Structure of membrane
Cell Polarity, homeostasis
The membrane lipid composition of Drosophila depends is strongly influenced by dietary lipids – like humans, they cannot desaturate fatty acids beyond the D9 position, and their membranes only contain polyunsaturated fatty acids when they are able to feed on plant material. Since they are sterol auxotrophs, membrane sterol composition can also be controlled by diet. This provides an opportunity to study how membrane composition affects signalling and physiology in vivo in a powerful genetic model. We’ve shown that dietary effects on membrane composition alter the temperature dependence of membrane fluidity and the viable temperature range (Brankatschk et al., 2018). They also alter organism-wide insulin signalling even on diets with the same caloric content (Brankatschk et al., 2014).
Now we plan to explore in more detail how diet influences the biophysical properties of membranes, and the role of dietary lipids and lipid trafficking in regulating two signalling pathways: the insulin pathway and the Hedgehog pathway.
Previously, we showed that the fluidity of liposomes prepared from total membranes of yeast versus plant-fed Drosophila responded differently to temperature. We will now work with Jitu Mayor’s group to refine this analysis. We will exploit the imaging methods they have developed to look at lipid microdomain dynamics and cortical dynamics in the plasma membranes of hemocytes prepared from Drosophila on different diets.
We are also working with the Coskun group to investigate how membrane lipid composition influences sensitivity to insulin ligands in explanted Drosophila tissues, and the role of insulin signalling in regulating cell metabolism in response to temperature.
Finally, we are working with André Nadler to study the trafficking of endocannabinoids – signalling lipids with an important function in regulating the Hedgehog pathway.
Brankatschk M, Gutmann T, Knittelfelder O, Palladini A, Prince E, Grzybek M, Brankatschk B, Shevchenko A, Coskun Ü, Eaton S. A Temperature-Dependent Switch in Feeding Preference Improves Drosophila Development and Survival in the Cold. Dev Cell. 2018 Sep 24;46(6):781-793.e4.
Çiçek IÖ, Karaca S, Brankatschk M, Eaton S, Urlaub H, Shcherbata HR. Hedgehog Signaling Strength Is Orchestrated by the mir-310 Cluster of MicroRNAs in Response to Diet. Genetics. 2016 Mar;202(3):1167-83.
Bilgin M, Born P, Fezza F, Heimes M, Mastrangelo N, Wagner N, Schultz C, Maccarrone M, Eaton S, Nadler A, Wilm M, Shevchenko A. Lipid Discovery by Combinatorial Screening and Untargeted LC-MS/MS. Sci Rep. 2016 Jun 17;6:27920.
Lavrynenko O, Rodenfels J, Carvalho M, Dye NA, Lafont R, Eaton S, Shevchenko A. The ecdysteroidome of Drosophila: influence of diet and development. Development. 2015 Nov 1;142(21):3758-68.
Khaliullina H, Bilgin M, Sampaio JL, Shevchenko A, Eaton S. Endocannabinoids are conserved inhibitors of the Hedgehog pathway. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3415-20