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(2023). <i>Adaptive mutation in E. coli modulated by luxS</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:14641\">https://doi.org/10.15479/at:ista:14641</a>","mla":"Hennessey-Wesen, Mike. <i>Adaptive Mutation in E. Coli Modulated by LuxS</i>. Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/at:ista:14641\">10.15479/at:ista:14641</a>.","ama":"Hennessey-Wesen M. Adaptive mutation in E. coli modulated by luxS. 2023. doi:<a href=\"https://doi.org/10.15479/at:ista:14641\">10.15479/at:ista:14641</a>","ista":"Hennessey-Wesen M. 2023. Adaptive mutation in E. coli modulated by luxS. Institute of Science and Technology Austria.","short":"M. Hennessey-Wesen, Adaptive Mutation in E. Coli Modulated by LuxS, Institute of Science and Technology Austria, 2023."},"has_accepted_license":"1","language":[{"iso":"eng"}],"OA_place":"publisher","article_processing_charge":"No","date_updated":"2026-04-07T13:29:59Z","_id":"14641","abstract":[{"text":"Mutation rates represent the net result of complex interactions among various\r\ncellular processes and can dramatically influence the evolutionary fate of\r\nmicrobial populations. However, many popular techniques used to study\r\nmutations are subject to the confounding effects of heredity and the subtleties\r\nof adaptation to selection, all of which make it difficult to observe any dynamic\r\nresponses of mutation rates to fitness challenges. Furthermore, in spite of the\r\nubiquity of quorum sensing systems across the bacterial domain and relevance\r\nfor many physiological behaviors, the effects of such mechanisms on mutation\r\nrate and adaptation remain poorly understood. In the following work, I\r\npresent the development of a microfluidic droplet-based method to measure\r\nsingle base-pair mutation rates in growing populations of the bacterium\r\nEscherichia coli. I use this method to observe a stress-induced increase in\r\nmutation rate that is mediated by luxS, a highly conserved bacterial quorum\r\nsensing component. I also show that the aforementioned increase in mutation\r\nrate, and its associated control by luxS, corresponds to a higher degree of\r\nadaptability under competitive environments.","lang":"eng"}],"date_created":"2023-12-04T13:17:37Z","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"CampIT"}],"file":[{"file_size":46405919,"checksum":"4127c285b34f4bf7fb31ef24f9d14c25","file_id":"14648","relation":"source_file","date_updated":"2024-11-30T23:30:05Z","access_level":"closed","creator":"mhenness","date_created":"2023-12-06T13:13:26Z","embargo_to":"open_access","content_type":"application/vnd.oasis.opendocument.text","file_name":"mike_thesis_v06-12-2023.odt"},{"embargo":"2026-07-18","file_name":"mike_thesis_v06-12-2023.pdf","date_created":"2023-12-06T13:14:15Z","content_type":"application/pdf","embargo_to":"open_access","creator":"mhenness","access_level":"closed","date_updated":"2025-07-17T11:20:25Z","relation":"main_file","file_id":"14649","checksum":"f5203a61eddaf35235bbc51904d73982","file_size":21282155},{"file_id":"19720","file_size":45847968,"checksum":"902102d26d30e74dbd6cdd70a65820c3","date_updated":"2025-05-20T22:31:34Z","creator":"cchlebak","access_level":"closed","relation":"other","title":"Print version","description":"for printing purposes only","content_type":"application/pdf","embargo_to":"open_access","date_created":"2025-05-20T12:59:12Z","file_name":"2023_Hennessey_Michael_Thesis_print.pdf"}],"keyword":["microfluidics","miceobiology","mutations","quorum sensing"],"type":"dissertation","corr_author":"1","status":"public","year":"2023","doi":"10.15479/at:ista:14641","project":[{"grant_number":"665385","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program"}],"author":[{"last_name":"Hennessey-Wesen","first_name":"Mike","id":"3F338C72-F248-11E8-B48F-1D18A9856A87","full_name":"Hennessey-Wesen, Mike"}],"page":"104","day":"30","ddc":["570"],"degree_awarded":"PhD","month":"11","title":"Adaptive mutation in E. coli modulated by luxS"},{"corr_author":"1","publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","date_published":"2020-01-28T00:00:00Z","status":"public","abstract":[{"lang":"eng","text":"Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature."}],"date_created":"2020-01-28T10:41:49Z","file_date_updated":"2020-07-14T12:47:57Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","keyword":["Matlab scripts","analysis of microfluidics","mathematical model"],"file":[{"relation":"main_file","date_updated":"2020-07-14T12:47:57Z","access_level":"open_access","creator":"rgrah","file_size":73363365,"checksum":"9d292cf5207b3829225f44c044cdb3fd","file_id":"7384","content_type":"application/zip","date_created":"2020-01-28T10:39:40Z","file_name":"Scripts.zip"},{"date_updated":"2020-07-14T12:47:57Z","access_level":"open_access","creator":"rgrah","relation":"main_file","file_id":"7385","file_size":962,"checksum":"4076ceab32ef588cc233802bab24c1ab","content_type":"text/plain","date_created":"2020-01-28T10:39:30Z","file_name":"READ_ME_MAIN.txt"}],"oa":1,"type":"research_data","related_material":{"record":[{"id":"7652","status":"public","relation":"used_in_publication"}]},"date_updated":"2025-06-12T07:34:12Z","article_processing_charge":"No","month":"01","_id":"7383","title":"Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation","author":[{"id":"483E70DE-F248-11E8-B48F-1D18A9856A87","full_name":"Grah, Rok","orcid":"0000-0003-2539-3560","last_name":"Grah","first_name":"Rok"}],"year":"2020","doi":"10.15479/AT:ISTA:7383","day":"28","citation":{"short":"R. Grah, (2020).","ista":"Grah R. 2020. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:7383\">10.15479/AT:ISTA:7383</a>.","mla":"Grah, Rok. <i>Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7383\">10.15479/AT:ISTA:7383</a>.","ama":"Grah R. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7383\">10.15479/AT:ISTA:7383</a>","apa":"Grah, R. (2020). Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7383\">https://doi.org/10.15479/AT:ISTA:7383</a>","ieee":"R. Grah, “Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation.” Institute of Science and Technology Austria, 2020.","chicago":"Grah, Rok. “Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:7383\">https://doi.org/10.15479/AT:ISTA:7383</a>."},"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"contributor":[{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","contributor_type":"project_leader","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052"}],"has_accepted_license":"1"},{"abstract":[{"text":"Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature.","lang":"eng"}],"date_created":"2019-11-13T09:07:31Z","file_date_updated":"2020-07-14T12:47:47Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","keyword":["Escherichia coli","gene amplification","galactose","DOG","experimental evolution","Illumina sequence data","FACS data","microfluidics data"],"oa":1,"file":[{"file_name":"D8_S35_R2_001.fastq","date_created":"2019-11-13T08:52:21Z","content_type":"application/octet-stream","description":"Illumina whole genome sequence data for Locus 1 - amplified.","checksum":"72441055043eda4cbf1398a422e2c118","file_size":2456192500,"file_id":"7017","title":"Locus1_amplified","relation":"main_file","access_level":"open_access","creator":"itomanek","date_updated":"2020-07-14T12:47:47Z"},{"date_updated":"2020-07-14T12:47:47Z","creator":"itomanek","access_level":"open_access","relation":"main_file","title":"Locus1_ancestral","file_id":"7018","file_size":2833452234,"checksum":"a4ac50bf655d9c751f0305ade5c2ee16","description":"Illumina whole genome sequence data for Locus 1 - 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see read_me_microfluidics"}],"type":"research_data","publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","date_published":"2019-11-13T00:00:00Z","status":"public","author":[{"id":"3981F020-F248-11E8-B48F-1D18A9856A87","full_name":"Tomanek, Isabella","orcid":"0000-0001-6197-363X","first_name":"Isabella","last_name":"Tomanek"}],"year":"2019","doi":"10.15479/AT:ISTA:7016","day":"13","citation":{"mla":"Tomanek, Isabella. <i>Data for the Paper “Gene Amplification as a Form of Population-Level Gene Expression Regulation.”</i> Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7016\">10.15479/AT:ISTA:7016</a>.","ama":"Tomanek I. Data for the paper “Gene amplification as a form of population-level gene expression regulation.” 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7016\">10.15479/AT:ISTA:7016</a>","short":"I. Tomanek, (2019).","ista":"Tomanek I. 2019. Data for the paper ‘Gene amplification as a form of population-level gene expression regulation’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:7016\">10.15479/AT:ISTA:7016</a>.","apa":"Tomanek, I. (2019). Data for the paper “Gene amplification as a form of population-level gene expression regulation.