Transport and function of sterols and sphingolipids in Hedgehog signaling in primary cilia
Name of applicant
Daniel Wüstner
Title
Professor
Institution
University of Southern Denmark
Amount
DKK 7,228,000
Year
2023
Type of grant
Semper Ardens: Accomplish
What?
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.
Why?
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.
How?
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.