The overall goal of the SFB LIPID HYDROLYSIS consortium is to assemble Austrian research groups with the strongest expertise from Graz and Vienna to investigate the biochemistry, cell biology, and physiology of lipid degradation pathways. The biological significance of known hydrolytic lipid degradation processes and the crucial role of lipid hydrolases are evident. They contribute to central metabolic pathways supplying energy substrates, provide important building blocks for the synthesis of lipids, and generate or degrade signaling lipids that regulate lipid and energy homeostasis at multiple levels. Considering these critical roles in lipid and energy metabolism, it is not surprising that dysregulation or dysfunction of lipid hydrolysis contributes to the pathogenesis of numerous metabolic diseases. Some of the involved pathomechanisms are known, but many remain obscure.
The SFB LIPID HYDROLYSIS consortium proposes to pursue two basic methodological strategies to better understand how intracellular lipid hydrolases direct lipid degradation pathways:
- In a hypothesis-driven approach, we will focus on the regulation and physiology of lipid hydrolases involved in cytosolic and lysosomal degradation of neutral lipids.
- In a discovery-driven approach, we will go beyond known enzymes and pathways to identify and characterize a maximal number of lipid hydrolases in the mammalian genomes. The consortium will utilize innovative screening platforms, mathematical modeling techniques, biophysical methods, and structural biology as well as genetically modified mouse models to identify and expansively characterize the biochemical and (patho)physiological functions of predicted and established hydrolytic enzymes and their regulators.
The objectives of the SFB LIPID HYDROLYSIS focus on the identification of unknown lipid hydrolases, the biochemical characterization and physiological function of established and newly identified lipid hydrolases in model organisms, on the regulation of lipid hydrolysis, and on the pathophysiology of lipid degradation in human disease.