[{"day":"01","publication":"PNAS","language":[{"iso":"eng"}],"year":"2015","publication_status":"published","volume":112,"doi":"10.1073/pnas.1510282112","issue":"48","date_published":"2015-12-01T00:00:00Z","date_created":"2018-12-11T11:52:47Z","page":"14906 - 14911","oa_version":"None","acknowledgement":"This work is part of the research program of the Foundation for Fundamental Research on Matter, which is part of the Netherlands Organization for Scientific Research (NWO). M.G.J.d.V. was (partially) funded by NWO Earth and Life Sciences (ALW), project 863.14.015. We thank D. M. Weinreich, J. A. G. M. de Visser, T. Paixão, J. Polechová, T. Friedlander, and A. E. Mayo for reading and commenting on earlier versions of the manuscript and B. Houchmandzadeh, O. Rivoire, and M. Hemery for discussions and suggestions on the Markov computation. Furthermore, we thank F. J. Poelwijk for sharing plasmid pCascade5 and pRD007 and Y. Yokobayashi for sharing plasmid pINV-110. We also thank the anonymous reviewers for remarks on the initial version of the manuscript.","abstract":[{"lang":"eng","text":"Epistatic interactions can frustrate and shape evolutionary change. Indeed, phenotypes may fail to evolve when essential mutations are only accessible through positive selection if they are fixed simultaneously. How environmental variability affects such constraints is poorly understood. Here, we studied genetic constraints in fixed and fluctuating environments using the Escherichia coli lac operon as a model system for genotype-environment interactions. We found that, in different fixed environments, all trajectories that were reconstructed by applying point mutations within the transcription factor-operator interface became trapped at suboptima, where no additional improvements were possible. Paradoxically, repeated switching between these same environments allows unconstrained adaptation by continuous improvements. This evolutionary mode is explained by pervasive cross-environmental tradeoffs that reposition the peaks in such a way that trapped genotypes can repeatedly climb ascending slopes and hence, escape adaptive stasis. Using a Markov approach, we developed a mathematical framework to quantify the landscape-crossing rates and show that this ratchet-like adaptive mechanism is robust in a wide spectrum of fluctuating environments. Overall, this study shows that genetic constraints can be overcome by environmental change and that crossenvironmental tradeoffs do not necessarily impede but also, can facilitate adaptive evolution. Because tradeoffs and environmental variability are ubiquitous in nature, we speculate this evolutionary mode to be of general relevance."}],"month":"12","intvolume":" 112","quality_controlled":"1","scopus_import":1,"publisher":"National Academy of Sciences","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"de Vos, Marjon, et al. “Breaking Evolutionary Constraint with a Tradeoff Ratchet.” PNAS, vol. 112, no. 48, National Academy of Sciences, 2015, pp. 14906–11, doi:10.1073/pnas.1510282112.","short":"M. de Vos, A. Dawid, V. Šunderlíková, S. Tans, PNAS 112 (2015) 14906–14911.","ieee":"M. de Vos, A. Dawid, V. Šunderlíková, and S. Tans, “Breaking evolutionary constraint with a tradeoff ratchet,” PNAS, vol. 112, no. 48. National Academy of Sciences, pp. 14906–14911, 2015.","ama":"de Vos M, Dawid A, Šunderlíková V, Tans S. Breaking evolutionary constraint with a tradeoff ratchet. PNAS. 2015;112(48):14906-14911. doi:10.1073/pnas.1510282112","apa":"de Vos, M., Dawid, A., Šunderlíková, V., & Tans, S. (2015). Breaking evolutionary constraint with a tradeoff ratchet. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1510282112","chicago":"Vos, Marjon de, Alexandre Dawid, Vanda Šunderlíková, and Sander Tans. “Breaking Evolutionary Constraint with a Tradeoff Ratchet.” PNAS. National Academy of Sciences, 2015. https://doi.org/10.1073/pnas.1510282112.","ista":"de Vos M, Dawid A, Šunderlíková V, Tans S. 2015. Breaking evolutionary constraint with a tradeoff ratchet. PNAS. 112(48), 14906–14911."},"date_updated":"2021-01-12T06:51:40Z","title":"Breaking evolutionary constraint with a tradeoff ratchet","department":[{"_id":"ToBo"}],"author":[{"id":"3111FFAC-F248-11E8-B48F-1D18A9856A87","first_name":"Marjon","last_name":"De Vos","full_name":"De Vos, Marjon"},{"first_name":"Alexandre","full_name":"Dawid, Alexandre","last_name":"Dawid"},{"first_name":"Vanda","last_name":"Šunderlíková","full_name":"Šunderlíková, Vanda"},{"full_name":"Tans, Sander","last_name":"Tans","first_name":"Sander"}],"publist_id":"5600","_id":"1571","status":"public","type":"journal_article"},{"publication_status":"published","year":"2015","language":[{"iso":"eng"}],"publication":"Cell","day":"23","page":"431 - 432","date_created":"2018-12-11T11:52:50Z","doi":"10.1016/j.cell.2015.04.009","issue":"3","date_published":"2015-04-23T00:00:00Z","volume":161,"abstract":[{"text":"In animal embryos, morphogen gradients determine tissue patterning and morphogenesis. Shyer et al. provide evidence that, during vertebrate gut formation, tissue folding generates graded activity of signals required for subsequent steps of gut growth and differentiation, thereby revealing an intriguing link between tissue morphogenesis and morphogen gradient formation.","lang":"eng"}],"oa_version":"None","quality_controlled":"1","scopus_import":"1","publisher":"Cell Press","intvolume":" 161","month":"04","citation":{"ieee":"M. T. Bollenbach and C.-P. J. Heisenberg, “Gradients are shaping up,” Cell, vol. 161, no. 3. Cell Press, pp. 431–432, 2015.","short":"M.T. Bollenbach, C.-P.J. Heisenberg, Cell 161 (2015) 431–432.","ama":"Bollenbach MT, Heisenberg C-PJ. Gradients are shaping up. Cell. 2015;161(3):431-432. doi:10.1016/j.cell.2015.04.009","apa":"Bollenbach, M. T., & Heisenberg, C.-P. J. (2015). Gradients are shaping up. Cell. Cell Press. https://doi.org/10.1016/j.cell.2015.04.009","mla":"Bollenbach, Mark Tobias, and Carl-Philipp J. Heisenberg. “Gradients Are Shaping Up.” Cell, vol. 161, no. 3, Cell Press, 2015, pp. 431–32, doi:10.1016/j.cell.2015.04.009.","ista":"Bollenbach MT, Heisenberg C-PJ. 2015. Gradients are shaping up. Cell. 161(3), 431–432.","chicago":"Bollenbach, Mark Tobias, and Carl-Philipp J Heisenberg. “Gradients Are Shaping Up.” Cell. Cell Press, 2015. https://doi.org/10.1016/j.cell.2015.04.009."},"date_updated":"2022-08-25T13:56:10Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","author":[{"last_name":"Bollenbach","full_name":"Bollenbach, Mark Tobias","orcid":"0000-0003-4398-476X","first_name":"Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J"}],"publist_id":"5590","title":"Gradients are shaping up","department":[{"_id":"ToBo"},{"_id":"CaHe"}],"_id":"1581","type":"journal_article","status":"public"},{"date_updated":"2021-01-12T06:51:46Z","citation":{"chicago":"Angermayr, Andreas, Aleix Gorchs, and Klaas Hellingwerf. “Metabolic Engineering of Cyanobacteria for the Synthesis of Commodity Products.” Trends in Biotechnology. Elsevier, 2015. https://doi.org/10.1016/j.tibtech.2015.03.009.","ista":"Angermayr A, Gorchs A, Hellingwerf K. 2015. Metabolic engineering of cyanobacteria for the synthesis of commodity products. Trends in Biotechnology. 