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7016\">https://doi.org/10.15479/AT:ISTA:7016</a>","chicago":"Tomanek, Isabella. “Data for the Paper ‘Gene Amplification as a Form of Population-Level Gene Expression Regulation.’” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:7016\">https://doi.org/10.15479/AT:ISTA:7016</a>.","ieee":"I. Tomanek, “Data for the paper ‘Gene amplification as a form of population-level gene expression regulation.’” Institute of Science and Technology Austria, 2019."},"department":[{"_id":"CaGu"}],"contributor":[{"first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","contributor_type":"project_leader","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"has_accepted_license":"1","ddc":["576"],"related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"7652"}]},"date_updated":"2025-06-12T07:34:12Z","month":"11","article_processing_charge":"No","_id":"7016","title":"Data for the paper \"Gene amplification as a form of population-level gene expression regulation\""},{"day":"24","page":"171","project":[{"name":"Nano-Analytics of Cellular Systems","_id":"265E2996-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W01250-B20"}],"author":[{"id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","full_name":"Kopf, Aglaja","last_name":"Kopf","first_name":"Aglaja","orcid":"0000-0002-2187-6656"}],"doi":"10.15479/AT:ISTA:6891","year":"2019","title":"The implication of cytoskeletal dynamics on leukocyte migration","month":"07","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"6877"},{"relation":"part_of_dissertation","status":"public","id":"15"},{"relation":"part_of_dissertation","status":"public","id":"6328"}],"link":[{"url":"https://ist.ac.at/en/news/feeling-like-a-cell/","relation":"press_release"}]},"degree_awarded":"PhD","ddc":["570"],"type":"dissertation","keyword":["cell biology","immunology","leukocyte","migration","microfluidics"],"oa":1,"file":[{"checksum":"00d100d6468e31e583051e0a006b640c","file_size":74735267,"file_id":"6950","relation":"source_file","access_level":"closed","creator":"akopf","date_updated":"2020-10-17T22:30:03Z","file_name":"Kopf_PhD_Thesis.docx","date_created":"2019-10-15T05:28:42Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access"},{"date_created":"2019-10-15T05:28:47Z","content_type":"application/pdf","file_name":"Kopf_PhD_Thesis1.pdf","embargo":"2020-10-16","relation":"main_file","date_updated":"2020-10-17T22:30:03Z","creator":"akopf","access_level":"open_access","file_size":52787224,"checksum":"5d1baa899993ae6ca81aebebe1797000","file_id":"6951"}],"date_created":"2019-09-19T08:19:44Z","abstract":[{"text":"While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. \r\nCells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. \r\nNevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. \r\nTherefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. \r\nThe results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. \r\nThus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. \r\nThereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance.\r\n","lang":"eng"}],"status":"public","corr_author":"1","OA_place":"publisher","language":[{"iso":"eng"}],"has_accepted_license":"1","publication_identifier":{"eissn":["2663-337X"],"isbn":["978-3-99078-002-2"]},"citation":{"chicago":"Kopf, Aglaja. “The Implication of Cytoskeletal Dynamics on Leukocyte Migration.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6891\">https://doi.org/10.15479/AT:ISTA:6891</a>.","ieee":"A. Kopf, “The implication of cytoskeletal dynamics on leukocyte migration,” Institute of Science and Technology Austria, 2019.","ama":"Kopf A. The implication of cytoskeletal dynamics on leukocyte migration. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6891\">10.15479/AT:ISTA:6891</a>","mla":"Kopf, Aglaja. <i>The Implication of Cytoskeletal Dynamics on Leukocyte Migration</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6891\">10.15479/AT:ISTA:6891</a>.","short":"A. Kopf, The Implication of Cytoskeletal Dynamics on Leukocyte Migration, Institute of Science and Technology Austria, 2019.","ista":"Kopf A. 2019. The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria.","apa":"Kopf, A. (2019). <i>The implication of cytoskeletal dynamics on leukocyte migration</i>. 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