German Center for Neurodegenerative Diseases
The DZNE studies causes and mechanisms leading to the formation of neurodegenerative diseases. The aim is, by means of close collaboration between basic, health care and clinical researchers, to rapidly translate knowledge obtained in laboratories into therapeutic applications. Neurodegenerative diseases cannot be cured in most cases, but only treated palliatively. That is why the underlying pathomechanisms shall be elucidated using modern high-throughput technologies at the DZNE. For this purpose, special cell culture tests are applied to identify novel therapeutic targets. At the DZNE, an automated “High Content Screening Facility” with biological safety level S2 and equipped with automated “state-of-the-art” confocal microscopes is available. The special expertise at the DZNE is the development of assays for phenotypic high-content and high-throughput screenings with quantitative multiparametric image analysis. Using this technology, not only single responses in the cell metabolism can be displayed, but complete signal transduction pathways and characteristic cellular phenotypes. Compound libraries as well as siRNA/shRNA technologies can be employed. For the validation of target structures and effectors, the model organisms mouse, C. elegans and Drosophila are available at the DZNE.
Collinet C., Stöter M., Bradshaw C.R., Samusik N., Rink J.C., Kenski D., Habermann B., Buchholz F., Henschel R., Mueller M.S., Nagel W.E., Fava E., Kalaidzidis Y., Zerial M. Systems survey of endocytosis by multiparametric image analysis.Nature. (2010) 464: 243-249
Pelkmans L., Fava E., Grabner H., Hannus M., Habermann B., Krausz E., Zerial M. Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis.Nature. (2005) 436: 78-86.
Vorberg I., Raines A., Story B., Priola S.A. Susceptibility of common fibroblast cell lines to transmissible spongiform encephalopathy agents. J. Infect. Dis. (2004) 189: 431-439.
Krammer, C., Kryndushkin, D., Suhre, M.H., Kremmer, E., Hofmann, A., Pfeifer, A., Scheibel, T., Wickner, R., Schätzl, H.M. and Vorberg, I. From the cover: The Sup35NM domain propagates as a prion in mammalian cells. Proc. Natl. Acad. Sci. (2009) 106: 462-467.
Bach, C., Gilch, S., Greenwood, A., Horsch, M., Facius, A., Schädler, S., Beckers, J., Leib-Mösch, C., Schätzl, H.*, Vorberg, I.* Prion-induced activation of Srebp2-regulated gene expression in neuronal cells. J. Biol. Chem. (2009) 284: 31260-31269 * Corresponding authors.