Drosophila melanogaster body fat regulation by store-operated calcium entry

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Lipid metabolism homeostasis is a fundamental and universal property of animal organisms. Misregulation of this homeostasis causes severe body fat storage disorders such as obesity in organisms as diverse as Drosophila flies and humans. Arguably, unhealthful lifestyle changes in genetically predisposed populations propel the recent human obesity pandemics. Yet the understanding of the genetic architecture, which predisposes organisms to obesity, is incomprehensive. We recently employed the Drosophila model organisms to reveal for the first time that misregulation of genes, which govern store-operated calcium entry (SOCE) causes severe obesity in flies by hitherto unknown mechanisms. This project proposes the functional characterization of the SOCE core component Stromal interaction molecule to identify the physiological, cell biological and molecular basis for SOCE-dependent body fat regulation. This project will not only provide important insights into how calcium signalling in lipid storage tissue contributes to body fat control in the fly. As SOCE is evolutionarily conserved between flies and man, funding of the proposed project promises novel diagnostic and therapeutic perspectives for human obesity.