"Autophagy is an essential process that enables cells to engulf and digest portions of their cytoplasm, thereby accomplishing quality and quantity control of organelles, proteins and pathogens. These homeostatic and adaptive function intricately link autophagy to diverse health and disease states including innate immunity. Microbial pathogens that successfully parasitize eukaryotic cells have evolved to evade autophagic microbial defenses (xenophagy) and subvert the host autophagic responses for their own survival and/or growth. Central to xenophagy is cargo recognition and dynamic rearrangements of membrane-bound compartments to sequester and deliver pathogen load for lysosomal degradation. Microbial adaptation strategies identified to date have targeted both of these crucial and intertwining functions. However, the precise molecular mechanisms underpinning pathogen avoidance of host-cell autophagy and immune responses are only poorly understood. This raised specific questions about host-pathogen interactions: (1) What is the dynamic response of the core autophagy system to bacterial pathogens? (2) How does the autophagy pathway impinge on the endocytic system and how do pathogens subvert intracellular vesicle trafficking systems? (3) What is the molecular machinery involved in detecting cargo and how do pathogens counter this response? This proposal seeks to elucidate pathways and functions involved in xenophagy and to identify mechanisms by which pathogens usurpate the anti-bacterial cell-autonomous defence system. To address these questions, we will employ a highly complementary multidisciplinary platform, which combines biochemical, cell and infection biological approaches with emerging proteomics and high-content imaging techniques. Together, this proposal has the potential to uncover novel molecular mechanisms that define the signaling machinery driving xenophagy of pathogens, thereby contributing to advancements in the fields of cell and infection biology."
Field of science
- /medical and health sciences/health sciences/public and environmental health/epidemics prevention/immunisation
- /natural sciences/biological sciences/microbiology/bacteriology
Call for proposal
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Funding SchemeERC-SG - ERC Starting Grant
60323 Frankfurt Am Main