Mitigation of ribosome competition through distributed sRNA feedback (extended version)
This paper is an extended version of a paper of the same title accepted to Proceedings of the 55th IEEE Conference on Decision and Control (2016).
| Main Authors: | , |
|---|---|
| Format: | Technical Report |
| Language: | en_US |
| Published: |
2016
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/1721.1/104383 |
| _version_ | 1811089634222931968 |
|---|---|
| author | Qian, Yili Del Vecchio, Domitilla |
| author_facet | Qian, Yili Del Vecchio, Domitilla |
| author_sort | Qian, Yili |
| collection | MIT |
| description | This paper is an extended version of a paper of the same title accepted to Proceedings of the 55th IEEE Conference on Decision and Control (2016). |
| first_indexed | 2024-09-23T14:22:19Z |
| format | Technical Report |
| id | mit-1721.1/104383 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:22:19Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | mit-1721.1/1043832019-04-12T16:13:11Z Mitigation of ribosome competition through distributed sRNA feedback (extended version) Qian, Yili Del Vecchio, Domitilla Gene network Disturbance decoupling Distributed control small RNA Resource competition This paper is an extended version of a paper of the same title accepted to Proceedings of the 55th IEEE Conference on Decision and Control (2016). A current challenge in the robust engineering of synthetic gene networks is context dependence, the unintended interactions among genes and host factors. Ribosome competition is a specific form of context dependence, where all genes in the network compete for a limited pool of translational resources available for gene expression. Recently, theoretical and experimental studies have shown that ribosome competition creates a hidden layer of interactions among genes, which largely hinders our ability to predict design outcomes. In this work, we establish a control theoretic framework, where these hidden interactions become disturbance signals. We then propose a distributed feedback mechanism to achieve disturbance decoupling in the network. The feedback loop at each node consists of the protein product transcriptionally activating a small RNA (sRNA), which forms a translationally inactive complex with mRNA rapidly. We illustrate that with this feedback mechanism, protein production at each node is only dependent on its own transcription factor inputs, and almost independent of hidden interactions arising from ribosome competition. AFOSR grant FA9550-12-1-0129 and ONR grant N000141310074 2016-09-23T17:04:19Z 2016-09-23T17:04:19Z 2016-09-23 Technical Report http://hdl.handle.net/1721.1/104383 en_US Attribution-NonCommercial 3.0 United States http://creativecommons.org/licenses/by-nc/3.0/us/ application/pdf |
| spellingShingle | Gene network Disturbance decoupling Distributed control small RNA Resource competition Qian, Yili Del Vecchio, Domitilla Mitigation of ribosome competition through distributed sRNA feedback (extended version) |
| title | Mitigation of ribosome competition through distributed sRNA feedback (extended version) |
| title_full | Mitigation of ribosome competition through distributed sRNA feedback (extended version) |
| title_fullStr | Mitigation of ribosome competition through distributed sRNA feedback (extended version) |
| title_full_unstemmed | Mitigation of ribosome competition through distributed sRNA feedback (extended version) |
| title_short | Mitigation of ribosome competition through distributed sRNA feedback (extended version) |
| title_sort | mitigation of ribosome competition through distributed srna feedback extended version |
| topic | Gene network Disturbance decoupling Distributed control small RNA Resource competition |
| url | http://hdl.handle.net/1721.1/104383 |
| work_keys_str_mv | AT qianyili mitigationofribosomecompetitionthroughdistributedsrnafeedbackextendedversion AT delvecchiodomitilla mitigationofribosomecompetitionthroughdistributedsrnafeedbackextendedversion |