Proteomics, Cell Biology, Biochemistry (Behrends)

Project description

Classically viewed as a lysosomal degradation process, emerging evidence implicates autophagy in secretion, including unconventional secretion of proteins lacking signal peptides, extracellular vesicle production, and conventional secretion of inflammatory cytokines. These processes, collectively termed secretory autophagy, broaden our fundamental understanding of the autophagy pathway in non-cell autonomous control of cell fate decisions and tissue microenvironments in healthy and disease states. Despite a proposed role of LC3/GABARAP our understanding of secretory autophagy remains rudimentary. This project will combine highly complementary proteomics and imaging methods to decipher the repertoire of proteins secreted via autophagy, dissect the underlying mechanisms of autophagy-dependent secretion and decode the functional importance of secretory autophagy in microglia. The student will employ (i) proximity labeling of secreted LC3/GABARAP proteins, (ii) secretome analyses of LC3/GABARAP knockout cells, (iii) MS of immune isolated secretory autophagy carriers and (iv) integrative bioinformatics to systematically identify cargo of secretory autophagy. Upon their validation with cell biological methods, the student will employ cargo proteins in biochemical binding studies and reconstitution experiments. The results from our efforts will provide invaluable insights into autophagy processes intertwined with other essential intra- and intercellular processes and will also be of critical importance for validating targets for therapeutic intervention.