Regulation of autophagy upon Legionella infection
We will examine the impact of serine ubiquitination on the host autophagic pathway and how this might affect bacterial infection by Legionella. We will perform functional studies to elucidate the contribution of Legionella SidE proteins and RavZ in impairing host autophagy. We will use super-resolution microscopy to study the nanoscale protein organization around the Legionella-containing vacuole, focusing on autophagy, signaling proteins, and ubiquitination. We will develop a functional, spatiotemporal and molecular picture of processes that guard Legionella from autophagy-mediated clearance.
Localization of SidE family member SdeA in A459 cells following infection with Legionella. Upper panel: A549 cells expressing the dual color reporter construct GFP-mCherry-LC3 and infected with WT Legionella. The number of LC3 vesicles was severely reduced in Legionella-infected cells compared to uninfected control cells. Also, most vesicles present were yellow indicating that the autophagosomes are not acidic (not fused with lysosomes). Lower panel: Mitochondrial morphology and distribution in control and Legionella-infected cells. Legionella infection induces fragmentation and clustering of mitochondria.
Prof. Dr. ivan dikic
Institut für Biochemie II
Ludwig-Maximilians-Universität (LMU) München
60590 Frankfurt a.M.
Office: +49 (0)69 63 01-5652
Prof. Dr. mike heilemann
Institute for Physical and Theoretical Chemistry
60438 Frankfurt a. M.
Office: +49 69 798-29736