SBLIME · Systems Biology of Lipids Metabolism

Lipids are a group of biomolecules found in every living cell, being the main structural components of cell membrane. Despite being so widespread, lipids are the most elusive among the biomolecules, because of the difficulty they present to be analyzed with most of classical biochemical techniques. Nevertheless, recent advancements in high-resolution chromatography and mass spectrometry have started to throw light on this large class of compounds (the full lipidome is suspected to be of the order of hundred thousand species). Their fundamental role in cellular and organism physiology, both in health and disease, has started to be appreciated. In particular new functions of lipids are being discovered, including regulatory and signaling functions. Their deregulation has been recognized as a key factor in several metabolic diseases, ranging from diabetes, obesity, hypertension, to coronary, neurological and Alzheimer's diseases. Therefore, it necessary to investigate how lipids function within the cell physiology and to study the coupling between global metabolism and lipid metabolism. Systems Biology provides the natural framework for such a integrated study of lipid metabolism and biosynthesis pathway. We propose to develop a set of mathematical and numerical tools useful to investigate the structure and regulation of the lipid biosynthesis pathway and to identify the key parameters (enzyme activities and substrate concentrations) responsible for the alteration of the distribution of lipids. The results of this analysis will be communicated to experimentalists and the collection of further experimental evidence will be concerted. Collected data will be used, in turns, to refine the models. The interaction between theory and experiments will provide new insight and quantitative understanding of the interplay between lipids metabolism and global cellular functions and its implication in health and disease.