Molecular Determinants of Sterol-Sphingolipid-Protein interactions in Living Cells and Organisms (Lipid Specific)
Sterols and sphingolipids are major lipids of the plasma membrane and endocytic pathways found almost exclusively in eucaryotes and differ in their specific structure between species. While the concept of lipid rafts is consistent with a number of findings from model and cell membranes, this hypothesis is not sufficient to explain the biologically observed interdependence between sterol and sphingolipid structures, nor does it help to predict which specific protein-lipid interactions may regulate functions at the cell and tissue level. The molecular determinants governing specific sterol-sphingolipid-protein interactions in cell membranes cannot be predicted from studies in model membranes, where the structural complexity of biomembranes cannot be accurately reconstituted.
This project proposed to use instead experimentally amenable model organisms (yeast, flies and worms) as platforms to identify key structural elements and functional consequences of sterol-sphingolipid-protein interactions. Parallel studies in mammalian cells and tissues will focus on selected aspects of sterol-sphingolipid-protein affinities in questions relevant for human physiology and pathology. A wide combination of state-of-the-art techniques, including genetics, systematic biological phenotyping, chemical synthesis of sterols and sphingolipids, lipid imaging in living cells/tissues, and mass spectrometry for lipid analysis will be employed.
Project Leader:
Professor Elina Ikonen, University of Helsinki, Finland
Principal Investigators:
Professor Howard Riezman, University of Geneva - Sciences II, Geneva, Switzerland
Dr. Suzanne Eaton, Max Plank Institute for Molecular Cell Biology and Genetics, Dresden, Germany
Dr. Teymuras Kurzchalia, Max Plank Institute for Molecular Cell Biology and Genetics, Dresden, Germany
Professor Patrizia Stoppelli, National Research Council, Naples, Italy
Professor Hans-Joachim Knölker, Technical University Dresden, Dresden, Germany
Associated Partner:
Professor Daniela Corda, National Research Council, Institute of Protein Biochemistry, Naples, Italy
