinrück, C.C. Guet, ELife 6 (2017). date_created: 2018-12-11T11:48:01Z date_published: 2017-07-25T00:00:00Z date_updated: 2024-03-28T23:30:28Z day: '25' ddc: - '576' department: - _id: CaGu doi: 10.7554/eLife.25100 file: - access_level: open_access checksum: 6b908b5db9f61f6820ebd7f8fa815571 content_type: application/pdf creator: system date_created: 2018-12-12T10:12:54Z date_updated: 2020-07-14T12:47:48Z file_id: '4975' file_name: IST-2017-890-v1+1_elife-25100-v1.pdf file_size: 2092088 relation: main_file - access_level: open_access checksum: ca21530389b720243552678125fdba35 content_type: application/pdf creator: system date_created: 2018-12-12T10:12:55Z date_updated: 2020-07-14T12:47:48Z file_id: '4976' file_name: IST-2017-890-v1+2_elife-25100-figures-v1.pdf file_size: 3428681 relation: main_file file_date_updated: 2020-07-14T12:47:48Z has_accepted_license: '1' intvolume: ' 6' language: - iso: eng month: '07' oa: 1 oa_version: Published Version publication: eLife publication_identifier: issn: - 2050084X publication_status: published publisher: eLife Sciences Publications publist_id: '6990' pubrep_id: '890' quality_controlled: '1' related_material: record: - id: '5564' relation: popular_science status: public - id: '26' relation: dissertation_contains status: public scopus_import: 1 status: public title: Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection 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: 6 year: '2017' ... --- _id: '696' abstract: - lang: eng text: Mutator strains are expected to evolve when the availability and effect of beneficial mutations are high enough to counteract the disadvantage from deleterious mutations that will inevitably accumulate. As the population becomes more adapted to its environment, both availability and effect of beneficial mutations necessarily decrease and mutation rates are predicted to decrease. It has been shown that certain molecular mechanisms can lead to increased mutation rates when the organism finds itself in a stressful environment. While this may be a correlated response to other functions, it could also be an adaptive mechanism, raising mutation rates only when it is most advantageous. Here, we use a mathematical model to investigate the plausibility of the adaptive hypothesis. We show that such a mechanism can be mantained if the population is subjected to diverse stresses. By simulating various antibiotic treatment schemes, we find that combination treatments can reduce the effectiveness of second-order selection on stress-induced mutagenesis. We discuss the implications of our results to strategies of antibiotic therapy. article_number: e1005609 article_type: original author: - first_name: Marta full_name: Lukacisinova, Marta id: 4342E402-F248-11E8-B48F-1D18A9856A87 last_name: Lukacisinova orcid: 0000-0002-2519-8004 - first_name: Sebastian full_name: Novak, Sebastian id: 461468AE-F248-11E8-B48F-1D18A9856A87 last_name: Novak orcid: 0000-0002-2519-824X - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 citation: ama: 'Lukacisinova M, Novak S, Paixao T. Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. 2017;13(7). doi:10.1371/journal.pcbi.1005609' apa: 'Lukacisinova, M., Novak, S., & Paixao, T. (2017). Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609' chicago: 'Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Stress Induced Mutagenesis: Stress Diversity Facilitates the Persistence of Mutator Genes.” PLoS Computational Biology. Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.' ieee: 'M. Lukacisinova, S. Novak, and T. Paixao, “Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes,” PLoS Computational Biology, vol. 13, no. 7. Public Library of Science, 2017.' ista: 'Lukacisinova M, Novak S, Paixao T. 2017. Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. 13(7), e1005609.' mla: 'Lukacisinova, Marta, et al. “Stress Induced Mutagenesis: Stress Diversity Facilitates the Persistence of Mutator Genes.” PLoS Computational Biology, vol. 13, no. 7, e1005609, Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.' short: M. Lukacisinova, S. Novak, T. Paixao, PLoS Computational Biology 13 (2017). date_created: 2018-12-11T11:47:58Z date_published: 2017-07-18T00:00:00Z date_updated: 2024-03-28T23:30:28Z day: '18' ddc: - '576' department: - _id: ToBo - _id: NiBa - _id: CaGu doi: 10.1371/journal.pcbi.1005609 ec_funded: 1 file: - access_level: open_access checksum: 9143c290fa6458ed2563bff4b295554a content_type: application/pdf creator: system date_created: 2018-12-12T10:15:01Z date_updated: 2020-07-14T12:47:46Z file_id: '5117' file_name: IST-2017-894-v1+1_journal.pcbi.1005609.pdf file_size: 3775716 relation: main_file file_date_updated: 2020-07-14T12:47:46Z has_accepted_license: '1' intvolume: ' 13' issue: '7' language: - iso: eng month: '07' oa: 1 oa_version: Published Version project: - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation publication: PLoS Computational Biology publication_identifier: issn: - 1553734X publication_status: published publisher: Public Library of Science publist_id: '7004' pubrep_id: '894' quality_controlled: '1' related_material: record: - id: '9849' relation: research_data status: public - id: '9850' relation: research_data status: public - id: '9851' relation: research_data status: public - id: '9852' relation: research_data status: public - id: '6263' relation: dissertation_contains status: public scopus_import: 1 status: public title: 'Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes' 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: 13 year: '2017' ... --- _id: '735' abstract: - lang: eng text: Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects development. Here, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling, and mesendoderm cell-fate specification during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo. article_processing_charge: No author: - first_name: Vanessa full_name: Barone, Vanessa id: 419EECCC-F248-11E8-B48F-1D18A9856A87 last_name: Barone orcid: 0000-0003-2676-3367 - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Gabriel full_name: Krens, Gabriel id: 2B819732-F248-11E8-B48F-1D18A9856A87 last_name: Krens orcid: 0000-0003-4761-5996 - first_name: Saurabh full_name: Pradhan, Saurabh last_name: Pradhan - first_name: Shayan full_name: Shamipour, Shayan id: 40B34FE2-F248-11E8-B48F-1D18A9856A87 last_name: Shamipour - first_name: Keisuke full_name: Sako, Keisuke id: 3BED66BE-F248-11E8-B48F-1D18A9856A87 last_name: Sako orcid: 0000-0002-6453-8075 - first_name: Mateusz K full_name: Sikora, Mateusz K id: 2F74BCDE-F248-11E8-B48F-1D18A9856A87 last_name: Sikora - 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: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 citation: ama: Barone V, Lang M, Krens G, et al. