In earlier work, we isolated components
of the SREBP pathway in Drosophila cells (Fig. 1) and showed
that it could be regulated by palmitate rather than sterols.
We went on to demonstrate that phospholipids, rather than palmitate
itself, are the principle regulatory lipids in flies (Fig. 2).
Our extensive characterization of the SREBP pathway in Drosophila
cells further enabled us to use that system to show that mammalian
Insig proteins were both necessary and sufficient to confer sterol
regulation on the mammalian SREBP pathway.
We then isolated mutant flies lacking
the gene for SREBP and discovered that these animals die at the
2nd-to-3rd larval instar transition. We overcame this lethality by supplementing
the larval diet with extra lipid. Free fatty acids were far more
effective at promoting survival than were more complex lipids (e.g. triglycerides
and phospholipids.) Our ability to recover adult flies lacking
all SREBP function allowed us to show, in collaboration with Sara Cherry
of Norbert Perrimon’s laboratory, that SREBP is essential for the replication of
certain kinds of polio-like viruses.