Our laboratory uses the fruit fly, Drosophila melanogaster, as a model system to understand the mechanisms by which animal cells sense the requirements for (and regulate the production of) fatty acids. In mammals, a complicated assemblage of protein machinery, known as the SREBP pathway, is central to these processes.

The SREBPs (sterol regulatory element binding proteins) are membrane-bound transcription factors. When lipid supplies are sufficient, they remain in the membranes of the endoplasmic reticulum - when cellular demand for lipid rises, another protein, SCAP, escorts SREBP to the Golgi apparatus where two different proteases are required to release the transcription factor from the membrane and allow it to travel to the nucleus. There, SREBP binds to sequences in the upstream region of target genes and mediates their increased transcription.

The best studied role of the SREBP pathway in mammals is the regulation of cholesterol uptake and production. The SREBPs are also involved in aspects of fatty acid metabolism as well. This role in fatty acid metabolism is easier to study in flies than in mammals because flies cannot make cholesterol ‘from scratch’ and must get it as part of their diet. Vertebrates are capable of making their own cholesterol as well as fatty acids and have twoseparate genes that encode three different SREBP proteins. By contrast, Drosophila has only a single SREBP gene. In addition, the considerable array of genetic and molecular tools available for Drosophila make it a productive experimental system in which to study fatty acid metabolism.