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Structure of the Group Group Leader Dr. Gerd Wallukat Scientists Dr. Sabine Bartel Dr. Wolfgang Schulze Dr. Ludmila Okrulikova* Graduate and Undergraduate Students Janette Freier Qin Fu* Marion Janczikowski Gilka Muñoz Saravia* Technical Assistants Karin Karczewski Christian Wolf Secretariat Dana Lafuente* * part of the period reported remodelling of pulmonary vessels. The tonus increase is associated with a right ventricular hypertension of the myocard. The ETA antibodies appear in combination with an antibody against the alpha1- adrenoceptor in this disease. In both cases the natural agonists against these receptors induce vasoconstriction. Therefore, we assumed that the agonistic antibodies my be involved in the pathogenesis of pulmonary hypertension. Selected Publications Okrulicova, L, Morwinski, R, Schulze, W, Bartel, S, Weismann, P, Tribulova, N, Wallukat, G. (2007). Autoantibodies against G- protein coupled receptors modulate heart mast cells. Cell. Mol. Immunol. 4, 127-33. Hubel, CA, Wallukat, G, Wolf, M, Herse, F, Rajakumar, A, Roberts, JM, Markovic, N, Thadhani, R, Luft, FC, Dechend, R. (2007). Agonistic angiotensin II type 1 receptor antibodies in postpartum women with a history of preeclampsia. Hypertension 49, 612-7. Christ, T, Schindelhauer, S, Wettwer, E, Wallukat, G, Ravens, U. (2006). Interaction between autoantibodies against the beta1- adrenoceptor and isoprenaline in enhancing L-type Ca ++ current in rat ventricular myocytes. J. Mol. Cell. Cardiol. 41, 716-23. Dragun,D, Müller,DN, Bräsen, JH, Fritsche, L, Nieminen-Kelhä, M, Dechend, R, Kutscher, U, Rudolph, B, Hoebeke, J, Eckert, D, Mezah, I, Plehm, R, Schönemann, L, Unger, T, Budde, K, Neumayer, HH, Luft, FC, Wallukat, G. (2005). Angiotensin II type1-receptor activating antibodies in renal-allograft rejection. N. Engl. J. Med. 352, 558-69. Peter, JC, Wallukat, G, Tugler, J, Maurice, D, Roegel, JC, Briand, JP, Hoebeke, J. (2004). Modulation of the M2 muscarinic acetylcholine receptor activity with monoclonal ant-M2 receptor antibody fragments. J. Biol. Chem. 279, 55679-706. Patents/ Licences MDC 0514 EP, AKZ 060757 594.9 Title: Peptides against autoantibodies associated with glaucoma and use of these peptides MDC 0210 AKZ. PCT/DE03/03988 Title: Bestimmung agonistischer Autoantikörper MDC 0704 EP, AKZ 07090115.2 Title: Autoantikörper gegen den Endothelin1-ETA Rezeptor MDC 0704 US Appl.No. 60/493,697 Title: Autoantibodies binding peptides and their use fort he treatment of vascular diseases. MDC 0302 AKZ. 103 11 106.9 Title: Peptide gegen Kälteunverträglichkeit hervorrufende Autoantikörper und ihre Verwendung. 50 Cardiovascular and Metabolic Disease Research
Genetics, Genomics, Bioinformatics, and Metabolism Coordinator: Nikolaus Rajewsky Systems Biology of Gene Regulatory Elements Nikolaus Rajewsky My lab uses computational and experimental methods to dissect, systems-wide, function and evolution of gene regulation in metazoans. One major focus is to understand more about gene regulation by small RNAs, in particular microRNAs. We are developing predictive models for the targets of microRNAs. To probe general mechanisms of gene regulation of microRNAs, we work in cell lines. We are also investigating the function of small RNAs during very early development of C. elegans. Furthermore, we have established planaria as a model system in our lab. These freshwater flatworms are famous for their almost unlimited ability to regenerate any tissue via pluripotent, adult stem cells. We are studying the role of small RNAs in planarian regeneration. Introduction A major lesson from recent genomics is that metazoans share to a large degree the same repertoire of proteinencoding genes. It is thought that differences between cells within a species, between species, or between healthy and diseased animals are in many cases due to differences in when, where and how genes are turned on or off. Gene regulatory information is to a large degree hardwired into the non-coding parts of the genome. Our lab focuses on decoding transcriptional regulation (identification and characterization of targets of transcription factors in non-coding DNA) and post-transcriptional control mediated by a class of small, non-coding RNAs (microRNAs). microRNAs are a recently discovered large class of regulatory genes, present in virtually all metazoans. They have been shown to bind to specific cis-regulatory sites in 3’ untranslated regions (3’ UTRs) of protein-encoding mRNAs and, by unknown mechanisms, to repress protein production of their target mRNAs. Our understanding of the biological function of animal microRNAs is just beginning to emerge, but it is clear that microRNAs are regulating or involved in a large variety of biological