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Proteolipidomic characterization of the regulatory circuitry of global lipid metabolism

Objective

The lipidome of eukaryotic cells consists of hundreds to thousands of lipid species that constitute membranes, store metabolic energy and function as bioactive molecules. The physiological importance of lipid complexity is demonstrated by numerous diseases with inherent perturbations of lipid homeostasis including obesity, atherosclerosis, cancer and neurodegenerative disorders. How lipid complexity affects cell homeostasis and how cells regulate lipid metabolism on a lipidome-wide level remain unclear. The regulatory capacity of post-translational modifications in lipid metabolism is scarcely known, but an increasing body of evidence supports the premise that lipid enzyme activity can be dynamically regulated by protein phosphorylation. The main aim of this project is to functionally map the phosphorylation-dependent regulatory network of global lipid metabolism. To this end, we will develop a mass spectrometry-based proteolipidomics strategy for the yeast Saccharomyces cerevisiae. This platform will be designed for parallel quantitative analysis of lipid flux and the phosphorylation state of virtually all lipid enzymes and the kinases, phosphatases, and accessory regulatory factors involved in the cellular signalling networks. S. cerevisiae uses a relatively simple and conserved network of lipid metabolic pathways and is amenable to genetic manipulation and biochemical analyses, which make it a prime model organism for this study. This systems-level approach will enable us to (i) build a comprehensive regulatory map of global lipid metabolic networks, and (ii) delineate the dynamic regulation of lipid metabolism in key cellular events (e.g. cell division). Moreover, this work will help unravel the molecular design of conserved regulatory pathways of lipid metabolism and serve as a fundament for establishing analytical strategies applicable to studies in higher eukaryotes.

Call for proposal

FP7-PEOPLE-2010-IEF
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Coordinator

SYDDANSK UNIVERSITET
Address
Campusvej 55
5230 Odense M
Denmark
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 220 590,40
Administrative Contact
Ole Nørregaard Jensen (Prof.)