This app is part of the Colourectal project from the iGEM Wageningen team. The app acts as a demonstration tool for the project.
The Colourectal project explained:
Colorectal cancer is the second most deadly cancer worldwide. Currently employed screening methods suffer from low detection rates and result in frequent false positives, leading to missed diagnoses or unnecessary, invasive follow-up treatments. We therefore created an easy-to-use living diagnostic tool called Colourectal. The probiotic strain Escherichia coli Nissle 1917 was engineered to bind to tumour cells, detect two distinct cancer biomarkers, and secrete a coloured protein in the stool. Lactate serves as the first biomarker. We modelled and constructed a threshold-based circuit that uses this biomarker as an inducer resulting in expression of a signal protein at significantly elevated lactate levels. The second biomarker, matrix metalloproteinase 9, activates the colour of our signal protein. Only when both biomarkers are present will our signal protein be observed in the stool. Additionally, we have implemented biosafety circuits to limit viability of E. coli Nissle 1917 to the colon, by creating a dependence on temperature and mucin. A third layer of biosafety ensures removal of the bacterium when desired, turning Colourectal into a self-test. Further, we have modelled persistence of our living diagnostic in the gut and used this to determine an optimal administration strategy. The detection of two different early cancer biomarkers and the three layers of biosafety, potentially make Colourectal a safe and sensitive alternative to current screening methods.
The Colourectal project explained:
Colorectal cancer is the second most deadly cancer worldwide. Currently employed screening methods suffer from low detection rates and result in frequent false positives, leading to missed diagnoses or unnecessary, invasive follow-up treatments. We therefore created an easy-to-use living diagnostic tool called Colourectal. The probiotic strain Escherichia coli Nissle 1917 was engineered to bind to tumour cells, detect two distinct cancer biomarkers, and secrete a coloured protein in the stool. Lactate serves as the first biomarker. We modelled and constructed a threshold-based circuit that uses this biomarker as an inducer resulting in expression of a signal protein at significantly elevated lactate levels. The second biomarker, matrix metalloproteinase 9, activates the colour of our signal protein. Only when both biomarkers are present will our signal protein be observed in the stool. Additionally, we have implemented biosafety circuits to limit viability of E. coli Nissle 1917 to the colon, by creating a dependence on temperature and mucin. A third layer of biosafety ensures removal of the bacterium when desired, turning Colourectal into a self-test. Further, we have modelled persistence of our living diagnostic in the gut and used this to determine an optimal administration strategy. The detection of two different early cancer biomarkers and the three layers of biosafety, potentially make Colourectal a safe and sensitive alternative to current screening methods.
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