(447h) Synthetic Cell-Based Devices for Diagnosis, Treatment and Discovery

The ability to engineer customized mammalian cellular functions would enable the construction of sophisticated cell-based therapeutics and transformative tools for fundamental biological research. Such capabilities could overcome persistent barriers to treatment in applications ranging from cancer immunotherapy to regenerative medicine. The emerging field of synthetic biology provides such an approach for building novel cellular functions from the bottom up, and the “toolbox” of biological parts that operate in mammalian cells is rapidly expanding. To date, however, we lack the ability to construct synthetic cell-based biosensors that detect and respond to exclusively extracellular cues. Because many species of biological relevance, including cytokines, chemokines, cell-surface antigens, and many pathogens are exclusively extracellular, engineering cell-based devices that interface robustly with host physiology will require sensors for extracellular species. Here, I will discuss our work developing novel synthetic biology tools that address this need, with a focus on engineering protein components that enable the construction of cell-based biosensors. I will also discuss our application of these technologies to probe interactions between cancer and the immune system, and to develop effective therapies that harness the immune system to control or eradicate cancer.