'Deadman' and 'Passcode' microbial kill switches for bacterial containment
Biocontainment systems that couple environmental sensing with circuit-based control of cell viability could be used to prevent escape of genetically modified microbes into the environment. Here we present two engineered safeguard systems known as the 'Deadman' and 'Passcode' kill...
Main Authors: | , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | en_US |
Published: |
Nature Publishing Group
2017
|
Online Access: | http://hdl.handle.net/1721.1/108106 https://orcid.org/0000-0002-5560-8246 https://orcid.org/0000-0003-0705-0177 |
_version_ | 1826216058978041856 |
---|---|
author | Bashor, Caleb Collins, James J. Chan, Clement T. Y. Lee, Jeongwook Cameron, Douglas |
author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Bashor, Caleb Collins, James J. Chan, Clement T. Y. Lee, Jeongwook Cameron, Douglas |
author_sort | Bashor, Caleb |
collection | MIT |
description | Biocontainment systems that couple environmental sensing with circuit-based control of cell viability could be used to prevent escape of genetically modified microbes into the environment. Here we present two engineered safeguard systems known as the 'Deadman' and 'Passcode' kill switches. The Deadman kill switch uses unbalanced reciprocal transcriptional repression to couple a specific input signal with cell survival. The Passcode kill switch uses a similar two-layered transcription design and incorporates hybrid LacI-GalR family transcription factors to provide diverse and complex environmental inputs to control circuit function. These synthetic gene circuits efficiently kill Escherichia coli and can be readily reprogrammed to change their environmental inputs, regulatory architecture and killing mechanism. |
first_indexed | 2024-09-23T16:41:38Z |
format | Article |
id | mit-1721.1/108106 |
institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T16:41:38Z |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | dspace |
spelling | mit-1721.1/1081062022-10-03T07:39:48Z 'Deadman' and 'Passcode' microbial kill switches for bacterial containment Bashor, Caleb Collins, James J. Chan, Clement T. Y. Lee, Jeongwook Cameron, Douglas Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Synthetic Biology Center Harvard University--MIT Division of Health Sciences and Technology Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biological Engineering Bashor, Caleb Collins, James J. Chan, Clement T. Y. Lee, Jeongwook Cameron, Douglas Biocontainment systems that couple environmental sensing with circuit-based control of cell viability could be used to prevent escape of genetically modified microbes into the environment. Here we present two engineered safeguard systems known as the 'Deadman' and 'Passcode' kill switches. The Deadman kill switch uses unbalanced reciprocal transcriptional repression to couple a specific input signal with cell survival. The Passcode kill switch uses a similar two-layered transcription design and incorporates hybrid LacI-GalR family transcription factors to provide diverse and complex environmental inputs to control circuit function. These synthetic gene circuits efficiently kill Escherichia coli and can be readily reprogrammed to change their environmental inputs, regulatory architecture and killing mechanism. United States. Defense Threat Reduction Agency (Grant HDTRA1-14-1-0006) Howard Hughes Medical Institute United States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant N000141110725) United States. Air Force Office of Scientific Research (Grant FA9550-14-1-0060) 2017-04-13T14:56:23Z 2017-04-13T14:56:23Z 2015-12 2015-03 Article http://purl.org/eprint/type/JournalArticle 1552-4450 1552-4469 http://hdl.handle.net/1721.1/108106 Chan, Clement T Y, Jeong Wook Lee, D Ewen Cameron, Caleb J Bashor, and James J Collins. “‘Deadman’ and ‘Passcode’ Microbial Kill Switches for Bacterial Containment.” Nature Chemical Biology 12, no. 2 (December 7, 2015): 82–86. https://orcid.org/0000-0002-5560-8246 https://orcid.org/0000-0003-0705-0177 en_US http://dx.doi.org/10.1038/nchembio.1979 Nature Chemical Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
spellingShingle | Bashor, Caleb Collins, James J. Chan, Clement T. Y. Lee, Jeongwook Cameron, Douglas 'Deadman' and 'Passcode' microbial kill switches for bacterial containment |
title | 'Deadman' and 'Passcode' microbial kill switches for bacterial containment |
title_full | 'Deadman' and 'Passcode' microbial kill switches for bacterial containment |
title_fullStr | 'Deadman' and 'Passcode' microbial kill switches for bacterial containment |
title_full_unstemmed | 'Deadman' and 'Passcode' microbial kill switches for bacterial containment |
title_short | 'Deadman' and 'Passcode' microbial kill switches for bacterial containment |
title_sort | deadman and passcode microbial kill switches for bacterial containment |
url | http://hdl.handle.net/1721.1/108106 https://orcid.org/0000-0002-5560-8246 https://orcid.org/0000-0003-0705-0177 |
work_keys_str_mv | AT bashorcaleb deadmanandpasscodemicrobialkillswitchesforbacterialcontainment AT collinsjamesj deadmanandpasscodemicrobialkillswitchesforbacterialcontainment AT chanclementty deadmanandpasscodemicrobialkillswitchesforbacterialcontainment AT leejeongwook deadmanandpasscodemicrobialkillswitchesforbacterialcontainment AT camerondouglas deadmanandpasscodemicrobialkillswitchesforbacterialcontainment |