Research & Publications
The "central dogma" is a phrase coined in 1958 by Francis Crick to describe the universal observation that DNA codes for RNA which codes for proteins. Implicit in this description is the tenet that a linear chain of amino acids represents a complete code for a molecular structure. The study of protein folding is predicated on two observations. First, the functional structure of a protein resides at the free energy minimum of all possible conformations. Second, that despite an astronomical number of possible configurations, proteins successfully and independently adopt the functional one in a finite amount of time.
That normally soluble proteins are capable of aggregating is a well known frustration. Careful analysis, however, reveals that in many instances of disease, the aggregates are actually highly structured. These aggregates are typically called amyloid fibers and are defined by the presence of a central core of ?-strands stacked at right angles to the long axis of the fiber. The initial formation of such structures is a rare event. However, once present, fibers template and appear to catalyze their own formation. The resultant structures are exceptionally resistant to degradation and disassembly by chemical or proteolytic means. Projects currently underway are therefore focused on model peptides, islet amyloid polypeptide from type II diabetes, and b2 microglobulin which forms amyloid deposits in renal failure patients on dialysis therapy. Our approaches are kinetic, thermodynamic and structural in scope, enabling our investigations to be conducted at a molecular level.