Lipids are central for life, both on the level of a single cell and of complex organisms. While in the past research in cell biology has focused on proteins and their functions, the importance of lipids as active players has attracted much interest recently. A starting key observation is the fact, that the cellular lipid pool consists of several hundred individual lipid species that are different in hydrophobic side chains and hydrophilic head groups. The challenge is to understand this amazing diversity with respect to organization and function in the context of a living cell.

We focus on three central basic questions:

• How is the lipid composition of a cell or a tissue regulated?
• Where are certain lipid species found in a cell and how is their targeting achieved?
• How do lipids interact with proteins to modulate their function?

To answer these questions, we have developed innovative technologies that we are now applying to study the function of lipids in living cells.

New technologies:

Polyene lipids.
A novel fluorescent lipid-tag to study lipid localization and targeting.

Photocholesterol and photo-PC.
These photocrosslinking lipids are the best tools available today to study the interaction of lipids with proteins in living cells.

Photo-leucine and photo-methionine.
New tools for protein-protein photocrosslinking in living cells, especially suited to study interactions of membrane proteins.

Suchanek, M., A. Radzikowska, and C. Thiele
Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells.
Nature Methods, 2005. 2(4): p. 261-268

Kuerschner, L., C.S. Ejsing, K. Ekroos, A. Shevchenko, K.I. Anderson, and C. Thiele
Polyene-lipids: A new tool to image lipids.
Nature Methods, 2005. 2(1): p. 39-45

Panakova, D., H. Sprong, E. Marois, C. Thiele, and S. Eaton
Lipoprotein particles are required for Hedgehog and Wingless signalling.
Nature, 2005. 435(7038): p. 58-65

Matyash, V., et al.
Sterol-Derived Hormone(s) Controls Entry into Diapause in Caenorhabditis elegans by Consecutive Activation of DAF-12 and DAF-16.
PLoS Biol, 2004. 2(10): p. e280

Thiele, C., M.J. Hannah, F. Fahrenholz, and W.B. Huttner
Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles.
Nature Cell Biol, 2000. 2(1): p. 42-9

Schmidt, A., et al.
Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid.
Nature, 1999. 401(6749): p. 133-41