Modeling dominant protein interactions that influence the pathogenesis of protein folding diseases
Santiago Schnell (Department of Molecular & Integrative Biology, Department of Computational Medicine & Bioinformatics, Brehm Center for Diabetes Research, University of Michigan)
(January 27, 2014 3:00 PM - 3:50 PM)
Protein folding diseases occur when a specific protein fails to fold into its correct functional state as a consequence of mutation in the protein amino acid sequence. In this talk, I present a model of the folded and misfolded protein expression, processing and their interactions, which we have used to investigate how protein folding disease phenotypes develop from mutated genotypes. Modeling protein processing as a continuous flow reactor, we found that the pathogenesis of protein folding diseases can be modulated by a combination of the transition time of folded and misfolded proteins in the reactor, the ratio of folded and misfolded protein inflow rates in the reactor and a chemical interaction parameter between folded and misfolded proteins. Our analysis reveals therapeutic strategies targeting the modulation of protein folding diseases, which have been recently explored in cellular and animal models of Mutant INS-gene Induced Diabetes of Youth and Congenital Hypothyroidism with deficient thyroglobulin.