33(6), 352–361.","mla":"Angermayr, Andreas, et al. “Metabolic Engineering of Cyanobacteria for the Synthesis of Commodity Products.” Trends in Biotechnology, vol. 33, no. 6, Elsevier, 2015, pp. 352–61, doi:10.1016/j.tibtech.2015.03.009.","short":"A. Angermayr, A. Gorchs, K. Hellingwerf, Trends in Biotechnology 33 (2015) 352–361.","ieee":"A. Angermayr, A. Gorchs, and K. Hellingwerf, “Metabolic engineering of cyanobacteria for the synthesis of commodity products,” Trends in Biotechnology, vol. 33, no. 6. Elsevier, pp. 352–361, 2015.","ama":"Angermayr A, Gorchs A, Hellingwerf K. Metabolic engineering of cyanobacteria for the synthesis of commodity products. Trends in Biotechnology. 2015;33(6):352-361. doi:10.1016/j.tibtech.2015.03.009","apa":"Angermayr, A., Gorchs, A., & Hellingwerf, K. (2015). Metabolic engineering of cyanobacteria for the synthesis of commodity products. Trends in Biotechnology. Elsevier. https://doi.org/10.1016/j.tibtech.2015.03.009"},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publist_id":"5585","author":[{"full_name":"Angermayr, Andreas","orcid":"0000-0001-8619-2223","last_name":"Angermayr","id":"4677C796-F248-11E8-B48F-1D18A9856A87","first_name":"Andreas"},{"last_name":"Gorchs","full_name":"Gorchs, Aleix","first_name":"Aleix"},{"first_name":"Klaas","last_name":"Hellingwerf","full_name":"Hellingwerf, Klaas"}],"title":"Metabolic engineering of cyanobacteria for the synthesis of commodity products","department":[{"_id":"ToBo"}],"_id":"1586","type":"journal_article","status":"public","year":"2015","publication_status":"published","day":"01","publication":"Trends in Biotechnology","language":[{"iso":"eng"}],"page":"352 - 361","volume":33,"doi":"10.1016/j.tibtech.2015.03.009","issue":"6","date_published":"2015-06-01T00:00:00Z","date_created":"2018-12-11T11:52:52Z","abstract":[{"text":"Through metabolic engineering cyanobacteria can be employed in biotechnology. Combining the capacity for oxygenic photosynthesis and carbon fixation with an engineered metabolic pathway allows carbon-based product formation from CO2, light, and water directly. Such cyanobacterial 'cell factories' are constructed to produce biofuels, bioplastics, and commodity chemicals. Efforts of metabolic engineers and synthetic biologists allow the modification of the intermediary metabolism at various branching points, expanding the product range. The new biosynthesis routes 'tap' the metabolism ever more efficiently, particularly through the engineering of driving forces and utilization of cofactors generated during the light reactions of photosynthesis, resulting in higher product titers. High rates of carbon rechanneling ultimately allow an almost-complete allocation of fixed carbon to product above biomass.","lang":"eng"}],"oa_version":"None","quality_controlled":"1","publisher":"Elsevier","scopus_import":1,"month":"06","intvolume":" 33"},{"file_date_updated":"2020-07-14T12:45:07Z","department":[{"_id":"ToBo"}],"date_updated":"2021-01-12T06:52:04Z","ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","pubrep_id":"467","status":"public","_id":"1623","license":"https://creativecommons.org/licenses/by/4.0/","volume":8,"issue":"1","publication_status":"published","language":[{"iso":"eng"}],"file":[{"file_name":"IST-2016-467-v1+1_s13068-015-0380-2.pdf","date_created":"2018-12-12T10:10:11Z","file_size":2914089,"date_updated":"2020-07-14T12:45:07Z","creator":"system","checksum":"172b0b6f4eb2e5c22b7cec1d57dc0107","file_id":"4796","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"scopus_import":1,"intvolume":" 8","month":"11","abstract":[{"text":"Background\r\nPhotosynthetic cyanobacteria are attractive for a range of biotechnological applications including biofuel production. However, due to slow growth, screening of mutant libraries using microtiter plates is not feasible.