Max Delbrück Center for Molecular Medicine
The research focus of the MDC is the elucidation of molecular causes of diseases with the aim of translating these findings into clinical application. One important goal is to identify new targets for therapeutic approaches and their characterisation down to the atomic level by X-ray structure analysis. A most relevant resource for the scientific work at MDC is the use of animal models. More than 1000 transgenic mice of which more than half of them were generated at MDC and about 100 different rat strains all made by the MDC are available. Additionally, also small animal models are established such as zebrafish, xenopus frog, drosophila flies, C. elegans worm and yeast.
MDC offers access to cell lines fervid from these animal models for compound screening. Long term animal studies will be available at the planned in vivo patho-physiology lab (IPL).
For its drug research, the MDC cooperates with the neighbouring screening platform at the FMP. This has permitted the identification of, for instance, first hits for chemokine receptor antagonists for a therapeutic strategy for chronic inflammatory autoimmune diseases; new approaches to the treatment of disorders of serotonin metabolism (which causes a variety of psychiatric disorders such as depression); or inhibitors of specific protein tyrosine phosphatases to inhibit cell migration and the metastasis of tumours. Drug research has also been carried out with great success in the field of protein aggregation-induced neurodegenerative diseases.
Leibniz-Institut für Molekulare Pharmakologie
The FMP is dedicated to Molecular Pharmacology which, by definition, investigates the mechanisms underlying the responses of biological systems to challenges by exogenous substances. The research activities are structured around three areas which are of prime importance for its mission: Chemical Biology, Structural Biology, and Signal Transduction/Molecular Genetics. The Chemical Biology section contributes expertise in the discovery, design, synthesis, and characterisation of biologically active molecules. Its Chemical Biology platform is currently composed of six modules: Drug Design /Computational Chemistry, Compound Management with an automated storage system for 200.000 compounds, Process Automation, HTS operating four independent screening robots with a large panel of signal detection devices, Synthetic Chemistry with three chemistry teams, and Cheminformatics. The platform provides access to a unique compound collection (currently 65.000) from commercial as well as proprietary samples and since 2004 served as a central technology platform for more than 150 projects in the frame work of academic and private research programs and the German ChemBioNet. This platform is also the initiator and core of EU-OPENSCREEN, a European research infrastructure initiative on the ESFRI roadmap.
Merkert S, Schubert M, Olmer R, et al. High-Throughput Screening for Modulators of CFTR Activity Based on Genetically Engineered Cystic Fibrosis Disease-Specific iPSCs. Stem Cell Reports. 2019;12(6):1389‐1403. doi:10.1016/j.stemcr.2019.04.014
Bieschke, J., Russ, J., Friedrich, R.P., Ehrnhoefer, D.E., Wobst, H., Neugebauer, K., Wanker E.E. EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity.Proc. Natl. Acad. Sci. USA (2010) 107: 7710-7715.
Jehle S., Rajagopal P., Bardiaux B., Markovic S., Kühne R., Stout J.R., Higman V.A., Klevit R.E., van Rossum B.J., Oschkinat H. Solid-state NMR and SAXS studies provide a structural basis for the activation of αBcrystallin oligomers.Nat. Struct. Mol. Biol. (2010) 17: 1037-1042
Weinert S., Jabs S., Supanchart C., Schweizer M., Gimber N., Richter M., Rademann J., Stauber T., Kornak U., Jentsch T.J. Lysosomal Pathology and Osteopetrosis upon loss of H+‐driven Lysosomal Cl-Accumulation.Science. (2010) 328: 1401-1403
Ahsanullah, Schmieder P., Kühne R., Rademann, J. Metal-free, regioselective triazole ligations deliver locked cis-peptide mimetics.Angew. Chem. Int. Ed. (2009) 48: 5042-5045
Podust L.M., Quellet H., von Kries J.P., de Montellano P.R. Interaction of Mycobacterium tuberculosis CYP130 with heterocyclic arylamines.J. Biol. Chem. (2009) 284: 25211-25219
Dickhaut K., Hoepner S., Eckhard J., Wiesmueller K.H., Schindler L., Jung G., Falk K., Roetzschke O. Enhancement of tumour-specific immune responses in vivo by 'MHC loading-enhancer' (MLE).PLoS One (2009) 4: e6811.
Hellmuth K., Grosskopf S., Lum C.T., Würtele M., Röder N., von Kries J.P., Rosario M., Rademann J., Birchmeier W. Specific Inhibitors of the Protein Tyrosine Phosphatase Shp2 Identified by High-throughput Docking.Proc. Natl. Acad. Sci. USA. (2008) 105: 7275-7280
Ehrnhoefer, D.E., Bieschke, J., Boeddrich, A., Herbst, M., Masino, L., Lurz, R., Engemann, S., Pastore, A., Wanker, E.E. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers.Nat. Struct. Mol. Biol. (2008) 15: 558-566.
Hellmuth K., Grosskopf S., Lum C.T., Würtele M., Röder N., von Kries J.P., Rosario M., Rademann J. and Birchmeier W. Specific Inhibitors of the Protein Tyrosine Phosphatase Shp2 Identified by High-throughput Docking.Proc. Natl. Acad. Sci. USA (2008) 105: 7275-7280.
Lygren B., Carlson C.R., Santamaria K., Lissandron V., McSorley T., Litzenberg J., Lorenz D., Wiesner B., Rosenthal W., Zaccolo M., Taskén K., Klussmann E. AKAP complex regulates Ca2+ re-uptake into heart sarcoplasmic reticulum.EMBO Rep. (2007) 8:1061-1067.