Living Yeast Sense-Respond Therapeutic Communities Engineered with Synthetic Biology

Project Summary The objective of this proposal is to broaden the capabilities of current synthetic biology tools by specifically focusing on yeast as biosensors, therapeutics, and as sense-and-respond communities. Living cells are positioned to be one of the next transformative technologies for therapeutic treatment. Rather than giving a purified small molecule or a purified protein as the drug, the living cell, in this case yeast, can be applied in situ at the site of disease that will continuously produce the necessary therapeutic. There are many advantages to using living yeast, as opposed to bacteria or mammalian cells as the in situ therapeutic, as they are cheap, easily scalable, easy to store, and Saccharomyces cerevisiae arguably has the most powerful genetic and synthetic biology tools for cell engineering. This project involves several different arms working in tandem: we plan to develop yeast that can sense different bacterial infections in wounds, yeast that can secrete different antibiotics in wounds, and finally yeast that secrete specific antibiotics in response to the bacteria present in the wound. This research combines our expertise working with antibiotics and wound healing to become a more sophisticated method of disease treatment. Yeast that can sense bacterial infections and secrete different antibiotics ultimately can be broadly applied beyond wound healing. The sensing and therapeutic approaches developed here should be broadly enabling in the longer term for making yeast sense-respond communities for treating human disease beyond bacterial infections and antibiotics.