Single molecule biophysics of protein amyloids

Many proteins self-assemble to form 1-dimesional structures called ‘amyloid fibrils’. Proteins amyloids are involved in many diseases such as Alzheimer’s and Parkinson’s diseases. On the other hand microorganisms such as bacteria synthesize amyloid fibrils to form biofilms. Biofilms help bacteria to withstand harsh environments such as high dosage of antibiotics. In my lab we are interested to understand the molecular mechanism of amyloid formation. We use an array of biophysical techniques such as fluorescence spectroscopy, FRET, anisotropy, circular dichroism, atomic force microscopy (AFM) and the calorimetric techniques to characterize the structural changes and the self-assembly or disassembly of the amyloid species. In addition we are building single molecule sensitive techniques such as Fluorescence Correlation Spectroscopy (FCS) and single molecule FRET (smFRET) for quantitative characterization of the early events of protein aggregation.

Role of indigenous proteins of amyloid aggregation

Several functionally important proteins such as the chaperones and apolipoprotein E have been found to influence amyloid aggregation in vivo. For example the small heat shock proteins (HSPs) are known to be protective while e4 isoform of ApoE is the strongest risk factor in Alzheimer’s disease. We will use the single molecule fluorescence techniques including super resolution microscopy such as STORM to characterize these interactions with monomeric, oligomeric and the fibrillar species.