Abstract 1946 The long road paved by inositol phospholipids

Cellular organization of eukaryotic cells relies upon compartmentalization of their signaling nodes on special membrane platforms forming the various organelles. Unique lipid composition of the different organelle membranes not only defines their identity but also is critical for the proper assembly and functioning of the protein signaling complexes associated with them. Inositol phospholipids (PPIns), a class of regulatory lipids, play a critical role in defining membrane identity and forming membrane microdomains with unique signaling properties. My long research career has been devoted to understanding the role of PPIns in cellular signaling, membrane trafficking and lipid metabolism. In this Award lecture, I will review some of the critical discoveries that defined my research interest and guided me to explore new territories. I will also highlight recent developments in the PPIns lipid membrane biology field, namely how phosphatidylinositol (PI) 4-phosphate (PI4P) gradients drive non-vesicular transport of several structural lipids against their concentration gradients at membrane contact sites (MCSs). Since these processes depend on the delivery of PI from its site of synthesis in the ER to the membranes where PI4Ks convert them to PI4P, our recent efforts have been focused on the question of how PI synthesis and PI transport systems provide the means of proper PI delivery to their other membrane destinations. I will end by reviewing our approach to generating and using molecular tools to visualize and manipulate PI metabolism and demonstrate how such tools can help us better understand the central role of PPIns in defining the overall lipid landscape of eukaryotic cells. Dr Balla's research is supported by the Intramural Research Program of NICHD