We are developing methods to convert bacteriophage T4 tail fiber proteins into self-assembling nanometer scale structures (e.g. nano-fibers, meshes, particles). Native T4 tail fibers (TF) are stiff protein rods approximately 150nm long and 2nm wide. Their component proteins are manufactured and attached to virions in bacterial cells with unrivaled rapidity and dimensional consistency. Our aim is to harness these processes and, using genetic manipulation, to produce rods that are functionalized at predetermined points along their length and that spontaneously assemble into useful two- and three-dimensional structures. We are convinced that this ability to manufacture specific protein based nanostructures with controlled presentation of functional moieties will be of great significance in such varied fields as catalysis, drug delivery and medical imaging.

Our lab is quite interdisciplinary in nature and continues to have a number of successful collaborations with engineers and applied scientists in various fields. Over the next several years our immediate focus is on the atomic level characterization of the native tail fiber and a more complete understanding of the nature and kinetics of the protein-protein and protein-solvent interactions which drive the biological assembly of fibers and the spontaneous, irreversible, but non-covalent, attachment of these components to form larger protein structures. In addition, we plan to continue to create, fold, purify, characterize and assemble mutants of the native fiber that display specific affinity and/or catalytic domains across a range of modified fiber lengths. As a result, skill sets in genetic manipulation, fermentation, protein purification, biophysical characterization of macromolecules and molecular modeling are of particular value to our lab.

Research activity in our lab also encompasses some process and applications development. For example, in conjunction with NSF funding to examine the assembly of TF’s into ‘nanotriangles’, we completed the first phase of a project examining the interaction of tail fibers in solution by computer simulation, in collaboration with the Comuter Science department. The focus of this approach is on optimizing the interactions of fibers with different and specific ‘sticky’ ends. Finding the minimum number of specific ends and conditions that favor the interaction of two, three, four and more unit elements in order to control the geometry of assembled constructs is a significant challenge. We are also interested in how display peptides might interact with the environment and in how such interactions might be monitored non-invasively. The biological nature and unique shape of TFs offer advantages in this area that are potentially useful in bio-sensing and diagnostic applications, among others. These more applied areas are an important part of our vision, and of considerable importance to our long-term success.