Phosphosphingolipids are a vital class of membrane lipids implicated in a multitude of cellular functions, ranging from bilayer stability, lipid raft formation, and membrane trafficking to the regulation of cell growth and apoptosis.
Of particular interest is the sphingomyelin cycle, a putative sphingolipid signalling system analogous to the well-known second messenger phosphoinositide pathway. Whereas sphingomyelin provides an abundant phosphosphingolipid in mammals, many animals synthesise ceramide phosphoethanolamine instead of, or in addition to sphingomyelin.
The host institute recently identified a family of sphingomyelin synthases and a related group of candidate phosphoethanolamine synthases, hence providing a unique starting point to further uncover the organising and regulating potential of phosphosphingolipids in animal cells.
In the present proposal, knowledge of these enzymes will be exploited to manipulate either the rate or the site of phosphosphingolipid synthesis, and to analyse the impact of these manipulations on the growth, secretory competence and compartmental organisation of animal cells.
Moreover, the proposal seeks to explore the possibility that animals lacking sphingomyelin are equipped with a ceramide phosphoethanolamine cycle analogous to the sphingomyelin cycle.
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