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Jörn Dengjel
Christine Gretzmeier
Mostafa Zarei
Sven Eiselein
Andrea Zimmermann
Victoria Küttner
Adrian Sprenger
Rudolf Engelke
Anke Becker
Martin Biniossek
Tilman Brummer
Peter Pfaffelhuber
Enrico Schmidt
Zhike Zi
Roland Nitschke
Andreas Schlosser

Protein Dynamics Group
We study protein dynamics of basic cellular pathways and their deregulation in disease. Next to classical cell and molecular biological approaches our group focuses on protein biochemical assays. Our core competence is quantitative mass spectrometry-based proteomics, which we employ to elucidate cellular signaling events, organellar dynamics, protein turnover and the plasticity of the cellular microenvironment.


Spatiotemporal protein dynamics during autophagy
Funded by a DFG research grant, we investigate time- and stimulus-specific differences of the autophagosomal protein composition by quantitative MS-based proteomics. By performing large scale organellar proteomics experiments, we could elucidate autophagosomal protein dynamics under various conditions, and identified new autophagy-related regulatory proteins. We could shed light on the dynamic character of the autophagosome characterizing influences of different stimuli as well as ample cross-talk between the autophagy- and proteasome-machinery. Currently, we characterize the influence of influenza virus infection on the composition of autophagosomes. By studying protein-protein interactions we aim at characterizing altered molecular pathways during influenza infection.
Next to organellar proteomics approaches we use the analysis of protein turnover, synthesis and degradation to identify new autophagy regulators as well as preferred autophagosomal cargo. We established a new labeling strategy to relatively quantify protein degradation during autophagy. In combination with image analyses, we aim at constructing parameterized cell models in collaboration with Robert F. Murphy, Carnegie Mellon University, to study stimulus-specific differences of macroautophagy, a process still regarded as unspecific.

Global analysis of signal transduction networksWe have established new protocols for efficient and comprehensive analyses of phosphorylation-dependent signal transduction dynamics. Additionally, we started to analyze ubiquitin-dependent signaling events in EGFR signaling. Currently we employ the newly established protocols to follow global signaling events during autophagy. We have recorded signal transduction kinetics of several thousand phosphorylation sites during 30 min of amino acid starvation and rapamycin treatment, respectively. The aim is to identify kinases and phosphatases downstream of mTOR which will allow targeted, mTOR-independent modulation of autophagy.
Next to studying posttranslational modification kinetics, we investigate the influences of oncogenes on cytosolic macromolecular protein complexes. Little is presently known on how the subcellular localization of cytosolic protein complexes relate to tumour progression. In collaboration with T. Brummer, Freiburg University, and R.F. Murphy, we investigate systematically cytosolic macromolecular protein complexes during BRAF- and KRAS-induced oncogenic cell transformation.


Disease proteomics
Funded by a DFG research grant and in collaboration with L. Bruckner-Tuderman, Freiburg University, we investigate disease mechanisms of rare, monogenetic skin disorders. We established proteomics analysis strategies for primary human cells and protocols to study composition changes of extra cellular matrix and secreted proteins (4). As causal genetic mutations for the respective disorders are often known, the work can be regarded as proof of concept to link quantitative proteomics data with gene expression data to identify molecular pathways altered during disease and to design causal, molecular therapies.