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1) Utilization of protein cages as platforms for making functional nanomaterials

Protein cage nanoparticles (PCNs) such as viral capsids and ferritin have been considered promising platforms for developing functional nanomaterials due largely to the following reasons: 1) As the protein cages are gene products, their size and structure are extremely homogeneous, 2) The interior cavity of cages can be utilized for templated synthesis of well-defined nanoparticles, and 3) They accommodate the introduction of functionality such as cell-targeting capability, either chemically and genetically. The Uchida laboratory is developing protein cage architectures as a means to encapsulate and sequester guest molecules including inorganic nanoparticles as well as organic molecules and proteins. These nanomaterials have a great potential with a range of applications from catalysis to biomedicine.

2) Controlled assembly of protein building blocks into higher order structures

The assembly of functional nanoparticles into ordered three-dimensional arrays is a promising strategy for developing novel materials with properties arising from interactions between individual nanoparticles. The use of protein-based nanoparticles as building blocks is an exciting new direction because proteins exhibit diverse and sophisticated functionalities, which are often difficult to realize in synthetic molecules. However, protein crystallization is a laborious procedure and usually needs to be optimized in a protein dependent manner and thus difficult to generalize. Here, derived from the concept of metal-organic frameworks (MOFs), I will establish a new strategy for constructing protein-based array materials through directed self-assembly of protein cage nanoparticles (PCNs) and linker proteins with structurally regulated coordination geometry.

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3) Exploring interaction between proteins and inorganic materials to design new hybrid materials

When in contact with biological fluids, inorganic materials (and any other exogeneous materials) are rapidly covered with a layer of biomolecules so-called biomolecular corona layer. The corona confers a new surface and significantly alters the cellular response to the material and the biodistribution of the material in vivo. We exploit this passive process as an opportunity to form a designed corona layer around inorganic materials. We expect that a stable corona layer can be formed around an inorganic material ex vivo by using rationally engineered proteins, that leads to the development of inorganic-organic hybrid materials with new functionalities.

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