A model-driven approach to minimal cell engineering for medical therapy
Synthetic biology promises to enable researchers to design therapeutically and industrially valuable organisms. Achieving this promise requires new techniques for designing, synthesizing, and transplanting entire genomes. Here we propose to develop the first model-driven approach to synthetic biology, and use this approach to construct a bacterial chassis capable of synthesizing and delivering human lung therapies in situ. Specifically, we propose to develop a whole-cell model of the human lung pathogen M. pneumoniae, and use this model to design and construct a reduced, non-pathogenic chassis capable of delivering human lung therapies and/or vaccinations. This project will involve intimate integration of predictive modeling, genomic engineering, and systems and synthetic biology. Model predictions will provide direct input into genomic engineering, and the newly created strains will be characterized to refine the computational model. The project will produce the most accurate computational model of any organism to date, as well as produce the most reduced cell to date. In the future we anticipate this reduced chassis could be extended to synthesize and deliver small molecule and/or protein therapies to diseased lungs in situ.