ERASynBio: BioMolecular Origami

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This project, funded by the Systems and Synthetic Biology Program in MCB and the Biotechnology, Biochemical and Biomass Engineering Program in CBET, is part of a larger ERASynBio funded collaborative. The team of investigators will develop the rules that govern the design of complex nanometer scale structures made from nucleic acids and polypeptides, and use those rules to create new biological molecules that have never been seen before in nature. They will also develop the tools that will enable the assembly of these new materials that could potentially be used to control many aspects of cell function, or create new materials that could be used as sensors or in biomanufacturing.Technical: Biological organisms are capable of producing chemicals, materials and molecular machines that far exceed our engineering capabilities. Underlying these abilities are the unique properties of proteins, exquisitely evolved for function, allowing precise positioning of atoms and chemistries. Designing novel proteins is difficult because of our still incomplete understanding of how proteins fold for a given primary amino-acid sequence. In this project, researchers will apply principles of synthetic biology to define and modularize building blocks that can be combined in rational ways to enable control of 3D positioning in designed macromolecular structure. Members of the consortium have advanced design and engineering principles for polypeptide- and DNA-based nanostructures and developed next-generation gene synthesis to facilitate high-throughput approaches. The team will build on these foundations to engineer bio-macromolecular assemblies with shapes and functions of unprecedented complexity. They will deliver an expanded toolbox of polypeptide building elements; rules, design principles and methods for constructing complex bionanostructures; and routes to nucleic acid/ polypeptide-hybrid platforms for the community of synthetic biology. The project will expand the limits of the designed polypeptide and nucleic acid/protein hybrid providing a platform to facilitate their use in a wide range of biomanufacturing applications.