\r\nResults\r\nWe present a method for high-throughput, single-cell analysis and sorting of genetically engineered l-lactate-producing strains of Synechocystis sp. PCC6803. A microfluidic device is used to encapsulate single cells in picoliter droplets, assay the droplets for l-lactate production, and sort strains with high productivity. We demonstrate the separation of low- and high-producing reference strains, as well as enrichment of a more productive l-lactate-synthesizing population after UV-induced mutagenesis. The droplet platform also revealed population heterogeneity in photosynthetic growth and lactate production, as well as the presence of metabolically stalled cells.\r\nConclusions\r\nThe workflow will facilitate metabolic engineering and directed evolution studies and will be useful in studies of cyanobacteria biochemistry and physiology.\r\n","lang":"eng"}],"oa_version":"Published Version","publist_id":"5537","author":[{"first_name":"Petter","last_name":"Hammar","full_name":"Hammar, Petter"},{"first_name":"Andreas","id":"4677C796-F248-11E8-B48F-1D18A9856A87","last_name":"Angermayr","orcid":"0000-0001-8619-2223","full_name":"Angermayr, Andreas"},{"full_name":"Sjostrom, Staffan","last_name":"Sjostrom","first_name":"Staffan"},{"full_name":"Van Der Meer, Josefin","last_name":"Van Der Meer","first_name":"Josefin"},{"last_name":"Hellingwerf","full_name":"Hellingwerf, Klaas","first_name":"Klaas"},{"first_name":"Elton","full_name":"Hudson, Elton","last_name":"Hudson"},{"last_name":"Joensson","full_name":"Joensson, Hakaan","first_name":"Hakaan"}],"title":"Single-cell screening of photosynthetic growth and lactate production by cyanobacteria","citation":{"ista":"Hammar P, Angermayr A, Sjostrom S, Van Der Meer J, Hellingwerf K, Hudson E, Joensson H. 2015. Single-cell screening of photosynthetic growth and lactate production by cyanobacteria. Biotechnology for Biofuels. 8(1), 193.","chicago":"Hammar, Petter, Andreas Angermayr, Staffan Sjostrom, Josefin Van Der Meer, Klaas Hellingwerf, Elton Hudson, and Hakaan Joensson. “Single-Cell Screening of Photosynthetic Growth and Lactate Production by Cyanobacteria.” Biotechnology for Biofuels. BioMed Central, 2015. https://doi.org/10.1186/s13068-015-0380-2.","ama":"Hammar P, Angermayr A, Sjostrom S, et al. Single-cell screening of photosynthetic growth and lactate production by cyanobacteria. Biotechnology for Biofuels. 2015;8(1). doi:10.1186/s13068-015-0380-2","apa":"Hammar, P., Angermayr, A., Sjostrom, S., Van Der Meer, J., Hellingwerf, K., Hudson, E., & Joensson, H. (2015). Single-cell screening of photosynthetic growth and lactate production by cyanobacteria. Biotechnology for Biofuels. BioMed Central. https://doi.org/10.1186/s13068-015-0380-2","ieee":"P. Hammar et al., “Single-cell screening of photosynthetic growth and lactate production by cyanobacteria,” Biotechnology for Biofuels, vol. 8, no. 1. BioMed Central, 2015.","short":"P. Hammar, A. Angermayr, S. Sjostrom, J. Van Der Meer, K. Hellingwerf, E. Hudson, H. Joensson, Biotechnology for Biofuels 8 (2015).","mla":"Hammar, Petter, et al. “Single-Cell Screening of Photosynthetic Growth and Lactate Production by Cyanobacteria.” Biotechnology for Biofuels, vol. 8, no. 1, 193, BioMed Central, 2015, doi:10.1186/s13068-015-0380-2."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_number":"193","date_created":"2018-12-11T11:53:05Z","doi":"10.1186/s13068-015-0380-2","date_published":"2015-11-25T00:00:00Z","year":"2015","has_accepted_license":"1","publication":"Biotechnology for Biofuels","day":"25","oa":1,"publisher":"BioMed Central","quality_controlled":"1"},{"ec_funded":1,"volume":27,"language":[{"iso":"eng"}],"file":[{"checksum":"1683bb0f42ef892a5b3b71a050d65d25","file_id":"5277","access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2018-12-12T10:17:23Z","file_name":"IST-2016-493-v1+1_1-s2.0-S1369527415000594-main.pdf","creator":"system","date_updated":"2020-07-14T12:45:17Z","file_size":1047255}],"publication_status":"published","intvolume":" 