Project Summary

The motivation of our project is to create a new model for therapeutic treatment that would detect target cells among healthy cells in the intestine for the strictly controlled release of therapeutics. Our treatment could be applied to a variety of diseases local to the intestine, including colon cancer and inflammatory bowel disease. The impact of this would be profound, as patients would experience fewer side effects due to reduced damage to their healthy cells. Our probiotics will continuously produce a therapeutic for the respective disease. We plan on recognizing target cells by their overexpression of unique transmembrane proteins. This will allow our engineered probiotic to bind at sites of higher concentration of target cells since there are more binding locations than on normal cells. Then we will utilize quorum sensing, a concentration-based way of bacterial communication. Once the concentration of bacteria is high enough (above a specific threshold) to produce the necessary signal, the bacteria will respond by lysing and releasing the respective therapeutic only in these targeted areas. Our project builds on ideas from last year’s Princeton iGEM team by applying the "stick-and-secrete" technology to the treatment of diseases such as cancer or IBD.

Our Inspirations

Our project originally wanted to focus on IBD because of the severity that the condition brings combined with the limitations in modern treatment. Additionally, working in the intestines creates the perfect environment for the deployment of synthetically engineered therapeutic bacteria. However, as we began to put things into place, we realized we could expand the scope of our project by including colon cancer as a secondary model. In this way, our project became even more powerful through its capacity as a novel therapeutic delivery method for any intestinal disease.

Our Process

Our team began last semester as a seminar class where we were given a crash course in all things synthetic biology. Most of us learned everything new, from the ground up. For our midterms and final projects, we did thorough research given our knowledge of previous work to create a series of project proposals for potential iGEM projects we found inspiring. Together, we worked on critiquing and combining our ideas into the rough idea of a self-bursting probiotic therapy. From there, we doubled down on developing the BOOMcoli idea, creating the final plan that we took into the lab over the summer.

References

1. Riglar, D. T., Richmond, D. L., Potvin-Trottier, L., Verdegaal, A. A., Naydich, A. D., Bakshi, S., Leoncini, E., Lyon, L. G., Paulsson, J., & Silver, P. A. (2019). Bacterial variability in the mammalian gut captured by a single-cell synthetic oscillator. Nature Communications, 10, 4665. https://doi.org/10.1038/s41467-019-12638-z
2. Scott, S. R., Din, M. O., Bittihn, P., Xiong, L., Tsimring, L. S., & Hasty, J. (2017). A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis. Nature Microbiology, 2(8), 1–9. https://doi.org/10.1038/nmicrobiol.2017.83
3. Stephens, K., & Bentley, W. E. (2020). Synthetic Biology for Manipulating Quorum Sensing in Microbial Consortia. Trends in Microbiology, 28(8), 633–643. https://doi.org/10.1016/j.tim.2020.03.009
4. Wassenaar, T. M. (2016). Insights from 100 Years of Research with Probiotic E. Coli. European Journal of Microbiology & Immunology, 6(3), 147–161. https://doi.org/10.1556/1886.2016.00029