Research Report 2016 Image Captions Research Report 2016 (covers the period 2014-2016) Cover: are actually induced pluripotent stem cells in a pluripotency test. The cells are Max Delbrück Center for What looks like coral reefs and brightly glowing fishes in this picture Molecular Medicine in the Credit: Gizem Inak (Lab of Erich Wanker, Group of Alessandro Prigione) Helmholtz Association (MDC) stained with a fluorescent dye (Lin28-DAPI). Communications Department Cardiovascular and Metabolic Disease: Robert-Rössle-Str.10 13125 Berlin and lipid droplets white. These fireworks and balloons are fatty Credit:cells. Insulin Vanessa receptors Schmidt (Lab appear of Thomas red andWillnow) early endosomes green. Nuclei are blue Phone: +49-30-9406-0 Email: [email protected] Cancer Research: The colorful confetti of tumor cells which has been stained This Research Report Credit: Matthias Leisegang (formerly Lab of Wolfgang Uckert) is also available online: with different fluorescent dyes. www.mdc-berlin.de Diseases of the Nervous System: Under the microscope the cross-section of Editors mouse skeletal muscle looks has a sponge-like structure. Muscle stem cells stained Vera Glaßer (Editor-in-chief) by an antibody against Pax7 (blue) are located under the basal lamina (green). Jana Schlütter Credit: Dominique Bröhl (formerly Lab of Carmen Birchmeier) Stephanie Sturm BIMSB: Reminiscent of faraway galaxies: cancer cells found in malignant brain Editorial Board tumors produce circular RNA (circRNA), a type of molecule we know relatively Carmen Birchmeier little about. CircRNAs in yellow next to the pink cell bodies with blue nuclei. Norbert Hübner Credit: Christin Stottmeister (Lab of Nikolaus Rajewsky) Friedrich C. Luft Nikolaus Rajewsky ECRC: This image depicts human myoblasts and myotubes derived from a biopsy. Claus Scheidereit Myosin heavy chain (MyHC) protein of fused muscle cells is stained with a green Book Design Credit: Eric Metzler, PhD student (Lab of Simone Spuler) unicom-berlin.de fluorescent dye; nuclei appear in blue. Technology Platforms: The 3-D-mouse embryo is a reconstruction made up of Printing 360 individual images, the developing nervous system appears in orange. Laserline, Berlin 2017 Credit: Julian Heuberger (Lab of Walter Birchmeier), Anje Sporbert (Advanced Light Microscopy (ALM) technology platform) Research Report 2016 Table of Contents II Table of Contents VIII Introduction by the Scientific Director Prof. Dr. Martin Lohse XI The MDC 1 Cardiovascular and Metabolic Disease Coordinator: Norbert Hübner 4 Molecular Biology of Peptide Hormones Michael Bader 8 Mathematical Cell Physiology Martin Falcke 10 Integrative Vascular Biology Laboratory Holger Gerhardt 14 Neuromuscular and Cardiovascular Cell Biology Michael Gotthardt 18 Genetics and Genomics of Cardiovascular Diseases Norbert Hübner 22 Mobile DNA Zsuzsanna Izsvák 26 Anchored Signalling Enno Klußmann 28 Molecular genetics of chronic inflammation and allergic disease Young-Ae Lee 32 Receptor signalling Martin Lohse 36 Hypertension Genetics, Regulators, and Environment Friedrich Luft 40 Molecular Muscle Physiology Ingo Morano 44 Ultrahigh Field Magnetic Resonance (UHF-MR) Thoralf Niendorf 48 Electrochemical signaling in development and disease Daniela Panáková 50 Molecular Epidemiology Tobias Pischon 54 microRNA and Molecular Mechanisms of Metabolic Diseases Matthew Poy 56 Molecular and Translational Kidney Research Kai Schmidt-Ott 58 Proteome Dynamics Matthias Selbach 62 Molecular and Cellular Basis of Embryonic Development Francesca M. Spagnoli 64 Genetics of Metabolic and Reproductive Disorders Mathias Treier 68 Molecular Cardiovascular Research Thomas Willnow II MDC Research Report 2016 TABLE OF CONTENTS Table of Contents 73 Cancer Research Coordinator: Claus Scheidereit 76 Signal Transduction in Development and Cancer Walter Birchmeier 80 Molecular Immunology and Gene Therapy Thomas Blankenstein 84 Structure, function and mechanism of membrane-associated GTPases Oliver Daumke 88 DNA Repair and Maintenance of Genome Stability Michela Di Virgilio 90 Molecular Oncology Gaetano Gargiulo 92 Macromolecular Structure and Interaction Udo Heinemann 96 Microenvironmental Regulation in Autoimmunity and Cancer Uta E. Höpken 98 IPS cell based disease modelling Ralf Kühn 100 Cell Differentiation and Tumorigenesis Achim Leutz 104 Molecular Immunotherapy Antonio Pezzutto 106 Immune Regulation and Cancer Klaus Rajewsky 110 Translational Tumorimmunology Armin Rehm 112 Spatio-temporal control of Rho GTPase signaling Oliver Rocks 114 Signal Transduction in Tumor Cells and Development Claus Scheidereit 118 Cancer Genetics and Cellular Stress Responses in pathogenesis and treatment of lymphatic malignancies Clemens A. Schmitt 120 Stem cell and macrophage