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 2017;43(2):198-211. doi:10.1016/j.devcel.2017.09.014 apa: Barone, V., Lang, M., Krens, G., Pradhan, S., Shamipour, S., Sako, K., … Heisenberg, C.-P. J. (2017). An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. Cell Press. https://doi.org/10.1016/j.devcel.2017.09.014 chicago: Barone, Vanessa, Moritz Lang, Gabriel Krens, Saurabh Pradhan, Shayan Shamipour, Keisuke Sako, Mateusz K Sikora, Calin C Guet, and Carl-Philipp J Heisenberg. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell. Cell Press, 2017. https://doi.org/10.1016/j.devcel.2017.09.014. ieee: V. Barone et al., “An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate,” Developmental Cell, vol. 43, no. 2. Cell Press, pp. 198–211, 2017. ista: Barone V, Lang M, Krens G, Pradhan S, Shamipour S, Sako K, Sikora MK, Guet CC, Heisenberg C-PJ. 2017. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 43(2), 198–211. mla: Barone, Vanessa, et al. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell, vol. 43, no. 2, Cell Press, 2017, pp. 198–211, doi:10.1016/j.devcel.2017.09.014. short: V. Barone, M. Lang, G. Krens, S. Pradhan, S. Shamipour, K. Sako, M.K. Sikora, C.C. Guet, C.-P.J. Heisenberg, Developmental Cell 43 (2017) 198–211. date_created: 2018-12-11T11:48:13Z date_published: 2017-10-23T00:00:00Z date_updated: 2024-03-28T23:30:39Z day: '23' department: - _id: CaHe - _id: CaGu - _id: GaTk doi: 10.1016/j.devcel.2017.09.014 ec_funded: 1 external_id: isi: - '000413443700011' intvolume: ' 43' isi: 1 issue: '2' language: - iso: eng month: '10' oa_version: None page: 198 - 211 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 252DD2A6-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I2058 name: 'Cell segregation in gastrulation: the role of cell fate specification' publication: Developmental Cell publication_identifier: issn: - '15345807' publication_status: published publisher: Cell Press publist_id: '6934' quality_controlled: '1' related_material: record: - id: '961' relation: dissertation_contains status: public - id: '8350' relation: dissertation_contains status: public scopus_import: '1' status: public title: An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 43 year: '2017' ... --- _id: '1008' abstract: - lang: eng text: Feedback loops in biological networks, among others, enable differentiation and cell cycle progression, and increase robustness in signal transduction. In natural networks, feedback loops are often complex and intertwined, making it challenging to identify which loops are mainly responsible for an observed behavior. However, minimal synthetic replicas could allow for such identification. Here, we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae to analyze if a transport-mediated positive feedback loop could be a core mechanism for the switch-like behavior in the regulation of metabolic gene networks such as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized the synthetic circuit using deterministic and stochastic mathematical models. Similar to its natural counterparts, our synthetic system shows bistable and hysteretic behavior, and the inducer concentration range for bistability as well as the switching rates between the two stable states depend on the repressor concentration. Our results indicate that a generic permease–inducer–repressor circuit with a single feedback loop is sufficient to explain the experimentally observed bistable behavior of the natural systems. We anticipate that the approach of reimplementing natural systems with orthogonal parts to identify crucial network components is applicable to other natural systems such as signaling pathways. acknowledgement: We thank Julio Polaina (Instituto de Agroqu ı ́ mica y Tecnolog ı ́ a de Alimentos, C.S.I.C., Paterna, Spain) for the gift of plasmid pMR4, Gregor W. Schmidt for provision of and support with the micro fl uidic device, Markus Du ̈ rr for the cell tracking R script, and Lukas Widmer for the script for MEIGO using “ parfor ” in MATLAB. We acknowledge the members of the Stelling group for discussions, comments, and support. author: - first_name: Robert full_name: Gnügge, Robert last_name: Gnügge - first_name: Lekshmi full_name: Dharmarajan, Lekshmi last_name: Dharmarajan - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Jörg full_name: Stelling, Jörg last_name: Stelling citation: ama: Gnügge R, Dharmarajan L, Lang M, Stelling J. An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. 2016;5(10):1098-1107. doi:10.1021/acssynbio.6b00013 apa: Gnügge, R., Dharmarajan, L., Lang, M., & Stelling, J. (2016). An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. American Chemical Society. https://doi.org/10.1021/acssynbio.6b00013 chicago: Gnügge, Robert, Lekshmi Dharmarajan, Moritz Lang, and Jörg Stelling. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS Synthetic Biology. American Chemical Society, 2016. https://doi.org/10.1021/acssynbio.6b00013. ieee: R. Gnügge, L. Dharmarajan, M. Lang, and J. Stelling, “An orthogonal permease–inducer–repressor feedback loop shows bistability,” ACS Synthetic Biology, vol. 5, no. 10. American Chemical Society, pp. 1098–1107, 2016. ista: Gnügge R, Dharmarajan L, Lang M, Stelling J. 2016. An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. 5(10), 1098–1107. mla: Gnügge, Robert, et al. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS Synthetic Biology, vol. 5, no. 10, American Chemical Society, 2016, pp. 1098–107, doi:10.1021/acssynbio.6b00013. short: R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling, ACS Synthetic Biology 5 (2016) 1098–1107. date_created: 2018-12-11T11:49:40Z date_published: 2016-05-05T00:00:00Z date_updated: 2021-01-12T06:47:37Z day: '05' department: - _id: CaGu doi: 10.1021/acssynbio.6b00013 intvolume: ' 5' issue: '10' language: - iso: eng month: '05' oa_version: None page: 1098 - 1107 publication: ACS Synthetic Biology publication_status: published publisher: American Chemical Society publist_id: '6390' quality_controlled: '1' status: public title: An orthogonal permease–inducer–repressor feedback loop shows bistability type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 5 year: '2016' ... --- _id: '1170' abstract: - lang: eng text: The increasing complexity of dynamic models in systems and synthetic biology poses computational challenges especially for the identification of model parameters. While modularization of the corresponding optimization problems could help reduce the “curse of dimensionality,” abundant feedback and crosstalk mechanisms prohibit a simple decomposition of most biomolecular networks into subnetworks, or modules. Drawing on ideas from network modularization and multiple-shooting optimization, we present here a modular parameter identification approach that explicitly allows for such interdependencies. Interfaces between our modules are given by the experimentally measured molecular species. This definition allows deriving good (initial) estimates for the inter-module communication directly from the experimental data. Given these estimates, the states and parameter sensitivities of different modules can be integrated independently. To achieve consistency between modules, we iteratively adjust the estimates for inter-module communication while optimizing the parameters. After convergence to an optimal parameter set---but not during earlier iterations---the intermodule communication as well as the individual modules\' state dynamics agree with the dynamics of the nonmodularized network. Our modular parameter identification approach allows for easy parallelization; it can reduce the computational complexity for larger networks and decrease the probability to converge to suboptimal local minima. We demonstrate the algorithm\'s performance in parameter estimation for two biomolecular networks, a synthetic genetic oscillator and a mammalian signaling pathway. author: - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Jörg full_name: Stelling, Jörg last_name: Stelling citation: ama: Lang M, Stelling J. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 2016;38(6):B988-B1008. doi:10.1137/15M103306X apa: Lang, M., & Stelling, J. (2016). Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics . https://doi.org/10.1137/15M103306X chicago: Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics , 2016. https://doi.org/10.1137/15M103306X. ieee: M. Lang and J. Stelling, “Modular parameter identification of biomolecular networks,” SIAM Journal on Scientific Computing, vol. 38, no. 6. Society for Industrial and Applied Mathematics , pp. B988–B1008, 2016. ista: Lang M, Stelling J. 2016. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 38(6), B988–B1008. mla: Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing, vol. 38, no. 6, Society for Industrial and Applied Mathematics , 2016, pp. B988–1008, doi:10.1137/15M103306X. short: M. Lang, J. Stelling, SIAM Journal on Scientific Computing 38 (2016) B988–B1008. date_created: 2018-12-11T11:50:31Z date_published: 2016-11-15T00:00:00Z date_updated: 2021-01-12T06:48:49Z day: '15' ddc: - '003' - '518' - '570' - '621' department: - _id: CaGu - _id: GaTk doi: 10.1137/15M103306X file: - access_level: local checksum: 781bc3ffd30b2dd65b7727c5a285fc78 content_type: application/pdf creator: system date_created: 2018-12-12T10:14:41Z date_updated: 2020-07-14T12:44:37Z file_id: '5095' file_name: IST-2017-811-v1+1_modular_parameter_identification.pdf file_size: 871964 relation: main_file file_date_updated: 2020-07-14T12:44:37Z has_accepted_license: '1' intvolume: ' 38' issue: '6' language: - iso: eng month: '11' oa_version: Submitted Version page: B988 - B1008 publication: SIAM Journal on Scientific Computing publication_status: published publisher: 'Society for Industrial and Applied Mathematics ' publist_id: '6186' pubrep_id: '811' quality_controlled: '1' scopus_import: 1 status: public title: Modular parameter identification of biomolecular networks type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 38 year: '2016' ... --- _id: '1220' abstract: - lang: eng text: Theoretical and numerical aspects of aerodynamic efficiency of propulsion systems coupled to the boundary layer of a fuselage are studied. We discuss the effects of local flow fields, which are affected both by conservative flow acceleration as well as total pressure losses, on the efficiency of boundary layer immersed propulsion devices. We introduce the concept of a boundary layer retardation turbine that helps reduce skin friction over the fuselage. We numerically investigate efficiency gains offered by boundary layer and wake interacting devices. We discuss the results in terms of a total energy consumption framework and show that efficiency gains of any device depend on all the other elements of the propulsion system. author: - first_name: Gregor full_name: Mikić, Gregor last_name: Mikić - first_name: Alex full_name: Stoll, Alex last_name: Stoll - first_name: Joe full_name: Bevirt, Joe last_name: Bevirt - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Mark full_name: Moore, Mark last_name: Moore citation: ama: 'Mikić G, Stoll A, Bevirt J, Grah R, Moore M. Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency. In: AIAA; 2016:1-19. doi:10.2514/6.2016-3764' apa: 'Mikić, G., Stoll, A., Bevirt, J., Grah, R., & Moore, M. (2016). Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency (pp. 1–19). Presented at the AIAA: Aviation Technology, Integration, and Operations Conference, Washington, D.C., USA: AIAA. https://doi.org/10.2514/6.2016-3764' chicago: Mikić, Gregor, Alex Stoll, Joe Bevirt, Rok Grah, and Mark Moore. “Fuselage Boundary Layer Ingestion Propulsion Applied to a Thin Haul Commuter Aircraft for Optimal Efficiency,” 1–19. AIAA, 2016. https://doi.org/10.2514/6.2016-3764. ieee: 'G. Mikić, A. Stoll, J. Bevirt, R. Grah, and M. Moore, “Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency,” presented at the AIAA: Aviation Technology, Integration, and Operations Conference, Washington, D.C., USA, 2016, pp. 1–19.' ista: 'Mikić G, Stoll A, Bevirt J, Grah R, Moore M. 2016. Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency. AIAA: Aviation Technology, Integration, and Operations Conference, 1–19.' mla: Mikić, Gregor, et al. Fuselage Boundary Layer Ingestion Propulsion Applied to a Thin Haul Commuter Aircraft for Optimal Efficiency. AIAA, 2016, pp. 1–19, doi:10.2514/6.2016-3764. short: G. Mikić, A. Stoll, J. Bevirt, R. Grah, M. Moore, in:, AIAA, 2016, pp. 1–19. conference: end_date: 2016-06-17 location: Washington, D.C., USA name: 'AIAA: Aviation Technology, Integration, and Operations Conference' start_date: 2016-06-13 date_created: 2018-12-11T11:50:47Z date_published: 2016-06-01T00:00:00Z date_updated: 2023-02-21T10:17:50Z day: '01' department: - _id: CaGu - _id: GaTk doi: 10.2514/6.2016-3764 language: - iso: eng main_file_link: - open_access: '1' url: https://ntrs.nasa.gov/search.jsp?R=20160010167&hterms=Fuselage+boundary+layer+ingestion+propulsion+applied+thin+haul+commuter+aircraft+optimal+efficiency&qs=N%3D0%26Ntk%3DAll%26Ntt%3DFuselage%2520boundary%2520layer%2520ingestion%2520propulsion%2520applied%2520to%2520a%2520thin%2520haul%2520commuter%2520aircraft%2520for%2520optimal%2520efficiency%26Ntx%3Dmode%2520matchallpartial%26Nm%3D123%7CCollection%7CNASA%2520STI%7C%7C17%7CCollection%7CNACA month: '06' oa: 1 oa_version: Preprint page: 1 - 19 publication_status: published publisher: AIAA publist_id: '6114' quality_controlled: '1' scopus_import: 1 status: public title: Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency type: conference user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 year: '2016' ... --- _id: '1290' abstract: - lang: eng text: We developed a competition-based screening strategy to identify compounds that invert the selective advantage of antibiotic resistance. Using our assay, we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram. Treating a tetracycline-resistant population with β-thujaplicin selects for loss of the resistance gene, enabling an effective second-phase treatment with doxycycline. acknowledgement: "This work was supported in part by National Institute of Allergy and Infectious Diseases grant U54 AI057159, US National Institutes of Health grants R01 GM081617 (to R.K.) and GM086258 (to J.C.), European Research Council FP7 ERC grant 281891 (to R.K.) and a National Science Foundation Graduate Fellowship (to L.K.S.).