Novo Nordisk Fonden - Novel Regulatory Mechanisms of Ceramide Synthesis

The ability to synthesize complex lipids such as ceramides and sphingolipids is a fundamental property of all cell types. These lipids are essential components of all cells, where they not only function as structural entities, but also as important signaling molecules. Despite these fundamental functions, it is still not known how cells and organisms control and regulate the level of ceramides and sphingolipids. We have recently identified, to our knoweledge, the first regulator of the biosynthesis of ceramides. This regulator, acyl-CoA-binding protein (ACBP), stimulates ceramide synthases both in vitro and in vivo. The purpose of this application is therefore a) to understand the genetic interaction between ACBP and selected ceramide synthases in mammals b) to identify direct interactions between ACBP and ceramide synthases and c) understand the relationship between structure, function and activity of ACBP and ceramide synthases. For these purposes we will use mice lacking ACBP and selected ceramide synthases, and complement these studies with interaction studies in cell cultures and biochemical analyses.