title: 'Deadman' and 'Passcode' microbial kill switches for bacterial containment.
abstract: 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.
authors.affiliation: Institute for Medical Engineering &Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Clement T Y
authors.identifier: http://orcid.org/0000-0001-7940-3459
authors.initials: CT
authors.lastname: Chan
authors.affiliation: Institute for Medical Engineering &Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Jeong Wook
authors.identifier: http://orcid.org/0000-0003-0705-0177
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Institute for Medical Engineering &Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: D Ewen
authors.initials: DE
authors.lastname: Cameron
authors.affiliation: Institute for Medical Engineering &Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Caleb J
authors.initials: CJ
authors.lastname: Bashor
authors.affiliation: Institute for Medical Engineering &Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Harvard-MIT Program in Health Sciences and Technology, Cambridge, Massachusetts, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Collins
mesh_terms: D001419:Bacteria / Q000235:genetics*; D001427:Bacterial Toxins / Q000235:genetics; D003264:Containment of Biohazards / Q000379:methods*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D015964:Gene Expression Regulation, Bacterial; D009154:Mutation; D030781:Organisms, Genetically Modified / Q000235:genetics*
chemical_list: D001427:Bacterial Toxins