NSF/DMR-BSF: Supramolecular mutualism in Functional Nucleic acid and Peptide Co-assemblies

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Non-technical: This NSF/BSF award by the Biomaterials program in the Division of Materials Research to Emory University is a study in understanding the emergence of chemical evolution for the design and preparation of biomimetic systems as complex as artificial cells and tissues. This award is co-funded by the following programs: 1) BMAT program in the Division of Materials Research; 2) Catalysis and Biocatalysis program in the Division of Chemical and Bioengineering, Environmental, and Transport Systems (ENG); and 3) Global Venture Funds in the Office of International Science and Engineering. This collaborative research combines complementary expertise of scientists in US and Israel. While man-made processes and products are typically passive and static, those found in the living world are active and dynamic. To better understand this dynamic, active and complex system, this project will use radically different approaches in areas ranging from materials sciences in the design and study of complex systems for the construction of self-organizing, multi-component chemical networks for storage and amplification of molecular-scale information. This award will design bottom-up synthesis of novel mesoscale assemblies, which in turn will be used to build cooperative interactions between different biopolymer families to achieve the first synthetic mutualistic network for materials research. These studies are expected to result in new materials benefiting biotechnology in diagnostics, gene delivery, drug delivery, etc. As part of this project, new core chemistry classes that blend chemistry, polymers, and materials will be implemented to enhance educational curiosity in supramolecular mutualism. Mesoscale assemblies will be captured in simulations, visually building from blends and block polymers to mutualistic biopolymer networks. Videos will also be developed highlighting the sciences, the humor and the culture of the US and Israeli faculty and students. This project will also be developing novel teaching methods and interdisciplinary materials projects in the newly opened research/learning center - Science Commons - at Emory University. Technical: This collaborative research is focused on designing peptide/nucleic acids based dynamic and active assemblies that can catalyze their own replication. Toward this goal, the project will explore dynamic networks in regulating molecular evolution by: 1) elucidating the structure of nucleic acid/peptide intermolecular and nucleic acid/peptide conjugate assemblies; 2) studying their assembly pathways and defining control factors for assembly (pH, temperature and salt concentration); and 3) characterizing the mutualistic functions enabled by these assemblies and co-assemblies. The proposed iterative structural and functional analyses of these composites are expected to provide sufficient insight in constructing a synthetic digital-to-analog converter with alternative nucleic acid/peptide assemblies. The wealth of information developed on protein and nucleic acid interactions and the structural information that will be provided by these assemblies would allow one to engineer mutualistic behaviors, where cooperative peptide templates would serve as nucleic acid polymerases, and nucleic acid/peptide co-assemblies in catalyzing their own replication. These studies could be the first step in expanding and understanding the supramolecular assembly into self-organizing networks for novel materials. Just as the emergence of the ribosome provided a critical Darwinian threshold for our biosphere, one may see these studies as first set in demonstrating the use of mutualistic polymers and supramolecular catalysts for the creation of intelligent materials. This work is also expected to expand the analytic and modeling methods available for dynamic chemical systems, and for the cross catalytic networks that will serve as a foundation for a synthetic biology, which in turn will ultimately lead to evolutionary strategies for the discovery and optimization of functional materials.