27","month":"06","scopus_import":1,"oa_version":"Published Version","abstract":[{"text":"Combining antibiotics is a promising strategy for increasing treatment efficacy and for controlling resistance evolution. When drugs are combined, their effects on cells may be amplified or weakened, that is the drugs may show synergistic or antagonistic interactions. Recent work revealed the underlying mechanisms of such drug interactions by elucidating the drugs'; joint effects on cell physiology. Moreover, new treatment strategies that use drug combinations to exploit evolutionary tradeoffs were shown to affect the rate of resistance evolution in predictable ways. High throughput studies have further identified drug candidates based on their interactions with established antibiotics and general principles that enable the prediction of drug interactions were suggested. Overall, the conceptual and technical foundation for the rational design of potent drug combinations is rapidly developing.","lang":"eng"}],"department":[{"_id":"ToBo"}],"file_date_updated":"2020-07-14T12:45:17Z","ddc":["570"],"date_updated":"2021-01-12T06:53:21Z","pubrep_id":"493","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","_id":"1810","date_created":"2018-12-11T11:54:08Z","date_published":"2015-06-01T00:00:00Z","doi":"10.1016/j.mib.2015.05.008","page":"1 - 9","publication":"Current Opinion in Microbiology","day":"01","year":"2015","has_accepted_license":"1","oa":1,"publisher":"Elsevier","quality_controlled":"1","title":"Antimicrobial interactions: Mechanisms and implications for drug discovery and resistance evolution","author":[{"full_name":"Bollenbach, Mark Tobias","orcid":"0000-0003-4398-476X","last_name":"Bollenbach","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Mark Tobias"}],"publist_id":"5298","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Bollenbach, Mark Tobias. “Antimicrobial Interactions: Mechanisms and Implications for Drug Discovery and Resistance Evolution.” Current Opinion in Microbiology, vol. 27, Elsevier, 2015, pp. 1–9, doi:10.1016/j.mib.2015.05.008.","short":"M.T. Bollenbach, Current Opinion in Microbiology 27 (2015) 1–9.","ieee":"M. T. Bollenbach, “Antimicrobial interactions: Mechanisms and implications for drug discovery and resistance evolution,” Current Opinion in Microbiology, vol. 27. Elsevier, pp. 1–9, 2015.","apa":"Bollenbach, M. T. (2015). Antimicrobial interactions: Mechanisms and implications for drug discovery and resistance evolution. Current Opinion in Microbiology. Elsevier. https://doi.org/10.1016/j.mib.2015.05.008","ama":"Bollenbach MT. Antimicrobial interactions: Mechanisms and implications for drug discovery and resistance evolution. Current Opinion in Microbiology. 2015;27:1-9. doi:10.1016/j.mib.2015.05.008","chicago":"Bollenbach, Mark Tobias. “Antimicrobial Interactions: Mechanisms and Implications for Drug Discovery and Resistance Evolution.” Current Opinion in Microbiology. Elsevier, 2015. https://doi.org/10.1016/j.mib.2015.05.008.","ista":"Bollenbach MT. 2015. Antimicrobial interactions: Mechanisms and implications for drug discovery and resistance evolution. Current Opinion in Microbiology. 27, 1–9."},"project":[{"_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Revealing the mechanisms underlying drug interactions","grant_number":"P27201-B22"},{"_id":"25E83C2C-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"303507","name":"Optimality principles in responses to antibiotics"},{"grant_number":"RGP0042/2013","name":"Revealing the fundamental limits of cell growth","_id":"25EB3A80-B435-11E9-9278-68D0E5697425"}]}]