BMP is a glycerophospholipid found in intraluminal vesicles of late endosomes/lysosomes and at low concentrations in the circulation. It plays a key role in cellular lipid degradation pathways by stimulating the activity of acidic lipid hydrolases and lipid-binding/transfer proteins. BMP concentrations in tissues and serum increase in genetic and drug-induced lysosomal storage disorders. Despite its central role in lipid sorting and its association with lysosomal dysfunction, little is known about the nutritional regulation of BMP and the enzymes catalyzing BMP synthesis and degradation. PP07/Zimmermann will elucidate the molecular pathways regulating tissue and serum BMP levels in health and disease. This will unveil metabolic relationships essential for the understanding of lipid degradation and sorting in acidic organelles. Specifically, this project will identify and characterize enzymes catalyzing BMP synthesis in mammalian cells and flies, examine whether human subjects with metabolic disorders exhibit aberrant BMP metabolism, and characterize the role of the BMP-hydrolyzing enzyme ABHD6 in BMP metabolism in vivo.
Robert Zimmermann is an established expert in the field of metabolic lipid hydrolases and their functional roles in lipid and energy metabolism. His most important scientific contributions include studies of the functions of HSL and MGL in lipid metabolism and signaling, the discovery of ATGL in TG catabolism, and the identification of CGI-58/ABHD5 as co-activator for ATGL.
Ulrike Taschler is a gifted young scientist and an established expert in the field of lipid signaling. Her most important scientific achievements include the generation and characterization of mice lacking the monoacylglycerol hydrolases MGL and ABHD6. She intensively studied the role of these enzymes in lipid metabolism, endocannabinoid signaling, and metabolic disease.