Professor of Biology
B.S., Chemistry, Southampton College of Long Island University
Ph.D., Biochemistry, Stanford University
My laboratory is interested in applying protein design principles to the study of polymerizing systems. Two general areas that we are exploring are: (1) polymerizing systems for biomaterials design; and (2) polymerizing systems as models for protein aggregative disease. We are interested in the creation of novel biomaterials. We have focused on using the coiled-coil structural motif as a model system for creating 1D polymers that can be decorated with different chemical functionalities to create electronically conducting materials. Recently, we have found a way to use the coiled coil structure to create polymers in the nanoscale size range. We do this by distributing nonpolar residues in a sequence in such a way that forces the stagger of the two helices that make up the coiled coil structure. This staggered intermediate then templates the growth of polymers that range in the nanometer to micrometer size range as seen in afm studies. We are exploring the rules that govern the assembly of these structures, looking principally at how hydrophobic considerations influence polymer growth. We are also exploring how we might further regulate reversible polymer assembly in response to specific environmental cues, such as metal binding or light. Incorporation of porphyrin derivatives (both by covalent and noncovalent approaches) is being explored to impart electronic functionality. We are also interested in understanding the role of polyglutamine repeats in the problem of protein aggregation in diseases such as Huntington's disease. We are interested in developing a detailed understanding of the molecular mechanism of aggregation in which we will probe the importance of hydrogen bonding between glutamines in the polymer assembly process. We have developed a beta-hairpin model that will allow precise control over the assembly of early folding intermediates. We hope to probe the role of glutamines in beta-hairpin folding and stability and in folding and stability of facial and lateral assembly processes. One face of the hairpin contains glutamines while the other face has lysines, so that we can use pH to control lateral and facial assembly kinetics and stability. Preliminary data for a variant of this hairpin system can form short fibrils, as evidenced by AFM measurements. The dominance by short fibrils suggests that we will be able to control assembly in order to capture and study early assembly intermediates. We synthesize peptides on the order of 21-35 amino acids in length to study polymerization properties. Students can expect to use sophisticated biophysical tools such as circular dichroism spectroscopy, analytical ultracentrifugation, atomic force microscopy, and dynamic light scattering, to characterize the structure of these peptides. These projects are highly interdisciplinary efforts involving collaborations with faculty in the Chemistry, Physics, and Math Departments here at Haverford College.