Document Actions
FRIAS - Jörn Dengjel
Dr. Joern Dengjel
| ||
Joern Dengjel is a group leader at the Center for Biological Systems Analysis at the University of Freiburg. His research focuses on the description of spatio-temporal protein dynamics during autophagy, a cellular degradation pathway.
Joern Dengjel studied Biochemistry in Potsdam and Tuebingen, where he also completed his doctoral thesis in February 2005 at the Department of Immunology, Institute for Cell Biology. After one year at Immatics Biotechnologies, Tuebingen, working as a senior scientist in the Tumor Analytics group, he started a Postdoc at the Center of Experimental BioInformatics, University of Southern Denmark, Odense. For three years he worked on spatio-temporal protein dynamics using functional proteomics approaches. Since December 2008 he is heading a research group at the Center for Biological Systems Analysis, Freiburg.
He received several fellowships during his studies, such as a doctoral scholarship of the German Merit Foundation and an EMBO long-term fellowship.
- Kristensen, A.R., Gade, S., Hoyer-Hansen, M., Jaattela, M., Dengjel, J.*, Andersen, J.S.*, Ordered organelle degradation during starvation-induced autophagy, Mol Cell Proteomics, 2008, in press
- Wahlström,J., Dengjel,J., Persson,B., Duyar,H., Rammensee,H.G., Stevanovic,S., Eklund,A., Weissert,R., and Grunewald,J., Identification of HLA-DR–bound peptides presented by human bronchoalveolar lavage cells in sarcoidosis. J Clin Invest. 2007, 117:3576-82
- Dengjel,J.*, Akimov,V.*, Olsen,J.V., Bunkenborg,J., Mann,M., Blagoev,B., and Andersen,J.S., Quantitative proteomic assessment of very early cellular signaling events. Nat Biotechnol. 2007, 25:566-8.
- Dengjel,J.*, Nastke,M.D.*, Gouttefangeas,C., Gitsioudis,G., Schoor,O., Altenberend,F., Muller,M., Kramer,B., Missiou,A., Sauter,M., Hennenlotter,J., Wernet,D., Stenzl,A., Rammensee,H.G., Klingel,K., and Stevanovic,S., Unexpected abundance of HLA class II presented peptides in primary renal cell carcinomas. Clin Cancer Res. 2006, 12:4163-70
- Dengjel,J.*, Schoor,O.*, Fischer,R., Reich,M., Kraus,M., Müller,M., Kreymborg,K., Altenberend,F., Brandenburg,J., Kalbacher,H., Brock,R., Driessen,C., Rammensee,H.G., and Stevanovic,S., Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. PNAS, 2005, 102:7922-7
- Dengjel,J.*, Decker,P.*, Schoor,O., Altenberend,F., Weinschenk,T., Rammensee,H.G., and Stevanovic,S., Identification of a naturally processed cyclin D1 T-helper epitope by a novel combination of HLA class II targeting and differential mass spectrometry. Eur.J.Immunol. 2004, 34: 3644-51
* Authors contributed equally to this work.
Spatio-temporal protein dynamics during autophagy
Background
Autophagy is an evolutionary conserved process wherein catabolism of cytoplasm generates energy which allows cell survival under condition of reduced nutrient availability. It is thought to be important for the turn-over of whole organelles and long-lived proteins. However, prolonged autophagy can lead to type II programmed cell death. Manny aspects of autophagy regulation are still not fully understood. The best-characterized inhibitory pathway includes a class I PI3K and mTOR. On the other hand, a class III PI3K is needed for autophagy activation. Autophagy has been linked to several diseases amongst others cancer and neurodegenerative diseases. We are following several projects concerning the characterization of autophagy using a combination of techniques including quantitative mass spectrometry (MS)-based proteomics, confocal-imaging, and RNA interference (RNAi)-based screens. Currently, we are characterizing the autophagosome, the double-membrane bound vacuole containing cytoplasmic material destined for degradation, with the aim to identify human proteins related to autophagy. We are also interested in global protein dynamics during long-term starvation to characterize the influence of different types of autophagy, macroautophagy and chaperone-mediated autophagy (CMA), on the cellular proteome. Last but not least, we are using a quantitative phosphoproteomics approach to compare signaling events involved in autophagy and in type I programmed cell death pathways (apoptosis). Although the two processes are morphologically distinct, they are both characterized by lack of tissue inflammatory responses and may share signaling pathways.
Methods
To reveal new components in the analyzed organelle and signaling networks we are using MS-based proteomics in combination with stable isotope labelling by amino acids in cell culture (SILAC). SILAC is a quantitative proteomic strategy that metabolically labels the entire proteome, thus, making it distinguishable by MS analysis. Different populations of cells can be grown in medium containing distinct forms of arginine (Arg) and lysine (Lys). Subsequently, cell populations can be mixed and analyzed in one MS experiment. This allows the quantitation of proteins from different cellular states. Depending on the setup we are able to describe an organellar proteome or to follow site-specific phosphorylation changes in signaling pathways over a certain timeframe. The newest mass spectrometers allow specific screening for phosphopeptides on a routine basis. As sensitivity is down to the subfemtomolar range it is now possible to perform systemic analyses on as few as 107 cells.
