Phosphoinositides Provide Unique Insights into Cell Biology and Pathophysiology Abstract Area of Science: 07 Molecular and Cellular Biology The phosphoinositides are a group of lipid signaling molecules that are known to play critical roles in regulating cell proliferation, apoptosis, metabolism, autophagy, signal transduction, and membrane trafficking. They play important roles in the pathophysiology of inflammatory disease, cardiovascular disease, neurologic disease, type 2 diabetes mellitus, and many cancers that together afflict the majority of Americans. Understanding the phosphoinositides is key to understanding a wide range of cell biology and human pathophysiology. Nevertheless, our understanding of their range of functions and mechanisms of action remains rudimentary at best. Here, I propose to develop three novel approaches to study the phosphoinositides in a systematic and unbiased way. The three approaches together provide tremendous synergy. Using these novel approaches my preliminary data has already identified new, surprising functions for the phosphoinositides. Once systematically applied, these approaches have the real potential to revolutionize our understanding of the functions of the phosphoinositides and the diverse biological processes and disease states that they control.
