Webb, B.A., Dosey, A.M., Wittmann, T.M.., Kollman, J.M., and Barber, D.L. "The essential glycolysis enzyme phosphofructokinase-1 assembles into filaments." Journal of Cell Biology, 216, 2305-2313.
Webb, B.A., White, K.A., Grillo-Hill, B.K., Schönichen, A., Choi, C., and Barber, D.L. (2016) "A Histidine Cluster in the Cytoplasmic Domain of the Na-H Exchanger NHE1 Confers pH-sensitive Phospholipid Binding and Regulates Transporter Activity". Journal of Biological Chemistry, 291, 24096-24104.
Webb, B.A.*, Forouhar, F.*, Szu, F., Seetharaman, J., Tong, L.†, and Barber, D.L.† (2015) "Human phosphofructokinase-1 structures show subunit interfaces and cancer mutation effects". * equal first authors. Nature 523, 111-114.
Grillo-Hill, B., Webb, B.A., Barber, D.L. (2014) “Ratiometric Imaging of pH Probes” Invited chapter in Quantitative Imaging in Cell Biology", Edited by Waters, J. And Wittmann, T. Methods in Cell Biology, 123, 429-48.
Choi, C., Webb, B.A., Chimenti, M., Jacobson, M.P., Barber, D.L. (2013) "A Molecular Mechanism For pH Sensing by FAK In Focal Adhesion Remodeling". Journal of Cell Biology 202(6), 849-59.
Webb, B.A., Chimenti, M., Jacobson, M.P., and Barber, D.L. (2011) "Dysregulated pH: a perfect storm for cancer progression". Nature Reviews Cancer 11(9), 671-677
Schönichen, A., Webb, B.A., Jacobson, M.P., and Barber, D.L. (2013) "Considering Protonation as a Posttranslational Modification Regulating Protein Structure and Function". Annual Reviews in Biophysics. 42, 289-314.
• Protein structure/function
• Cell biology of metabolic enzymes
Description of Research
The enzymes and pathways controlling intermediary metabolism for energy production, nutrient utilization, and biomass synthesis play critical roles in cellular homeostasis. Dysregulated metabolic enzymes and pathways are now considered central to diseases such as cancer, diabetes, and neurodegenerative disorders. We currently have limited knowledge of the spatial and temporal dynamics of metabolic enzymes in cells, which is critical for understanding metabolic flexibility in normal cells and aberrant metabolism in diseases. Research in Webb lab is focused on understanding the cell biology of metabolic enzymes.
We are currently addressing questions regarding the localization, regulation, and structure/function of enzymes in the glycolytic pathway. Glycolysis is an ancient metabolic pathway for processing glucose into pyruvate, generating energy as well as anabolic building blocks. Glycolytic enzymes function as highly regulated molecular machines that fine-tune the rate of glucose utilization and are dysregulated as well as mutated in cancer and other diseases. Current projects include determining the regulation and functional significance of filament formation by the glycolytic ‘gate-keeper’ enzyme phosphofructokinase-1 (PFK1), the mechanism and significance of a glycolytic metabolon at the plasma membrane, and significance and molecular mechanism of disease-associated somatic mutations to PFK1. Students may learn techniques including live-cell and immunofluorescent microscopy; cell culture; protein expression and purification; structure/function analysis; enzymology; electron microscopy.