'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...

Full description

Bibliographic Details
Main Authors: Bashor, Caleb, Collins, James J., Chan, Clement T. Y., Lee, Jeongwook, Cameron, Douglas
Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science
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