\r\n" author: - first_name: Laura full_name: Stone, Laura last_name: Stone - first_name: Michael full_name: Baym, Michael last_name: Baym - first_name: Tami full_name: Lieberman, Tami last_name: Lieberman - 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: Jon full_name: Clardy, Jon last_name: Clardy - first_name: Roy full_name: Kishony, Roy last_name: Kishony citation: ama: Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. 2016;12(11):902-904. doi:10.1038/nchembio.2176 apa: Stone, L., Baym, M., Lieberman, T., Chait, R. P., Clardy, J., & Kishony, R. (2016). Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. Nature Publishing Group. https://doi.org/10.1038/nchembio.2176 chicago: Stone, Laura, Michael Baym, Tami Lieberman, Remy P Chait, Jon Clardy, and Roy Kishony. “Compounds That Select against the Tetracycline-Resistance Efflux Pump.” Nature Chemical Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/nchembio.2176. ieee: L. Stone, M. Baym, T. Lieberman, R. P. Chait, J. Clardy, and R. Kishony, “Compounds that select against the tetracycline-resistance efflux pump,” Nature Chemical Biology, vol. 12, no. 11. Nature Publishing Group, pp. 902–904, 2016. ista: Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. 2016. Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. 12(11), 902–904. mla: Stone, Laura, et al. “Compounds That Select against the Tetracycline-Resistance Efflux Pump.” Nature Chemical Biology, vol. 12, no. 11, Nature Publishing Group, 2016, pp. 902–04, doi:10.1038/nchembio.2176. short: L. Stone, M. Baym, T. Lieberman, R.P. Chait, J. Clardy, R. Kishony, Nature Chemical Biology 12 (2016) 902–904. date_created: 2018-12-11T11:51:10Z date_published: 2016-11-01T00:00:00Z date_updated: 2021-01-12T06:49:39Z day: '01' department: - _id: CaGu - _id: GaTk doi: 10.1038/nchembio.2176 intvolume: ' 12' issue: '11' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069154/ month: '11' oa: 1 oa_version: Preprint page: 902 - 904 publication: Nature Chemical Biology publication_status: published publisher: Nature Publishing Group publist_id: '6026' quality_controlled: '1' scopus_import: 1 status: public title: Compounds that select against the tetracycline-resistance efflux pump type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 12 year: '2016' ... --- _id: '1320' abstract: - lang: eng text: 'In recent years, several biomolecular systems have been shown to be scale-invariant (SI), i.e. to show the same output dynamics when exposed to geometrically scaled input signals (u → pu, p > 0) after pre-adaptation to accordingly scaled constant inputs. In this article, we show that SI systems-as well as systems invariant with respect to other input transformations-can realize nonlinear differential operators: when excited by inputs obeying functional forms characteristic for a given class of invariant systems, the systems'' outputs converge to constant values directly quantifying the speed of the input.' acknowledgement: The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n° [291734]. Work supported in part by grants AFOSR FA9550-14-1-0060 and NIH 1R01GM100473. article_number: '7526722' author: - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Eduardo full_name: Sontag, Eduardo last_name: Sontag citation: ama: 'Lang M, Sontag E. Scale-invariant systems realize nonlinear differential operators. In: Vol 2016-July. IEEE; 2016. doi:10.1109/ACC.2016.7526722' apa: 'Lang, M., & Sontag, E. (2016). Scale-invariant systems realize nonlinear differential operators (Vol. 2016–July). Presented at the ACC: American Control Conference, Boston, MA, USA: IEEE. https://doi.org/10.1109/ACC.2016.7526722' chicago: Lang, Moritz, and Eduardo Sontag. “Scale-Invariant Systems Realize Nonlinear Differential Operators,” Vol. 2016–July. IEEE, 2016. https://doi.org/10.1109/ACC.2016.7526722. ieee: 'M. Lang and E. Sontag, “Scale-invariant systems realize nonlinear differential operators,” presented at the ACC: American Control Conference, Boston, MA, USA, 2016, vol. 2016–July.' ista: 'Lang M, Sontag E. 2016. Scale-invariant systems realize nonlinear differential operators. ACC: American Control Conference vol. 2016–July, 7526722.' mla: Lang, Moritz, and Eduardo Sontag. Scale-Invariant Systems Realize Nonlinear Differential Operators. Vol. 2016–July, 7526722, IEEE, 2016, doi:10.1109/ACC.2016.7526722. short: M. Lang, E. Sontag, in:, IEEE, 2016. conference: end_date: 2016-07-08 location: Boston, MA, USA name: 'ACC: American Control Conference' start_date: 2016-07-06 date_created: 2018-12-11T11:51:21Z date_published: 2016-07-28T00:00:00Z date_updated: 2021-01-12T06:49:51Z day: '28' ddc: - '003' - '621' department: - _id: CaGu - _id: GaTk doi: 10.1109/ACC.2016.7526722 ec_funded: 1 file: - access_level: local checksum: 7219432b43defc62a0d45f48d4ce6a19 content_type: application/pdf creator: system date_created: 2018-12-12T10:16:17Z date_updated: 2020-07-14T12:44:43Z file_id: '5203' file_name: IST-2017-810-v1+1_root.pdf file_size: 539166 relation: main_file file_date_updated: 2020-07-14T12:44:43Z has_accepted_license: '1' language: - iso: eng month: '07' oa_version: Preprint project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication_status: published publisher: IEEE publist_id: '5950' pubrep_id: '810' quality_controlled: '1' scopus_import: 1 status: public title: Scale-invariant systems realize nonlinear differential operators type: conference user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 2016-July year: '2016' ... --- _id: '1332' abstract: - lang: eng text: Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance. acknowledgement: This work was partially supported by US National Institutes of Health grant R01-GM081617, Israeli Centers of Research Excellence I-CORE Program ISF Grant No. 152/11, and the European Research Council FP7 ERC Grant 281891. article_number: '10333' author: - 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: Adam full_name: Palmer, Adam last_name: Palmer - first_name: Idan full_name: Yelin, Idan last_name: Yelin - first_name: Roy full_name: Kishony, Roy last_name: Kishony citation: ama: Chait RP, Palmer A, Yelin I, Kishony R. