Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies
Eukaryotic genes are regulated by multivalent transcription factor complexes. Through cooperative self-assembly, these complexes perform nonlinear regulatory operations involved in cellular decision-making and signal processing. In this study, we apply this design principle to synthetic networks, te...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/126317 |
| _version_ | 1811075321268535296 |
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| author | Bashor, Caleb J. Patel, Nikit Choubey, Sandeep Beyzavi, Ali Kondev, Jané Collins, James J. Khalil, Ahmad S. |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Bashor, Caleb J. Patel, Nikit Choubey, Sandeep Beyzavi, Ali Kondev, Jané Collins, James J. Khalil, Ahmad S. |
| author_sort | Bashor, Caleb J. |
| collection | MIT |
| description | Eukaryotic genes are regulated by multivalent transcription factor complexes. Through cooperative self-assembly, these complexes perform nonlinear regulatory operations involved in cellular decision-making and signal processing. In this study, we apply this design principle to synthetic networks, testing whether engineered cooperative assemblies can program nonlinear gene circuit behavior in yeast. Using a model-guided approach, we show that specifying the strength and number of assembly subunits enables predictive tuning between linear and nonlinear regulatory responses for single- and multi-input circuits. We demonstrate that assemblies can be adjusted to control circuit dynamics. We harness this capability to engineer circuits that perform dynamic filtering, enabling frequency-dependent decoding in cell populations. Programmable cooperative assembly provides a versatile way to tune the nonlinearity of network connections, markedly expanding the engineerable behaviors available to synthetic circuits. |
| first_indexed | 2024-09-23T10:04:12Z |
| format | Article |
| id | mit-1721.1/126317 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:04:12Z |
| publishDate | 2020 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1263172022-09-26T15:32:00Z Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies Bashor, Caleb J. Patel, Nikit Choubey, Sandeep Beyzavi, Ali Kondev, Jané Collins, James J. Khalil, Ahmad S. Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Synthetic Biology Center Eukaryotic genes are regulated by multivalent transcription factor complexes. Through cooperative self-assembly, these complexes perform nonlinear regulatory operations involved in cellular decision-making and signal processing. In this study, we apply this design principle to synthetic networks, testing whether engineered cooperative assemblies can program nonlinear gene circuit behavior in yeast. Using a model-guided approach, we show that specifying the strength and number of assembly subunits enables predictive tuning between linear and nonlinear regulatory responses for single- and multi-input circuits. We demonstrate that assemblies can be adjusted to control circuit dynamics. We harness this capability to engineer circuits that perform dynamic filtering, enabling frequency-dependent decoding in cell populations. Programmable cooperative assembly provides a versatile way to tune the nonlinearity of network connections, markedly expanding the engineerable behaviors available to synthetic circuits. DARPA (Grant W911NF-11-2-0056) 2020-07-22T18:25:40Z 2020-07-22T18:25:40Z 2019-04 2018-07 2020-03-05T16:28:12Z Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 https://hdl.handle.net/1721.1/126317 Bashor, Caleb J. et al. "Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies." Science 346, 6440 (May 2019): 593-597 © 2019 American Association for the Advancement of Science en http://dx.doi.org/10.1126/science.aau8287 Science Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Bashor, Caleb J. Patel, Nikit Choubey, Sandeep Beyzavi, Ali Kondev, Jané Collins, James J. Khalil, Ahmad S. Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies |
| title | Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies |
| title_full | Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies |
| title_fullStr | Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies |
| title_full_unstemmed | Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies |
| title_short | Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies |
| title_sort | complex signal processing in synthetic gene circuits using cooperative regulatory assemblies |
| url | https://hdl.handle.net/1721.1/126317 |
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