Collaborative Research: Engineering Genetically Augmented Polymers (GAPS)

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Synthetic biology is an emerging field that involves the design or re-design and manufacture of new biologically-inspired parts, modules, devices and systems. This has two major outputs. First, it tests scientific understanding of how life works and how it can be re-engineered at the most fundamental level. Second, it promises to put biological systems on a more modular and rational footing for subsequent engineering efforts. Foundational technologies need to be developed to make synthetic biology modular, scalable, and programmable. This project seeks to address this challenge by expanding biological space with Genetically Augmented PolymerS (GAPS) that will enable the design and manufacture of programmable networks and novel chemical function. Nucleobase amino acids (NAAs) will be synthesized and incorporated into natural polymers, proteins (pGAPS), and chemical polymers, polyvinyl nucleobases (cGAPS). In essence, by giving proteins and cells the ability to 'talk' with one another using the same code that DNA and RNA uses this proposal seeks to create a programmable ur-cell for biomedical engineering. This work will catalyze a new paradigm for engineering both chemical and biological systems. By melding the complexity and diversity of Biology with the predictability and high scalability of Chemistry, GAPS will pioneer new directions in synthetic biology. The addition of genetic information to proteins and cells will in general make biology more modular, scalable, and programmable. This should in turn enable the rational design and re-design of biological systems for compelling applications, such as controlling the wiring of interactomes and rationally modulating and programming cell function. For example, it should be possible to re-wire signaling pathways on a protein-by-protein basis, and to engineer tissues in a way that allows the precise, genetically-encoded placement of individual cells. Broader impact: In addition to creating a wholly new ur-cell platform for synthetic biology applications, the formation of a strong a UK-US team will have a considerable impact on the global leadership by these two countries in synthetic biology. The readily grasped goals of this project (programmable cells, replicating plastic) will provide opportunities for showing the public that synthetic biology is a field that yields translational technologies that can impact their own lives. Following up on the goals of the Sandpit, the international research team will establish and maintain a valuable network that provides for competitive, interdisciplinary, and globally-engaged research. This network will directly reach out to and involve students in synthetic biology (via iGEM, the Freshman Research Initiative, and "Current Protocols in Synthetic Biology"), and will begin to train a new generation of engineers who are comfortable operating between disciplines, labs, and continents. Moreover, the network will be of great use in engaging public interest and educating policy makers about the threats and benefits of synthetic biology, overall raising awareness of the ethical, legal and social impacts of synthetic biology.