“Defining the molecular basis of phosphoinositide kinases regulation, and their role in disease using an integrated biophysical approach,” by John E. Burke, Assistant Professor, Department of Biochemistry and Microbiology, University of Victoria. Thursday, February 5, 2015 @ 12:30 pm, LSC #3, 2350 Health Sciences Mall.
Lipid phosphoinositides are essential regulators of many cellular processes, including growth, proliferation, membrane trafficking, and cytokinesis. The enzymes that modify these species are frequently misregulated in numerous human diseases. This is emphasised by the fact that one of the most frequently mutated genes in human cancer is the gene for phosphoinositide 3 kinase alpha (PIK3CA). I will discuss our work examining the regulation of phosphoinositide 3 kinases and phosphatidylinositol 4 kinases , and the molecular basis of how disease linked mutations modify their regulation. A specific focus will be on our synergy of X-ray crystallography, Hydrogen deuterium exchange mass spectrometry (HDX-MS), and functional biochemical assays to probe enzyme structure, dynamics, and function. These enzymes all act on membrane surfaces, and I will also focus on our development of novel biophysical tools to examine membrane signalling complexes in their native lipid environment.