Research Interests:
Organic, Bioorganic, and Materials
Chemistry --
Self-assembling networks of inorganic
nanocrystals from modified cytoskeletal
proteins, functionalized viral capsids
for drug delivery and 3-D nanomaterial
construction, and new synthetic
methods for
site-specific protein modification
Research in the Francis group is focused on the development of new synthetic methods for the construction of nanoscale materials. The central strategy involves the attachment of new functional components to specific locations on structural proteins, and the subsequent self-assembly of these conjugates into new types of materials with useful electronic and biological functions.
Controlled Growth of Nanocrystalline
Arrays Using Cytoskeletal Proteins
Modern
synthetic methods for the preparation
of inorganic nanocrystals have yielded
promising new components for optical
and electronic device construction.
However, the organization of these
materials into functional assemblies
remains extremely difficult, in part
because the small size of nanocrystals
(2-10 nm) is well below the spatial
resolution of most lithographic techniques.
An alternative approach could be
provided by attaching these nanocrystals
to specific sites on the surfaces
of fiber-forming cytoskeletal proteins,
such as actin. By controlling the
polymerization of the actin conjugates
with additional proteins and small
molecule natural products, specified
locations could be connected with
wire-like arrays of functional materials.
Once constructed, the arrays could
be converted into conductive linkages,
thus providing an entirely new method
for nanoscale circuit construction.
Modified Viral Capsids for the
Assembly of Core/Shell Materials
A
second research area involves the synthesis
of three-dimensional nanostructures from
the self-assembling proteins that form
the outer coats of viruses. For example,
by selectively modifying the top and bottom
faces of the satellite panicum mosaic virus
capsid protein, new types of core/shell
materials could be obtained after assembly.
These structures could be developed into
particles capable of targeting desired
tissue types and releasing their cargo
of drug molecules. Functionalized viral
capsids could also provide new tools for
the investigation of multivalent binding
interactions that occur in biological systems.
New Methods for Site-Selective
Protein Modification
A central
theme in this research program is the modification
of structural proteins in specific locations
in order to achieve homogeneous and predictable
assembly. Site-directed mutagenesis provides
a powerful set of tools for this purpose,
and will be used extensively. However,
there are limitations associated with this
technique, and therefore the development
of new chemical approaches for protein
modification will be pursued as well. This
research will take advantage of the rapidly
expanding set of organic reactions that
can proceed in aqueous solution, and will
utilize asymmetric ligands and catalysts
to enhance the selectivity of protein modifications.
Combinatorial reaction libraries will play
an important role in this research area.
