Our Idea

To meet the foregoing challenge, a potable pathogen detector which is able to be reached anytime at hand is required. Our ¬detector is designed as the test paper, which emerges color change when pathogen is detected. The test paper possesses the advantage of low cost, quick output and easy storage. Moreover, it requires no expertise of medicine to use. Therefore, the detector in test paper form is a desired candidate to fit the idea of Mobile Health. However, what can be used as the main components to sense the pathogen as well as output the color change?

We are inspired by the idea of synthetic biology, in which living organisms are modified for various purpose and applications. Synthetic organisms are easy to manipulate and modify, which serves as the ideal candidate components for our detector. In our project, genetically modified S. cerevisiae (budding yeast) is utilized as the main component in the test paper. The yeast detects the signal of the bacteria and then reports it by expressing reporter genes. The yeast system is chosen generally based on four reasons: 1) Yeasts are small, fast proliferating organisms, whose genetic background are well understood. 2) Yeasts are eukaryotes, different from the target bacteria. It sets proper orthogonality between the detector and the target. 3) Being widely used in food and drinks manufacturing, yeasts are fundamentally friendlier to human health than other microorganisms. 4) Yeasts have the dramatic mechanism of mating. We take advantage of this mechanism to separate the sensor and reporter in our detector, increasing the flexibility and effectiveness of the system.

Then the next question is that, how will the yeast in our test paper detect the pathogen? Our first inspiration is to use the classic antigen-antibody reaction, in which specific antibodies are introduced in the detector to target and recognize the antigen of the pathogen. However, novel pathways are difficult to design in yeast to simultaneous include the input and output. Therefore, we asked the question: can we find and use pathways functioning in nature which detects specific bacteria populations? Qurom sensing, a conserved mechanism in bacteria to sense the population around, is detected and then used to suggest the appearance of the pathogen. In gram-negative bacteria, a small molecular in qurom sensing, called N-Acyl Homoserine Lactone (AHL), is release by the bacteria and convey the communicating message among the entire group. By using AHL, direct contact of pathogen and yeasts are avoided, reduce the possibility of contamination. Moreover, each species has its own specific AHL molecular, underling the specificity of the detector. Therefore, AHL is a potential candidate to identify the appearance as well as the size of a specific pathogen population. If the AHL sensing system of one pathogen is introduced in the yeast, then the yeast will work as the detector and sense the pathogen. Downstream reporter gene is expressed and it changes the color of the test paper.

Additionally, one unique feature of yeast against other microorganisms is that is has “gender”. Haploid yeasts with a type and α type can mate with each other to form a diploid. We use this feature of yeast to revise our detector system. Yeast in a type is utilized as the sensor, while Yeast in α type is in charge of the reporter. The sensor specificity target to interested pathogen and its AHL, while α type yeasts with different reporter colors is selected as the output. There are at least four main advantage of this: 1) the whole system is divided into two subparts, reducing the difficulty and time to build each part. 2) The flexibility of the system is increased. Different combination of sensors and reporter is accessible, making the system used as a potable toolbox and increasing the number of applicable detectors. 3) During the two-step process, the signal is amplified and easier to be detected. 4) New subparts are convenient to be added to the system, as it needs exclusively modification for only one part.

To summarize our idea, a potable detector in test paper form is designed with genetically modified yeasts. The sensor yeasts are able to sense the AHL signal of the pathogen and then the reporter yeasts reveal the signal with color change. We believe the system is an ideal model to fit the design of Mobile Health, making a potable and effective pathogen detector.