Individual functions of Orm/ORMDL family proteins in membran

Sphingolipids are an important class of fat molecules for the integrity of cell membranes of all eukaryotes, including us humans, but also as simple organisms as budding yeasts. Therefore, the levels of sphingolipids are tightly controlled, and mismanagement of sphingolipid levels is associated with disease in humans. The probably most important regulation happens on the level of the first step of their synthesis by the enzyme serine-palmitoyl-coenzyme A transferase (SPT), and is carried out by a family of small membrane proteins, called OMRDL proteins, which inhibit enzyme activity. Most organisms have more than one gene coding for these ORMDL family proteins (humans have three and our model organism budding yeast has two). They contribute differently to disease states, yet, it is very unclear why cells need more than one of these proteins. In this research project we aim to shed lig ht on the functionally different roles of yeast and human ORMDL proteins in the control of sphingolipid levels and potentially other important membrane components.