A quasi-integral controller for adaptation of genetic modules to variable ribosome demand
The behavior of genetic circuits is often poorly predictable. A gene’s expression level is not only determined by the intended regulators, but also affected by changes in ribosome availability imparted by expression of other genes. Here we design a quasi-integral biomolecular feedback controller tha...
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| Format: | Article |
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Nature Publishing Group
2019
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| Online Access: | http://hdl.handle.net/1721.1/121039 https://orcid.org/0000-0003-2435-480X https://orcid.org/0000-0002-1097-0401 https://orcid.org/0000-0001-6472-8576 |
| _version_ | 1811070590535073792 |
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| author | Huang, Hsin-Ho Qian, Yili Del Vecchio, Domitilla |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Huang, Hsin-Ho Qian, Yili Del Vecchio, Domitilla |
| author_sort | Huang, Hsin-Ho |
| collection | MIT |
| description | The behavior of genetic circuits is often poorly predictable. A gene’s expression level is not only determined by the intended regulators, but also affected by changes in ribosome availability imparted by expression of other genes. Here we design a quasi-integral biomolecular feedback controller that enables the expression level of any gene of interest (GOI) to adapt to changes in available ribosomes. The feedback is implemented through a synthetic small RNA (sRNA) that silences the GOI’s mRNA, and uses orthogonal extracytoplasmic function (ECF) sigma factor to sense the GOI’s translation and to actuate sRNA transcription. Without the controller, the expression level of the GOI is reduced by 50% when a resource competitor is activated. With the controller, by contrast, gene expression level is practically unaffected by the competitor. This feedback controller allows adaptation of genetic modules to variable ribosome demand and thus aids modular construction of complicated circuits. |
| first_indexed | 2024-09-23T08:38:27Z |
| format | Article |
| id | mit-1721.1/121039 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T08:38:27Z |
| publishDate | 2019 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1210392022-09-23T13:29:16Z A quasi-integral controller for adaptation of genetic modules to variable ribosome demand Huang, Hsin-Ho Qian, Yili Del Vecchio, Domitilla Massachusetts Institute of Technology. Department of Mechanical Engineering Huang, Hsin-Ho Qian, Yili Del Vecchio, Domitilla The behavior of genetic circuits is often poorly predictable. A gene’s expression level is not only determined by the intended regulators, but also affected by changes in ribosome availability imparted by expression of other genes. Here we design a quasi-integral biomolecular feedback controller that enables the expression level of any gene of interest (GOI) to adapt to changes in available ribosomes. The feedback is implemented through a synthetic small RNA (sRNA) that silences the GOI’s mRNA, and uses orthogonal extracytoplasmic function (ECF) sigma factor to sense the GOI’s translation and to actuate sRNA transcription. Without the controller, the expression level of the GOI is reduced by 50% when a resource competitor is activated. With the controller, by contrast, gene expression level is practically unaffected by the competitor. This feedback controller allows adaptation of genetic modules to variable ribosome demand and thus aids modular construction of complicated circuits. 2019-03-19T13:48:37Z 2019-03-19T13:48:37Z 2018-12 2018-06 2019-03-01T14:00:58Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/121039 Huang, Hsin-Ho, Yili Qian, and Domitilla Del Vecchio. “A Quasi-Integral Controller for Adaptation of Genetic Modules to Variable Ribosome Demand.” Nature Communications 9, no. 1 (December 2018). https://orcid.org/0000-0003-2435-480X https://orcid.org/0000-0002-1097-0401 https://orcid.org/0000-0001-6472-8576 http://dx.doi.org/10.1038/s41467-018-07899-z Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Huang, Hsin-Ho Qian, Yili Del Vecchio, Domitilla A quasi-integral controller for adaptation of genetic modules to variable ribosome demand |
| title | A quasi-integral controller for adaptation of genetic modules to variable ribosome demand |
| title_full | A quasi-integral controller for adaptation of genetic modules to variable ribosome demand |
| title_fullStr | A quasi-integral controller for adaptation of genetic modules to variable ribosome demand |
| title_full_unstemmed | A quasi-integral controller for adaptation of genetic modules to variable ribosome demand |
| title_short | A quasi-integral controller for adaptation of genetic modules to variable ribosome demand |
| title_sort | quasi integral controller for adaptation of genetic modules to variable ribosome demand |
| url | http://hdl.handle.net/1721.1/121039 https://orcid.org/0000-0003-2435-480X https://orcid.org/0000-0002-1097-0401 https://orcid.org/0000-0001-6472-8576 |
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