With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Amy Barrios at the University of Utah to study the newly discovered protein histidine phosphatase family of enzymes. Communication between and within cells is critical in controlling all aspects of cellular activity, including cell growth, cell division, and cell death. One common way that cells communicate signals is by chemically changing proteins by adding or removing a phosphate group. The Barrios research group develops chemical tools that can be used to study the enzymes responsible for removing phosphate groups from proteins, providing insights into cellular mechanisms of communication. This project focuses on the newly discovered family of histidine phosphatase enzymes. The chemical tools being developed in this project have the potential to provide valuable insight into the roles played by these enzymes in cellular signaling and thus, provide fundamental insights into this poorly studied, but critically important, mode of cellular signaling. Key to the success of the project is the inclusion of undergraduate, graduate, and postdoctoral researchers from diverse backgrounds with the goal of broadening participation in research. In addition, Dr. Barrios is committed to mentoring junior scientists and is working to create a university-wide framework to provide support and career development opportunities for postdoctoral researchers.
Reversible protein phosphorylation is widely used in biology to regulate protein-protein interactions and cellular signaling pathways. While phosphorylation at serine, threonine and tyrosine in mammalian cells is widely recognized as critical, histidine phosphorylation is much less well understood. Recently, three mammalian histidine phosphatases have been discovered. These enzymes play critical roles in regulating ion channels, T-cell receptor signaling, and G-protein coupled receptor signaling, with additional, yet-undiscovered roles likely. Researchers in the Barrios lab are developing chemical probes that will facilitate monitoring the activity of individual histidine phosphatases both in vitro and in cells. Specifically, the Barrios lab is developing selective substrates and inhibitors of histidine phosphatase activity that can be used to address key questions about histidine phosphatase biology. This approach can readily be applied to almost any member of the histidine phosphatase family of enzymes. The research objectives are integrated with work aimed at broadening participation in science by engaging undergraduate, graduate, and postdoctoral researchers from diverse backgrounds and with efforts to enhance the framework for postdoctoral training through the development of programs that support early-career scientists.
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.
