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The Issue

Life-threatening pathogenic infections cause thousands of deaths every week all around the world. The effective and efficient identification of the infectious pathogens would facilitate the clinical treatment of these diseases. Nevertheless, current methods for identifying pathogen have many drawbacks, such as long period for testing, high cost and lack of portable facilities. The clinical diagnosis of the infectious pathogens would benefit significantly from the specific and sensitive pathogen identification methods better than existing methods such as pathogen culture, immunoassays and polymerase chain reaction (PCR) testing.

We designed a novel pathogen sensing system with the principles of synthetic biology as well as mobile health. This system could increase the speed and portability of pathogen identification, decrease the cost for producing practical facilities, and enable specific identification of distinct infectious pathogens. The challenge is addressed by implementing the genetically modified S. cerevisiae (budding yeast) for testing signal molecules from pathogens, which is supposed to be effective, reliable, safe and cost-effective.

Idea of the project

The project introduces the use of genetically engineered cells in a pathogen identification system. This system uses S. cerevisiae (budding yeast) that have been engineered to sense the signal molecules from pathogens or report the identification of pathogens, referred as sensing module and reporting module, respectively. By mating the sensing module and reporting module, two differently engineered yeasts, the signals from pathogens are sensed and reported by change in the color of the yeast colony. The N-Acyl Homoserine Lactone (AHL) is the signal for testing by the sensing module, which is the molecule for quorum sensing in Gram-negative bacteria with specificity for each different species of pathogens. Tetracycline-controlled transcriptional activation system (Tet-off system) is introduced to transmit signals from sensing module to reporting module. Considering the specificity and sensitivity of this pathogen identification sensor, this technology could prove useful for clinical test, medical diagnostics, water quality monitoring, and other potential applications.

Achievement

We introduced the genetically modified quorum sensing system from Gram-negative bacteria (LuxR-AHL controlled transcriptional activation system) to S. cerevisiae (budding yeast) by designing novel transcriptional activator and promoter, referred as LuxR-tVP16 and Plux-mCyc respectively.

We designed and completed the switching system by mating different reporting modules with the sensing module.

We constructed mathematical modeling to demonstrate the sensitivity and robustness of this system with combination of modified quorum sensing and tetracycline controlled transcriptional activation systems.

We introduced several safety mechanisms to this engineered biological testing machine.

We deposited several novel BioBricks to the Registry.

We improved the existing BioBricks.

We introduce the project and synthetic biology to society by making videos and other activities.