| Project Detail |
Many proteins self-assemble into regular, shell-like, polyhedral structures. Protein capsids are useful, both in nature and in the laboratory, as molecular containers for diverse cargo molecules, including proteins, nucleic acids, metal nanoparticles, quantum dots, and low molecular weight drugs. They can consequently serve as delivery vehicles, bioimaging agents, reaction vessels, and templates for the controlled synthesis of novel materials. Here, we will apply our experience with protein design and laboratory evolution to extend the properties of protein containers to create practical, non-viral encapsulation systems for applications in the test tube and in living cells. Specifically, we will adapt the icosohedral cage structures formed by Aquifex aeolicus lumazine synthase (AaLS) to engineer increasingly sophisticated supramolecular complexes for use as delivery vehicles, nanoreactors and, ultimately, as bacterial organelles. Our principal aims are to: (a) tailor AaLS capsids for selective encapsulation of a broad range of macromolecular guests; (b) develop AaLS capsids as delivery vehicles for medical and imaging applications; (c) design simplified, functional mimics of carbon-fixing carboxysomes; (d) evolve redox active organelles for metabolizing aliphatic alcohols; and (e) engineer artificial organelles for the detoxification of polychlorinated phenols. We anticipate that these experiments will lead to a deeper understanding of the principles underlying the construction, function and evolution of natural protein microcompartments. At the same time, they will establish powerful strategies for creating tailored assemblies for practical applications in delivery and catalysis.
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