Amyloids in disease, functions and in nanobiotechnology
Phase diagram: Many proteins and peptides self assemble to amyloid fibrils and phase separate from the soluble state. Phase transition is dependent on multiple factors such as sequence of the protein, temperature and the solution conditions. We employ various biophysical techniques such as single molecule fluorescence, light scattering techniques and, light, electron and atomic force microscopy to characterize the different phases of the amyloid proteins. Our goal is to construct the phase diagram to obtain a quantitative picture of the protein self assembly.
Figure 1: A schematic representation of the phase diagram of amyloid proteins adapted from Schmit et al, Biophysical Journal, 2011.
Role of small molecules and endogenous proteins on the phase diagram: Several small molecules and endogenous proteins are known to alter the aggregation behavior of clinically important proteins. We are interested to understand the mechanism of the these interactions by using the phase diagram approach.
Figure 2: Effect of apolipoprotein E adapted from Garai et al, Biochemistry, 2014.
Effect of sequence co-variations in the phase diagram of the curli proteins : Many bacteria produce curli which are amyloid fibers of curli proteins. The curli are functional amyloids playing important roles in bacterial biofilm formation. The amyloid protein CsgA is the major and CsgB is the minor component of the curli fibers. However, there are large variations in the sequences of both CsgA and CsgB across different bacterial species. We are interested how the natural variations in the sequences of these influence their amyloid formation.
Figure 3: E. Coli curli fibers. Adapted from Evans and Chapman, BBA, 2014.
Design and synthesis smart nanobiomaterial using protein self-assembly: The dimension of the amyloid fibers and their high stability makes them suitable candidate for development functional materials. We are working to develop protein hydrogels and metal nanowires using amyloids as template.
Figure 4: Schematic representation of folding, self-assembly and gelation of a peptide. Adapted from Gungormus et al, Biomaterials, 2010.