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. 2016;7. doi:10.1038/ncomms10333 apa: Chait, R. P., Palmer, A., Yelin, I., & Kishony, R. (2016). Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms10333 chicago: Chait, Remy P, Adam Palmer, Idan Yelin, and Roy Kishony. “Pervasive Selection for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.” Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms10333. ieee: R. P. Chait, A. Palmer, I. Yelin, and R. Kishony, “Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments,” Nature Communications, vol. 7. Nature Publishing Group, 2016. ista: Chait RP, Palmer A, Yelin I, Kishony R. 2016. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. 7, 10333. mla: Chait, Remy P., et al. “Pervasive Selection for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.” Nature Communications, vol. 7, 10333, Nature Publishing Group, 2016, doi:10.1038/ncomms10333. short: R.P. Chait, A. Palmer, I. Yelin, R. Kishony, Nature Communications 7 (2016). date_created: 2018-12-11T11:51:25Z date_published: 2016-01-20T00:00:00Z date_updated: 2021-01-12T06:49:57Z day: '20' ddc: - '570' - '579' department: - _id: CaGu - _id: GaTk doi: 10.1038/ncomms10333 file: - access_level: open_access checksum: ef147bcbb8bd37e9079cf3ce06f5815d content_type: application/pdf creator: system date_created: 2018-12-12T10:13:52Z date_updated: 2020-07-14T12:44:44Z file_id: '5039' file_name: IST-2016-662-v1+1_ncomms10333.pdf file_size: 1844107 relation: main_file file_date_updated: 2020-07-14T12:44:44Z has_accepted_license: '1' intvolume: ' 7' language: - iso: eng month: '01' oa: 1 oa_version: Published Version publication: Nature Communications publication_status: published publisher: Nature Publishing Group publist_id: '5936' pubrep_id: '662' quality_controlled: '1' scopus_import: 1 status: public title: Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 7 year: '2016' ... --- _id: '1342' abstract: - lang: eng text: A key aspect of bacterial survival is the ability to evolve while migrating across spatially varying environmental challenges. Laboratory experiments, however, often study evolution in well-mixed systems. Here, we introduce an experimental device, the microbial evolution and growth arena (MEGA)-plate, in which bacteria spread and evolved on a large antibiotic landscape (120 × 60 centimeters) that allowed visual observation of mutation and selection in a migrating bacterial front.While resistance increased consistently, multiple coexisting lineages diversified both phenotypically and genotypically. Analyzing mutants at and behind the propagating front,we found that evolution is not always led by the most resistant mutants; highly resistant mutants may be trapped behindmore sensitive lineages.TheMEGA-plate provides a versatile platformfor studying microbial adaption and directly visualizing evolutionary dynamics. author: - first_name: Michael full_name: Baym, Michael last_name: Baym - first_name: Tami full_name: Lieberman, Tami last_name: Lieberman - first_name: Eric full_name: Kelsic, Eric last_name: Kelsic - 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: Rotem full_name: Gross, Rotem last_name: Gross - first_name: Idan full_name: Yelin, Idan last_name: Yelin - first_name: Roy full_name: Kishony, Roy last_name: Kishony citation: ama: Baym M, Lieberman T, Kelsic E, et al. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 2016;353(6304):1147-1151. doi:10.1126/science.aag0822 apa: Baym, M., Lieberman, T., Kelsic, E., Chait, R. P., Gross, R., Yelin, I., & Kishony, R. (2016). Spatiotemporal microbial evolution on antibiotic landscapes. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aag0822 chicago: Baym, Michael, Tami Lieberman, Eric Kelsic, Remy P Chait, Rotem Gross, Idan Yelin, and Roy Kishony. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.” Science. American Association for the Advancement of Science, 2016. https://doi.org/10.1126/science.aag0822. ieee: M. Baym et al., “Spatiotemporal microbial evolution on antibiotic landscapes,” Science, vol. 353, no. 6304. American Association for the Advancement of Science, pp. 1147–1151, 2016. ista: Baym M, Lieberman T, Kelsic E, Chait RP, Gross R, Yelin I, Kishony R. 2016. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 353(6304), 1147–1151. mla: Baym, Michael, et al. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.” Science, vol. 353, no. 6304, American Association for the Advancement of Science, 2016, pp. 1147–51, doi:10.1126/science.aag0822. short: M. Baym, T. Lieberman, E. Kelsic, R.P. Chait, R. Gross, I. Yelin, R. Kishony, Science 353 (2016) 1147–1151. date_created: 2018-12-11T11:51:29Z date_published: 2016-09-09T00:00:00Z date_updated: 2021-01-12T06:50:01Z day: '09' department: - _id: CaGu - _id: GaTk doi: 10.1126/science.aag0822 intvolume: ' 353' issue: '6304' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534434/ month: '09' oa: 1 oa_version: Preprint page: 1147 - 1151 publication: Science publication_status: published publisher: American Association for the Advancement of Science publist_id: '5911' quality_controlled: '1' scopus_import: 1 status: public title: Spatiotemporal microbial evolution on antibiotic landscapes type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 353 year: '2016' ... --- _id: '1349' abstract: - lang: eng text: Crossing fitness valleys is one of the major obstacles to function optimization. In this paper we investigate how the structure of the fitness valley, namely its depth d and length ℓ, influence the runtime of different strategies for crossing these valleys. We present a runtime comparison between the (1+1) EA and two non-elitist nature-inspired algorithms, Strong Selection Weak Mutation (SSWM) and the Metropolis algorithm. While the (1+1) EA has to jump across the valley to a point of higher fitness because it does not accept decreasing moves, the non-elitist algorithms may cross the valley by accepting worsening moves. We show that while the runtime of the (1+1) EA algorithm depends critically on the length of the valley, the runtimes of the non-elitist algorithms depend crucially only on the depth of the valley. In particular, the expected runtime of both SSWM and Metropolis is polynomial in ℓ and exponential in d while the (1+1) EA is efficient only for valleys of small length. Moreover, we show that both SSWM and Metropolis can also efficiently optimize a rugged function consisting of consecutive valleys. author: - first_name: Pietro full_name: Oliveto, Pietro last_name: Oliveto - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Jorge full_name: Heredia, Jorge last_name: Heredia - first_name: Dirk full_name: Sudholt, Dirk last_name: Sudholt - first_name: Barbora full_name: Trubenova, Barbora id: 42302D54-F248-11E8-B48F-1D18A9856A87 last_name: Trubenova orcid: 0000-0002-6873-2967 citation: ama: 'Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. When non-elitism outperforms elitism for crossing fitness valleys. In: Proceedings of the Genetic and Evolutionary Computation Conference 2016 . ACM; 2016:1163-1170. doi:10.1145/2908812.2908909' apa: 'Oliveto, P., Paixao, T., Heredia, J., Sudholt, D., & Trubenova, B. (2016). When non-elitism outperforms elitism for crossing fitness valleys. In Proceedings of the Genetic and Evolutionary Computation Conference 2016 (pp. 1163–1170). Denver, CO, USA: ACM. https://doi.org/10.1145/2908812.2908909' chicago: Oliveto, Pietro, Tiago Paixao, Jorge Heredia, Dirk Sudholt, and Barbora Trubenova. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.” In Proceedings of the Genetic and Evolutionary Computation Conference 2016 , 1163–70. ACM, 2016. https://doi.org/10.1145/2908812.2908909. ieee: P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, and B. Trubenova, “When non-elitism outperforms elitism for crossing fitness valleys,” in Proceedings of the Genetic and Evolutionary Computation Conference 2016 , Denver, CO, USA, 2016, pp. 1163–1170. ista: 'Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. 2016. When non-elitism outperforms elitism for crossing fitness valleys. Proceedings of the Genetic and Evolutionary Computation Conference 2016 . GECCO: Genetic and evolutionary computation conference, 1163–1170.' mla: Oliveto, Pietro, et al. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.” Proceedings of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–70, doi:10.1145/2908812.2908909. short: P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, B. Trubenova, in:, Proceedings of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–1170. conference: end_date: 2016-07-24 location: Denver, CO, USA name: 'GECCO: Genetic and evolutionary computation conference' start_date: 2016-07-20 date_created: 2018-12-11T11:51:31Z date_published: 2016-07-20T00:00:00Z date_updated: 2021-01-12T06:50:03Z day: '20' ddc: - '576' department: - _id: NiBa - _id: CaGu doi: 10.1145/2908812.2908909 ec_funded: 1 file: - access_level: open_access checksum: a1896e39e4113f2711e46b435d5f3e69 content_type: application/pdf creator: system date_created: 2018-12-12T10:16:27Z date_updated: 2020-07-14T12:44:45Z file_id: '5214' file_name: IST-2016-650-v1+1_p1163-oliveto.pdf file_size: 979026 relation: main_file file_date_updated: 2020-07-14T12:44:45Z has_accepted_license: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: 1163 - 1170 project: - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation publication: 'Proceedings of the Genetic and Evolutionary Computation Conference 2016 ' publication_status: published publisher: ACM publist_id: '5900' pubrep_id: '650' quality_controlled: '1' scopus_import: 1 status: public title: When non-elitism outperforms elitism for crossing fitness valleys 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: conference user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 year: '2016' ... --- _id: '1359' abstract: - lang: eng text: "The role of gene interactions in the evolutionary process has long\r\nbeen controversial. Although some argue that they are not of\r\nimportance, because most variation is additive, others claim that\r\ntheir effect in the long term can be substantial. Here, we focus on\r\nthe long-term effects of genetic interactions under directional\r\nselection assuming no mutation or dominance, and that epistasis is\r\nsymmetrical overall. We ask by how much the mean of a complex\r\ntrait can be increased by selection and analyze two extreme\r\nregimes, in which either drift or selection dominate the dynamics\r\nof allele frequencies. In both scenarios, epistatic interactions affect\r\nthe long-term response to selection by modulating the additive\r\ngenetic variance. When drift dominates, we extend Robertson\r\n’\r\ns\r\n[Robertson A (1960)\r\nProc R Soc Lond B Biol Sci\r\n153(951):234\r\n−\r\n249]\r\nargument to show that, for any form of epistasis, the total response\r\nof a haploid population is proportional to the initial total genotypic\r\nvariance. In contrast, the total response of a diploid population is\r\nincreased by epistasis, for a given initial genotypic variance. When\r\nselection dominates, we show that the total selection response can\r\nonly be increased by epistasis when s\r\nome initially deleterious alleles\r\nbecome favored as the genetic background changes. We find a sim-\r\nple approximation for this effect and show that, in this regime, it is\r\nthe structure of the genotype - phenotype map that matters and not\r\nthe variance components of the population." article_processing_charge: No article_type: original author: - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 citation: ama: Paixao T, Barton NH. The effect of gene interactions on the long-term response to selection. PNAS. 2016;113(16):4422-4427. doi:10.1073/pnas.1518830113 apa: Paixao, T., & Barton, N. H. (2016). The effect of gene interactions on the long-term response to selection. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1518830113 chicago: Paixao, Tiago, and Nicholas H Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS. National Academy of Sciences, 2016. https://doi.org/10.1073/pnas.1518830113. ieee: T. Paixao and N. H. Barton, “The effect of gene interactions on the long-term response to selection,” PNAS, vol. 113, no. 16. National Academy of Sciences, pp. 4422–4427, 2016. ista: Paixao T, Barton NH. 2016. The effect of gene interactions on the long-term response to selection. PNAS. 113(16), 4422–4427. mla: Paixao, Tiago, and Nicholas H. Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS, vol. 113, no. 16, National Academy of Sciences, 2016, pp. 4422–27, doi:10.1073/pnas.1518830113. short: T. Paixao, N.H. Barton, PNAS 113 (2016) 4422–4427. date_created: 2018-12-11T11:51:34Z date_published: 2016-04-19T00:00:00Z date_updated: 2021-01-12T06:50:08Z day: '19' department: - _id: NiBa - _id: CaGu doi: 10.1073/pnas.1518830113 ec_funded: 1 external_id: pmid: - '27044080' intvolume: ' 113' issue: '16' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843425/ month: '04' oa: 1 oa_version: Published Version page: 4422 - 4427 pmid: 1 project: - _id: 25B07788-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '250152' name: Limits to selection in biology and in evolutionary computation - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation publication: PNAS publication_status: published publisher: National Academy of Sciences publist_id: '5886' quality_controlled: '1' scopus_import: 1 status: public title: The effect of gene interactions on the long-term response to selection type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 113 year: '2016' ... --- _id: '1427' abstract: - lang: eng text: Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner. author: - first_name: Mato full_name: Lagator, Mato id: 345D25EC-F248-11E8-B48F-1D18A9856A87 last_name: Lagator - first_name: Claudia full_name: Igler, Claudia id: 46613666-F248-11E8-B48F-1D18A9856A87 last_name: Igler - first_name: Anaisa full_name: Moreno, Anaisa last_name: Moreno - 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: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 citation: ama: Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 2016;33(3):761-769. doi:10.1093/molbev/msv269 apa: Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016). Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269 chicago: Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv269. ieee: M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic interactions in the arabinose cis-regulatory element,” Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press, pp. 761–769, 2016. ista: Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. 2016. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 33(3), 761–769. mla: Lagator, Mato, et al. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University Press, 2016, pp. 761–69, doi:10.1093/molbev/msv269. short: M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769. date_created: 2018-12-11T11:51:57Z date_published: 2016-03-01T00:00:00Z date_updated: 2021-01-12T06:50:39Z day: '01' ddc: - '570' - '576' department: - _id: CaGu - _id: JoBo doi: 10.1093/molbev/msv269 ec_funded: 1 file: - access_level: open_access checksum: 1f456ce1d2aa2f67176a1709f9702ecf content_type: application/pdf creator: system date_created: 2018-12-12T10:09:27Z date_updated: 2020-07-14T12:44:53Z file_id: '4751' file_name: IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf file_size: 648115 relation: main_file file_date_updated: 2020-07-14T12:44:53Z has_accepted_license: '1' intvolume: ' 33' issue: '3' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 761 - 769 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Molecular Biology and Evolution publication_status: published publisher: Oxford University Press publist_id: '5772' pubrep_id: '588' quality_controlled: '1' scopus_import: 1 status: public title: Epistatic interactions in the arabinose cis-regulatory element tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 33 year: '2016' ... --- _id: '1524' abstract: - lang: eng text: "When designing genetic circuits, the typical primitives used in major existing modelling formalisms are gene interaction graphs, where edges between genes denote either an activation or inhibition relation. However, when designing experiments, it is important to be precise about the low-level mechanistic details as to how each such relation is implemented. The rule-based modelling language Kappa allows to unambiguously specify mechanistic details such as DNA binding sites, dimerisation of transcription factors, or co-operative interactions. Such a detailed description comes with complexity and computationally costly executions. We propose a general method for automatically transforming a rule-based program, by eliminating intermediate species and adjusting the rate constants accordingly. To the best of our knowledge, we show the first automated reduction of rule-based models based on equilibrium approximations.\r\nOur algorithm is an adaptation of an existing algorithm, which was designed for reducing reaction-based programs; our version of the algorithm scans the rule-based Kappa model in search for those interaction patterns known to be amenable to equilibrium approximations (e.g. Michaelis-Menten scheme). Additional checks are then performed in order to verify if the reduction is meaningful in the context of the full model. The reduced model is efficiently obtained by static inspection over the rule-set. The tool is tested on a detailed rule-based model of a λ-phage switch, which lists 92 rules and 13 agents. The reduced model has 11 rules and 5 agents, and provides a dramatic reduction in simulation time of several orders of magnitude." acknowledgement: This research was supported by the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 291734, and the SNSF Early Postdoc.Mobility Fellowship, the grant number P2EZP2_148797. alternative_title: - LNCS author: - first_name: Andreea full_name: Beica, Andreea last_name: Beica - 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: Tatjana full_name: Petrov, Tatjana id: 3D5811FC-F248-11E8-B48F-1D18A9856A87 last_name: Petrov orcid: 0000-0002-9041-0905 citation: ama: 'Beica A, Guet CC, Petrov T. Efficient reduction of kappa models by static inspection of the rule-set. In: Vol 9271. Springer; 2016:173-191. doi:10.1007/978-3-319-26916-0_10' apa: 'Beica, A., Guet, C. C., & Petrov, T. (2016). Efficient reduction of kappa models by static inspection of the rule-set (Vol. 9271, pp. 173–191). Presented at the HSB: Hybrid Systems Biology, Madrid, Spain: Springer. https://doi.org/10.1007/978-3-319-26916-0_10' chicago: Beica, Andreea, Calin C Guet, and Tatjana Petrov. “Efficient Reduction of Kappa Models by Static Inspection of the Rule-Set,” 9271:173–91. Springer, 2016. https://doi.org/10.1007/978-3-319-26916-0_10. ieee: 'A. Beica, C. C. Guet, and T. Petrov, “Efficient reduction of kappa models by static inspection of the rule-set,” presented at the HSB: Hybrid Systems Biology, Madrid, Spain, 2016, vol. 9271, pp. 173–191.' ista: 'Beica A, Guet CC, Petrov T. 2016. Efficient reduction of kappa models by static inspection of the rule-set. HSB: Hybrid Systems Biology, LNCS, vol. 9271, 173–191.' mla: Beica, Andreea, et al. Efficient Reduction of Kappa Models by Static Inspection of the Rule-Set. Vol. 9271, Springer, 2016, pp. 173–91, doi:10.1007/978-3-319-26916-0_10. short: A. Beica, C.C. Guet, T. Petrov, in:, Springer, 2016, pp. 173–191. conference: end_date: 2015-09-05 location: Madrid, Spain name: 'HSB: Hybrid Systems Biology' start_date: 2015-09-04 date_created: 2018-12-11T11:52:31Z date_published: 2016-01-10T00:00:00Z date_updated: 2021-01-12T06:51:22Z day: '10' department: - _id: CaGu - _id: ToHe doi: 10.1007/978-3-319-26916-0_10 ec_funded: 1 intvolume: ' 9271' language: - iso: eng main_file_link: - open_access: '1' url: http://arxiv.org/abs/1501.00440 month: '01' oa: 1 oa_version: Preprint page: 173 - 191 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication_status: published publisher: Springer publist_id: '5649' quality_controlled: '1' scopus_import: 1 status: public title: Efficient reduction of kappa models by static inspection of the rule-set type: conference user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 9271 year: '2016' ... --- _id: '1250' abstract: - lang: eng text: In bacteria, replicative aging manifests as a difference in growth or