Stimulus- and time-dependent protein dynamics of the autophagosome analyzed by quantitative mass spectrometry

• Applicant: Professor Dr. Jörn Dengjel
• Subject Area: Biochemistry
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 180712627

We are investigating time- and stimulus-specific differences of the autophagosomal protein composition by quantitative mass spectrometry-based proteomics. Our work will yield new insights into a basic cellular degradation pathway whose deregulation is involved in numerous diseases, inter alia in cancer development and bacterial and viral immune evasion. Thus, we expect that the described molecular networks will allow the design of new therapeutic strategies in diverse disease settings. The autophagosomal/lysosomal system is next to the ubiquitin/proteasome system responsible for the majority of cellular proteolysis. The autophagosome encloses cytosol and organelles targeting them for degradation by lysosomal fusion yielding free amino acids. Autophagy has been regarded as an unspecific bulk degradation pathway. However, lately more and more specific autophagy subtypes are being described and it is still largely unknown which bio-molecules are present under which conditions and to which time point in the autophagosome. We will address these questions by inducing autophagy by different stimuli and analyzing autophagosomes at different time points. In addition, we are investigating the influence of viral infections on autophagosomal composition and the influence of autophagy in viral immune evasion.

• DFG Programme: Research Grants