biology Michael Sieweke 122 Intracellular Proteolysis Thomas Sommer 126 Molecular Cell Biology and Gene Therapy Wolfgang Uckert 128 Mathematical Modelling of Cellular Processes Jana Wolf MDC Research Report 2016 III TABLE OF CONTENTS 131 Diseases of the Nervous System Coordinator: Carmen Birchmeier-Kohler 134 Developmental Biology / Signal Transduction Carmen Birchmeier-Kohler 138 Research Focus Mina Gouti 140 Molecular Pathways in Cortical Development Annette Hammes 142 Physiology and Pathology of Ion Transport Thomas Jentsch 146 Cellular Neurosciences Helmut Kettenmann 150 Molecular Physiology of Somatic Sensation Gary Lewin 154 Neural Circuits and Behaviour James Poulet 156 Mitochondria and cell fate reprogramming Alessandro Prigione 158 Developmental Neurobiology Fritz G. Rathjen 162 Role of GPRIN1 on kainate-receptors function Dietmar Schmitz 164 Proteomics and Molecular Mechanisms of Neurodegenerative Diseases Erich Wanker 168 Development and Function of Neural Circuits Niccolò Zampieri 171 Berlin Institute for Medical Systems Biology Nikolaus Rajewsky 174 BIMSB Bioinformatics / Mathematical Modelling Altuna Akalin 176 Non-coding RNAs and mechanisms of cytoplasmic gene regulation Marina Chekulaeva 178 Quantitative developmental biology Jan Philipp Junker 180 Dynamics and functions of the enhancer landscape during zebrafish development and cardiogenesis Scott Lacadie 182 RNA Biology and Posttranscriptional Regulation Markus Landthaler 184 RNA Structure and Transcriptome Regulation Irmtraud M. Meyer 188 Evolutionary Modeling and Inference in Computational Systems Biology Benedikt Obermayer IV MDC Research Report 2016 TABLE OF CONTENTS 190 Computational Regulatory Genomics Uwe Ohler 194 Epigenetic regulation and chromatin architecture Ana Pombo 198 Microscopy, Image Analysis & Modeling of Developing Organisms Stephan Preibisch 200 Systems Biology of Gene Regulatory Elements Nikolaus Rajewsky 204 Evolutionary and Cancer Genomics Roland Schwarz 206 Gene regulation and cell fate decision in C. elegans Baris Tursun 208 Systems biology of neural tissue differentiation Robert P. Zinzen 211 The Experimental and Clinical Research Center (ECRC) Friedrich C. Luft 216 Hypertension-induced Target-Organ Damage Dominik N. Müller Ralf Dechend 218 Blood Vessel Function and Target-Organ Damage / Registry Diabetic Nephropathy Maik Gollasch 220 Nephrology and Inflammatory Vascular Diseases Ralph Kettritz 222 Biology of Malignant Lymphomas Stephan Mathas Martin Janz 224 Outpatient Clinic for Neuroimmunology Friedemann Paul 226 Cardiac MRI Jeanette Schulz-Menger 228 Muscle Research Unit and Out-patient Clinic for Muscle Diseases Simone Spuler 230 Translational Oncology of Solid Tumors Ulrike Stein MDC Research Report 2016 V TABLE OF CONTENTS 233 Scientific Infrastructures & Technology Platforms Jutta Steinkötter 236 Advanced Light Microscopy Anje Sporbert 238 Biobank Tobias Pischon 240 Bioinformatics Platform, BIMSB Altuna Akalin 242 Chemical Biology Platform Jens Peter von Kries Marc Nazaré 244 Electron Microscopy Bettina Purfürst 246 Genomics, BIMSB Sascha Sauer 248 Magnetic Resonance (B.U.F.F.) Thoralf Niendorf 250 Metabolomics, BIH Platform at MDC Jennifer Kirwan 252 Light Microscopy Platform, BIMSB Andrew Woehler 254 Pathophysiology Arnd Heuser 256 Pluripotent Stem Cells Sebastian Diecke 258 Preparative Flowcytometry Hans-Peter Rahn 260 Proteomics Currently N.N. 262 Proteomics / Metabolomics, BIMSB Stefan Kempa 264 Transgenic Core Facility Ralf Kühn VI MDC Research Report 2016 TABLE OF CONTENTS 267 Annex 268 Appointments and Recruitments 272 European Research Council (ERC) Grants 274 Awards 276 Selected Highlight Publications 278 Scientific Meetings and Conferences 280 Selected Seminars 2014 – 2016 284 Facts and Figures 286 Organizational Structure 290 Index MDC Research Report 2016 VII Introduction by the Scientific Director Prof. Dr. Martin Lohse Life in our labs deals with fundamental Within this program, we will concentrate questions of health and disease, while at - the same time focusing on small details – tives on system-wide diseases, namely: such as the intricate workings of an organ- •on cardiovascular five topics that disease reflect anddifferent metabolism, perspec ism, a cell and even an ion channel or recep- which inherently affect the whole orga- seem abstract. However, medicine cannot • developmental biology, which includes advancetor. At first without sight, uncovering such basic theresearch basic promay- anism; better understanding of inherited dis- cesses that underlie life. orders and how diseases may have their roots early in life, and furthers regenera- Exploring these mechanisms and transla- • clinical applications has been our mission aretive keymedicine; players in the pathogenesis of fromting our