Professor Jason Shear of the University of Texas Austin will work with Professors Eric Anslyn and Andrew Ellington on a project in bioanalytical chemistry supported by the Analytical and Surface Chemistry Program. The PI initiated a gated ultra-fast electrophoretic separations method in his previous award in the CAREER program. The idea is to cage a molecule, activate it photochemically, do a separation in microseconds and then detect the compounds using light in a time-of-flight analogy. This project centers on the application of that method to the problem of protein folding. Novel photochemical triggering with the help of site-directed mutagenesis to achieve the desired chemistry are being explored. Two model proteins will be used: cytochrome c and apomyoglobin. The project combines analytical and physical chemistry, organic synthesis and molecular biology to develop and evaluate a novel instrument for fast and sensitive detection of protein folding processes.
The research is motivated by the question of how protein sequence specifies conformation, a major unanswered question in biology. There is thus a great need for quantitative information about the energetics and dynamics of protein refolding. The role of misfolded proteins is implicated but not well understood in a growing number of diseases such as Alzheimer's disease.