survival between the two cells emerging from division. One cell can be regarded as an aging mother with a decreased potential for future survival and division, the other as a rejuvenated daughter. Here, we aimed at investigating some of the processes involved in aging in the bacterium Escherichia coli, where the two types of cells can be distinguished by the age of their cell poles. We found that certain changes in the regulation of the carbohydrate metabolism can affect aging. A mutation in the carbon storage regulator gene, csrA, leads to a dramatically shorter replicative lifespan; csrA mutants stop dividing once their pole exceeds an age of about five divisions. These old-pole cells accumulate glycogen at their old cell poles; after their last division, they do not contain a chromosome, presumably because of spatial exclusion by the glycogen aggregates. The new-pole daughters produced by these aging mothers are born young; they only express the deleterious phenotype once their pole is old. These results demonstrate how manipulations of nutrient allocation can lead to the exclusion of the chromosome and limit replicative lifespan in E. coli, and illustrate how mutations can have phenotypic effects that are specific for cells with old poles. This raises the question how bacteria can avoid the accumulation of such mutations in their genomes over evolutionary times, and how they can achieve the long replicative lifespans that have recently been reported. acknowledgement: This manuscript is dedicated to the memory of Alex Böhm, who was a great friend and a passionate biologist. Alex passed away after the initial submission of this manuscript. We thank Vesna Olivera and Ursula Sauder from the Zentrum für Mikroskopie Uni Basel for excellent service, and Olin Silander, Nikki Freed, and Nela Nikolic for helpful discussions. This work was supported by the Swiss National Science Foundation grants to M. Ackermann and Urs Jenal (supporting AB). article_number: e1005974 author: - first_name: Alex full_name: Boehm, Alex last_name: Boehm - first_name: Markus full_name: Arnoldini, Markus last_name: Arnoldini - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Thomas full_name: Röösli, Thomas last_name: Röösli - first_name: Colette full_name: Bigosch, Colette last_name: Bigosch - first_name: Martin full_name: Ackermann, Martin last_name: Ackermann citation: ama: Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. 2016;12(4). doi:10.1371/journal.pgen.1005974 apa: Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann, M. (2016). Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974 chicago: Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette Bigosch, and Martin Ackermann. “Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E Coli.” PLoS Genetics. Public Library of Science, 2016. https://doi.org/10.1371/journal.pgen.1005974. ieee: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann, “Genetic manipulation of glycogen allocation affects replicative lifespan in E coli,” PLoS Genetics, vol. 12, no. 4. Public Library of Science, 2016. ista: Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016. Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. 12(4), e1005974. mla: Boehm, Alex, et al. “Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E Coli.” PLoS Genetics, vol. 12, no. 4, e1005974, Public Library of Science, 2016, doi:10.1371/journal.pgen.1005974. short: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, PLoS Genetics 12 (2016). date_created: 2018-12-11T11:50:56Z date_published: 2016-04-19T00:00:00Z date_updated: 2023-02-23T14:11:39Z day: '19' ddc: - '576' - '579' department: - _id: CaGu doi: 10.1371/journal.pgen.1005974 file: - access_level: open_access checksum: 53d22b2b39e5adc243d34f18b2615a85 content_type: application/pdf creator: system date_created: 2018-12-12T10:14:17Z date_updated: 2020-07-14T12:44:41Z file_id: '5067' file_name: IST-2016-705-v1+1_journal.pgen.1005974.PDF file_size: 6273249 relation: main_file file_date_updated: 2020-07-14T12:44:41Z has_accepted_license: '1' intvolume: ' 12' issue: '4' language: - iso: eng month: '04' oa: 1 oa_version: Published Version publication: PLoS Genetics publication_status: published publisher: Public Library of Science publist_id: '6077' pubrep_id: '705' quality_controlled: '1' related_material: record: - id: '9873' relation: research_data status: public scopus_import: 1 status: public title: Genetic manipulation of glycogen allocation affects replicative lifespan in E coli tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 12 year: '2016' ... --- _id: '9873' article_processing_charge: No author: - first_name: Alex full_name: Boehm, Alex last_name: Boehm - first_name: Markus full_name: Arnoldini, Markus last_name: Arnoldini - first_name: Tobias full_name: Bergmiller, Tobias id: 2C471CFA-F248-11E8-B48F-1D18A9856A87 last_name: Bergmiller orcid: 0000-0001-5396-4346 - first_name: Thomas full_name: Röösli, Thomas last_name: Röösli - first_name: Colette full_name: Bigosch, Colette last_name: Bigosch - first_name: Martin full_name: Ackermann, Martin last_name: Ackermann citation: ama: Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Quantification of the growth rate reduction as a consequence of age-specific mortality. 2016. doi:10.1371/journal.pgen.1005974.s015 apa: Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann, M. (2016). Quantification of the growth rate reduction as a consequence of age-specific mortality. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974.s015 chicago: Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette Bigosch, and Martin Ackermann. “Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality.” Public Library of Science, 2016. https://doi.org/10.1371/journal.pgen.1005974.s015. ieee: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann, “Quantification of the growth rate reduction as a consequence of age-specific mortality.” Public Library of Science, 2016. ista: Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016. Quantification of the growth rate reduction as a consequence of age-specific mortality, Public Library of Science, 10.1371/journal.pgen.1005974.s015. mla: Boehm, Alex, et al. Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality. Public Library of Science, 2016, doi:10.1371/journal.pgen.1005974.s015. short: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, (2016). date_created: 2021-08-10T09:42:34Z date_updated: 2023-02-21T16:50:13Z day: '19' department: - _id: CaGu doi: 10.1371/journal.pgen.1005974.s015 month: '04' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '1250' relation: used_in_publication status: public status: public title: Quantification of the growth rate reduction as a consequence of age-specific mortality type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2016' ...