Engineering modular intracellular protein sensor-actuator devices
Understanding and reshaping cellular behaviors with synthetic gene networks requires the ability to sense and respond to changes in the intracellular environment. Intracellular proteins are involved in almost all cellular processes, and thus can provide important information about changes in cellula...
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/117730 https://orcid.org/0000-0001-7734-9153 https://orcid.org/0000-0002-0302-6834 https://orcid.org/0000-0002-6351-7256 https://orcid.org/0000-0003-0396-2443 |
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| author | Monel, Blandine Beal, Jacob Clayton, Kiera L Wroblewska, Liliana McKeon, AnneMarie Walker, Bruce D. Siciliano, Velia DiAndreth, Breanna Huh, Jin Hang Weiss, Ron |
| author2 | Institute for Medical Engineering and Science |
| author_facet | Institute for Medical Engineering and Science Monel, Blandine Beal, Jacob Clayton, Kiera L Wroblewska, Liliana McKeon, AnneMarie Walker, Bruce D. Siciliano, Velia DiAndreth, Breanna Huh, Jin Hang Weiss, Ron |
| author_sort | Monel, Blandine |
| collection | MIT |
| description | Understanding and reshaping cellular behaviors with synthetic gene networks requires the ability to sense and respond to changes in the intracellular environment. Intracellular proteins are involved in almost all cellular processes, and thus can provide important information about changes in cellular conditions such as infections, mutations, or disease states. Here we report the design of a modular platform for intrabody-based protein sensing-Actuation devices with transcriptional output triggered by detection of intracellular proteins in mammalian cells. We demonstrate reporter activation response (fluorescence, apoptotic gene) to proteins involved in hepatitis C virus (HCV) infection, human immunodeficiency virus (HIV) infection, and Huntington's disease, and show sensor-based interference with HIV-1 downregulation of HLA-I in infected T cells. Our method provides a means to link varying cellular conditions with robust control of cellular behavior for scientific and therapeutic applications. |
| first_indexed | 2024-09-23T16:07:07Z |
| format | Article |
| id | mit-1721.1/117730 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:07:07Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1177302022-10-02T06:27:34Z Engineering modular intracellular protein sensor-actuator devices Monel, Blandine Beal, Jacob Clayton, Kiera L Wroblewska, Liliana McKeon, AnneMarie Walker, Bruce D. Siciliano, Velia DiAndreth, Breanna Huh, Jin Hang Weiss, Ron Institute for Medical Engineering and Science Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Synthetic Biology Center Siciliano, Velia DiAndreth, Breanna Huh, Jin Hang Weiss, Ron Understanding and reshaping cellular behaviors with synthetic gene networks requires the ability to sense and respond to changes in the intracellular environment. Intracellular proteins are involved in almost all cellular processes, and thus can provide important information about changes in cellular conditions such as infections, mutations, or disease states. Here we report the design of a modular platform for intrabody-based protein sensing-Actuation devices with transcriptional output triggered by detection of intracellular proteins in mammalian cells. We demonstrate reporter activation response (fluorescence, apoptotic gene) to proteins involved in hepatitis C virus (HCV) infection, human immunodeficiency virus (HIV) infection, and Huntington's disease, and show sensor-based interference with HIV-1 downregulation of HLA-I in infected T cells. Our method provides a means to link varying cellular conditions with robust control of cellular behavior for scientific and therapeutic applications. United States. Defense Advanced Research Projects Agency (Grant W911NF-11-2-0054) National Institutes of Health (U.S.) (Grant P50 GM098792) 2018-09-12T19:37:44Z 2018-09-12T19:37:44Z 2018-05 2018-02 2018-09-12T14:26:12Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/117730 Siciliano, Velia et al. “Engineering Modular Intracellular Protein Sensor-Actuator Devices.” Nature Communications 9, 1 (May 2018): 1881 © 2018 The Author(s) https://orcid.org/0000-0001-7734-9153 https://orcid.org/0000-0002-0302-6834 https://orcid.org/0000-0002-6351-7256 https://orcid.org/0000-0003-0396-2443 http://dx.doi.org/10.1038/s41467-018-03984-5 Nature Communications Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Monel, Blandine Beal, Jacob Clayton, Kiera L Wroblewska, Liliana McKeon, AnneMarie Walker, Bruce D. Siciliano, Velia DiAndreth, Breanna Huh, Jin Hang Weiss, Ron Engineering modular intracellular protein sensor-actuator devices |
| title | Engineering modular intracellular protein sensor-actuator devices |
| title_full | Engineering modular intracellular protein sensor-actuator devices |
| title_fullStr | Engineering modular intracellular protein sensor-actuator devices |
| title_full_unstemmed | Engineering modular intracellular protein sensor-actuator devices |
| title_short | Engineering modular intracellular protein sensor-actuator devices |
| title_sort | engineering modular intracellular protein sensor actuator devices |
| url | http://hdl.handle.net/1721.1/117730 https://orcid.org/0000-0001-7734-9153 https://orcid.org/0000-0002-0302-6834 https://orcid.org/0000-0002-6351-7256 https://orcid.org/0000-0003-0396-2443 |
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