processes and human diseases, such as developmental timing, long-term memory, signalling, homeostasis of key metabolic gene products such as cholesterol, apoptosis, onset of cancer, Tourette’s syndrome, and others. Systems Biology of Gene Regulation Catherine Adamidi, Kevin Chen, Teresa Colombo, Minnie Fang, Marc Friedlaender, Signe Knespel, Azra Krek, Andreas Kuntzagk, Svetlana Lebedeva, Tatjana Luganskaja, Jonas Maaskola, Marlon Stoeckius, Nadine Thierfelder) It is clear that a better understanding of gene regulation and in particular of the just emerging universe of non-coding RNAs can only come by integrating various data sources (comparative sequence analysis, mRNA expression data, protein-protein interactions, mutant phenotypes from RNAi screens, polymorphism data, experimentally defined gene regulatory networks, ChIP-chip data, etc) since each data source alone is only a partial description of how cells function. For example, to understand microRNA function, we not only need to identify their targets but also to decode how microRNAs are transcriptionally regulated. A major focus of the lab is therefore in developing methods that integrate different data sources and methods to produce global and yet specific predictions about how, when, and where gene are regulated. This will ultimately lead to the identification and functional description of gene regulatory networks. We will continue to test, develop and “translate” these methods and their predictions using specific biological systems, such Cardiovascular and Metabolic Disease Research 51
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Research Report 2008 MDC Berlin-Buc
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Research Report 2008 (covers the pe
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Cell Polarity and Epithelial Morpho
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Molecular Cell Biology and Gene The
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Foreword Vorwort As this book was b
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which survey the quality of protein
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Control of DNA Replication Manfred
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Structural and Functional Genomics
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Structure and Membrane Interaction
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Tumor Immunology Coordinator: Marti
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Formation of segregated ectopic fol
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What are the physiological features
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Visualization of the UniHi interact
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Dagmar Ehrnhöfer* Manuela Jacob* M
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Lack of axonal bifurcation within t
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Molecular Physiology of Somatic Sen
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Mitochondrial Dynamics Christiane A
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Neuronal Stem Cells Gerd Kempermann
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Targeting Ion Channel Function Ines
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Molecular Neurology Frauke Zipp T h
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Academics Akademische Aktivitäten
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2007 19. January Neujahrsempfang de
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Overview Überblick
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erzielen, brauchen wir neue gemeins
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The Clinical Research Center (CRC)
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y such scientists in conjunction wi
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Zudem bietet das ECRC-Modell eine h
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(Photo: David Ausserhofer/ Copyrigh
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Business School” addressed challe
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Prof. Dr. Gary R. Lewin MDC Berlin-
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Dr. Thomas Müller Prof. Dr. Claus
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Type of Financing/Art der Finanzier
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Collaborative Research Centres (SFB
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MDC MAX-DELBRÜCK-CENTRUM FÜR MOLE
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Campus Map Campusplan Robert-Rössl
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How to find your way to the MDC Der
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