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Molecular principles guiding lipid structure and function of autophagosomes


This project combines advanced imaging, proteomics, and lipidomics with computer modeling of dynamic membranes to gain deeper insights into how lipid composition influences autophagosome membrane architecture and function. We will employ innovative isolation methods to purify autophagosome membranes under different cellular conditions, e.g., under altered lipid homeostasis, and focus on the impact of detailed lipid profiles and distinct phospholipids (e.g., sphingomyelins) on emergent properties of the autophagosome membrane. Additionally, this project aims to resolve the specific role of ATG9A and its scramblase activity in active modulation of the lipid architecture to regulate autophagosome structure and function.



Modeling & simulations of autophagosome membranes. The defined lipid profile and composition (left) provides the molecular identity for the phagophore membranes and autophagosomes. A) MD simulation snapshot of the ER membrane with embedded membrane proteins shows bilayer fluctuations (left). Lipid composition controls several interdependent mechanical properties and thereby affects the emergent functions of the membrane (right). Parts of this figure have been modified and adapted from Ben-Dov & Korenstein, 2013; Cebecauer et al., 2018; Maeda et al., 2020. B) Sphingomyelin lipids enriched in autophagosomes can mediate specific lipid-lipid interactions with PC and sterols resulting in formation of ordered laterally segregated nanodomains (left). Further, SMs could form inter- & intramolecular H-bonds stabilizing the nascent clusters (right). C) Structure of ATG9A trimers shows central & lateral pores for lipid scrambling (left). In silico assay for scramblase activity of membrane proteins employs chemical

 Dr. Ramachandra bhaskara

Institute of Biochemistry II

GU Frankfurt
Theodor Stern Kai 7
60590 Frankfurt a. M.
Office: +49 69 798 42710



Institute for Pathobiochemistry
University Medical Center of the Johannes Gutenberg University Mainz
Office: +6131 39-23185

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