Transport and function of sterols and sphingolipids in Hedgehog signaling in primary cilia
Navn på bevillingshaver
Daniel Wüstner
Titel
Professor
Institution
University of Southern Denmark
Beløb
DKK 7,228,000
År
2023
Bevillingstype
Semper Ardens: Accomplish
Hvad?
Primary cilia are small antenna-like membrane protrusions, which harbor protein components of various signaling pathways, including Hedgehog signaling. Lipids, such as cholesterol, oxysterols and sphingolipids, have been shown to be essential for Hedgehog signaling, but the underlying molecular mechanisms are not understood.
Hvorfor?
Lipids have long been seen solely seen as building blocks of cell membranes, but their central role in controling protein function becomes slowly apparent. How specific lipid molecules regulate proteins is a central open question in cell biology. We expect that the outcome of this project will fundamentally change our understanding of lipids in cell signaling and in development of diseases.
Hvordan?
We will combine light-controlled activation and imaging of lipids with single molecule tracking of lipid-interacting proteins, proteomics, chemical biology and biophysical modeling to uncover the function of cholesterol, oxysterols and sphingolipids in Hedgehog signaling in primary cilia. This multi-disciplinary effort will provide novel insight into protein-lipid interactions in living cells.