The Chemistry of Life Processes Program in the Chemistry Division is funding Professor Matthew Pratt at the University of Southern California to investigate how a specific chemical modification of proteins changes the chemical and biochemical properties of the proteins. In addition, Dr. Pratt and his team wish to learn how the chemical modification, which occurs by addition of a sugar molecule to amino acid sites in the proteins, is associated with the death of biological cells. This sugar modification of certain proteins inside cells has been shown to lower the likelihood of a particular type of cellular death, called apoptosis. This programmed cell death pathway is fundamental to a wide variety of biological events and outcomes. Even though sugar modification of proteins controls programmed cell death, the exact details regarding the chemistry and biochemistry are unknown. The experiments proposed here test two relatively unexplored potential paths where the sugar modification may change the behavior of specific proteins, which lowers the likelihood of programmed cell death. Through parallel activities, experiments from the research project are integrated into an outreach program to create a protein science laboratory for high school students.
This research project aims to understand the direct consequences of O-GlcNAc modification on apoptosis-linked proteins. To accomplish this goal, synthetic protein chemistry will be used to prepare homogeneous and site-specifically modified proteins for biochemical study. This method enables the precise construction of O-GlcNAc modified proteins through the combination of recombinant protein expression and peptide synthesis. This method will be exploited in two ways. First, the effects of O-GlcNAc on an executioner of apoptosis, caspase-6, will be tested. Second, O-GlcNAcylation of the chaperone protein HSP27, which can inhibit apoptosis by preventing protein-protein interactions, will be explored. Information from this study will provide new insights into how O-GlcNAc can inhibit apoptosis.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.