Arsenic water sensor (ArsR + CRISPRi)

Detects arsenite in drinking water. The validated ArsR/Pars sensing module gates an sgRNA that, with dCas9, represses a constitutive sfGFP reporter (CRISPRi inverter). Built in safe E. coli K-12.

Environmental contaminantBSL-1 chassistemplatearsenicheavy-metalwaterenvironmentalCRISPRifield
Input
Arsenite As(III)
Environmental contaminant
Sense
CRISPRi-repression
dCas9 (S. pyogenes, catalytically dead)
Chassis
E. coli K-12 (MG1655)
BSL-1
Output
sfGFP
fluorescent

What it detects

Analyte
Arsenite As(III) — ArsR sensing module responds around the WHO limit of 10 µg/L (~0.13 µM) up to tens of µg/L
Category
Environmental contaminant
Signal
Inorganic arsenic in drinking/ground water

Genetic circuit

⤢ click to enlarge

Genetic construct (SBOL)

The DNA construct as transcription units, drawn with SBOL Visual part glyphs.

⤢ click to enlarge

CRISPR sensing mechanism

Strategy
CRISPRi-repression · NOT logic
Cas protein
dCas9 (S. pyogenes, catalytically dead)
Analyte sensor
Arsenite binds the ArsR repressor, releasing it from the Pars operator and de-repressing the Pars promoter.
Signal flow
As(III) -> ArsR releases Pars -> Pars transcribes an sgRNA -> sgRNA + dCas9 bind and repress the constitutive sfGFP cassette (CRISPRi) -> green fluorescence falls as arsenic rises (NOT gate). A second CRISPRi inverter stage flips this to signal-ON if a turn-on readout is preferred.

Safe chassis

E. coli K-12 (MG1655)Escherichia coli

The non-pathogenic laboratory workhorse. K-12 strains have lost the ability to colonize the human gut and are the reference BSL-1 host for genetic engineering, with the deepest tooling of any bacterial chassis.

BSL-1

Genetic parts

PartRoleSource / id
ArsR repressor
Arsenite-responsive transcriptional repressor.
regulatorBBa_J33201 (arsR/Pars module)
Pars promoter/operator
De-repressed when ArsR binds arsenite.
promoterBBa_J33201
Anti-sfGFP sgRNA
Transcribed from Pars; spacer targets the reporter promoter for CRISPRi knockdown.
sgRNAdesigned to target the sfGFP promoter region
sgRNA scaffold (SpCas9)
GTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGC
sgRNAStandard S. pyogenes sgRNA scaffold (Qi et al. 2013)
dCas9
Constitutively expressed; catalytically dead, blocks transcription when guided.
dCas9Addgene dCas9 (D10A/H840A); Qi et al. 2013, Cell
J23119 constitutive promoter
Drives the sfGFP reporter (target of CRISPRi).
TTGACAGCTAGCTCAGTCCTAGGTATAATGCTAGC
promoterBBa_J23119
B0034 RBS
AAAGAGGAGAAA
rbsBBa_B0034
sfGFP
Reporter whose level reports arsenic.
reporterPedelacq et al. 2006

Output & readout

Type
fluorescent
Reporter
sfGFP
Readout
Green fluorescence (plate reader or field fluorimeter)
Positive result
Fluorescence change proportional to arsenic concentration.

Performance

Limit of detection
ArsR sensing module is validated near 10 µg/L (WHO arsenic limit).
Dynamic range
~10-100 µg/L for the native ArsR module
Response time
~120 min
Device validated
No — design template (parts validated individually)

The ArsR/Pars sensing module and CRISPRi are each individually validated in the literature; this specific integrated CRISPRi device is a design template and has not been validated end to end here.

Safety

Biosafety level
BSL-1 (non-pathogenic chassis)
GRAS chassis
No
Biocontainment
Lab/contained use; auxotrophic kill-switch recommended before any field deployment.
Field-deployable
Yes (with containment)

E. coli K-12 is a non-pathogenic BSL-1 host.

Build & run

#StageStep
1designDesign the anti-reporter sgRNA
Pick a 20-nt spacer targeting the sfGFP promoter/5'UTR with a PAM; check off-targets against the host genome.
2assemblyAssemble the two transcription units
TU1: Pars -> sgRNA. TU2: constitutive dCas9 + J23119-sfGFP reporter. Clone into a SEVA vector.
3transformationTransform E. coli K-12
Transform and select; verify dCas9 and reporter expression in the absence of arsenic.
4inductionExpose to sample
Incubate cells with the water sample (and an arsenic standard curve).
5readoutMeasure fluorescence
Read sfGFP; interpolate arsenic concentration from the standard curve.

Source & parts

Design
Design template combining a validated ArsR/Pars arsenic-sensing module with a dCas9 CRISPRi reporter circuit
Parts validated in
  • Stocker et al. 2003, Environ. Sci. Technol. (ArsR-based arsenic biosensor)
  • iGEM Edinburgh 2006 arsenic biosensor (BBa_J33201)
  • Qi et al. 2013, Cell (CRISPRi / dCas9)
License
Parts per their original sources; design template CC BY 4.0