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                <p>Inflammatory bowel disease (IBD) results in chronic inflammation of the intestines. Current diagnostic methods are invasive and rely on biomarkers that are not sufficiently disease-specific. We have engineered <i>E. coli</i> to detect several disease-specific biomarkers, memorize this event, and allow specific readout of the memory state. While the sensor cells travel through the gut, simultaneously occurring signals are memorized by activating an AND gate which triggers a recombination-based unidirectional switch and commits the observation to memory. After isolation from the patient’s faeces, the memory can be read out through the expression of a fluorescent protein induced by the addition of the candidate biomarker. Thus a single fluorescent protein can differentiate between many different candidate markers. A community of sensor cells can be utilized at the same time, enabling a high degree of multiplexing. Pavlov’s Coli is a non-invasive diagnostic tool for a large selection of specific biomarkers associated with IBD.
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                <p>Inflammatory bowel disease (IBD) results in chronic inflammation of the intestines. Current diagnostic methods are invasive and rely on biomarkers that are not sufficiently disease-specific. We have engineered <i>E. coli</i> to detect several disease-specific biomarkers, memorize this event, and allow specific readout of the memory state. While the sensor cells travel through the gut, simultaneously occurring signals are memorized by activating an AND gate which triggers a recombination-based unidirectional switch and commits the observation to memory. After isolation from the patient’s faeces, the memory can be read out through the expression of a fluorescent protein induced by the addition of the candidate biomarker. Thus a single fluorescent protein can differentiate between many different candidate markers. A community of sensor cells can be utilized at the same time, enabling a high degree of multiplexing. Pavlov’s Coli is a non-invasive diagnostic tool for a large selection of specific biomarkers associated with IBD.
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Revision as of 21:56, 15 October 2016

PAVLOV'S COLI

ABSTRACT

Inflammatory bowel disease (IBD) results in chronic inflammation of the intestines. Current diagnostic methods are invasive and rely on biomarkers that are not sufficiently disease-specific. We have engineered E. coli to detect several disease-specific biomarkers, memorize this event, and allow specific readout of the memory state. While the sensor cells travel through the gut, simultaneously occurring signals are memorized by activating an AND gate which triggers a recombination-based unidirectional switch and commits the observation to memory. After isolation from the patient’s faeces, the memory can be read out through the expression of a fluorescent protein induced by the addition of the candidate biomarker. Thus a single fluorescent protein can differentiate between many different candidate markers. A community of sensor cells can be utilized at the same time, enabling a high degree of multiplexing. Pavlov’s Coli is a non-invasive diagnostic tool for a large selection of specific biomarkers associated with IBD.

CONTACT

REFERENCES

  • [1] Maciej Chichlowski and Laura P Hale. “Bacterial-mucosal interactions in inflammatory bowel disease: an alliance gone bad”. In: American Journal of Physiology-Gastrointestinal and Liver Physiology 295.6 (2008), G1139–G1149.
  • [2] Mike G Laukoetter, Porfirio Nava, and Asma Nusrat. “Role of the intestinal barrier in inflammatory bowel disease”. In: World Journal of Gastroenterology 14.3 (2008), p. 401.
  • [3] Eric J Archer, Andra B Robinson, and Gürol M Süel. “Engineered E. coli that detect and respond to gut inflammation through nitric oxide sensing”. In: ACS synthetic biology 1.10 (2012), pp. 451–457.
  • [4] Jessica Ann Thompson et al. “Manipulation of the quorum sensing signal AI-2 affects the antibiotic-treated gut microbiota”. In: Cell reports 10.11 (2015), pp. 1861–1871.
  • [5] Timothy D Minogue et al. “The autoregulatory role of EsaR, a quorum-sensing regulator in Pantoea stewartii ssp. stewartii: evidence for a repressor function”. In: Molecular microbiology 44.6 (2002), pp. 1625– 1635.
  • [6] Cynthia H Collins, Jared R Leadbetter, and Frances H Arnold. “Dual selection enhances the signaling specificity of a variant of the quorum-sensing transcriptional activator LuxR”. In: Nature biotechnology 24.6 (2006), pp. 708–712.
  • [7] Gilaad G Kaplan. “The global burden of IBD: from 2015 to 2025”. In: Nature Reviews Gastroenterology & Hepatology 12.12 (2015), pp. 720–727.

Thanks to the sponsors that supported our project: