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Research Report RESEARCH REPORT LEIBNIZ FORSCHUNGSINSTITUT FÜR MOLEKULARE PHARMAKOLOGIE PROF. DR. KARL-HEINZ ALTMANN SCIENTIFIC ETH Zürich, Zürich, Schweiz, 2012 – 2019 PROF. DR. NILS BROSE (Chair 2013 – 2019) ADVISORY BOARD Max-Planck-Institut für Experimentelle Medizin, Göttingen, 2012 – 2019 PROF. DR. ULRIKE EGGERT King’s College London, London, Vereinigtes Königreich, 2013 – 2020 DR. MATTHIAS GOTTWALD Bayer Pharma AG, Berlin, 2016 – 2019 PROF. DR. THOMAS GUDERMANN Ludwig-Maximilians-Universität München, München, 2013 – 2020 PROF. DR. ECKART GUNDELFINGER Leibniz-Institut für Neurobiologie, Magdeburg, 2013 – 2020 PROF. DR. THOMAS LANGER Max-Planck-Institut für Biologie des Alterns, Köln, 2020 – 2023 PROF. DR. BEAT MEIER ETH Zürich, Zürich, Schweiz, 2013 – 2020 DR. FRANZ VON NUSSBAUM Innovation Campus Berlin, NUVISAN ICB GmbH, Berlin, 2020 – 2023 PROF. DR. STEFAN OFFERMANNS (Chair since 2020) Max-Planck-Institut für Herz- und Lungenforschung, Bad Nauheim, 2016 – 2023 PROF. DR. STEFAN RAUNSER Max-Planck-Institut für Molekulare Physiologie, Dortmund, 2017 – 2020 PROF. DR. MICHAEL SATTLER Deutsches Forschungszentrum für Gesundheit und Umwelt (DFGU), Helmholtz-Zentrum München, Neuherberg, 2020 – 2023 PROF. DR. PETRA SCHWILLE Max-Planck-Institut für Biochemie, Martinsried, 2012 – 2019 PROF. DR. REBECCA WADE ZMBH, Universität Heidelberg und HITS gGmhH Heidelberger Institut für Theoretische Studien, Heidelberg, 2013 – 2020 PROF. DR. HELMA WENNEMERS ETH Zürich, Zürich, Schweiz, 2020 – 2023 2 MOLECULAR PHYSIOLOGY AND CELL BIOLOGY RESEARCH REPORT 2019/2020 RESEARCH REPORT 2019/2020 In 2019/2020, our researchers published 218 articles, including 191 peer-reviewed articles in scientific journals. A number of these articles are presented as highlights throughout the report. In den Jahren 2019/2020 veröffentlichten unsere Forschenden 218 Publikationen, darunter 191 referierte Beiträge in Fachzeitschriften. Einige von ihnen werden in diesem Bericht auf Highlight-Seiten vorgestellt. CONTENT 02 CONTENT RESEARCH REPORT 2019/2020 → STRUCTURAL BIOLOGY 32 Adam Lange Molecular Biophysics 36 Hartmut Oschkinat NMR-Supported Structural Biology 38 Leif Schröder Molecular Imaging 42 Fan Liu Structural Interactomics 44 Ronald Kühne Computational Chemistry / Drug Design 46 Gerd Krause FOREWORD 04 Structural Bioinformatics and Protein Design 50 AWARDS 08 Peter Schmieder NMR 52 → MOLECULAR PHYSIOLOGY & CELL BIOLOGY 10 → CHEMICAL BIOLOGY 56 Thomas J. Jentsch Christian P.R. Hackenberger Physiology and Pathology of Ion Transport 12 Chemical Biology II 58 Volker Haucke Dorothea Fiedler Molecular Pharmacology and Cell Biology 14 Chemical Biology I 60 Andrew J.R. Plested Marc Nazaré Molecular Neuroscience and Biophysics 16 Medicinal Chemistry 64 Alexander Matthias Walter Jens Peter von Kries Molecular and Theoretical Neurosciences 20 Screening Unit 66 Tanja Maritzen NEW GROUPS AT THE FMP 70 Membrane Traffic and Cell Motility 22 ALL RESEARCH GROUPS 73 Janine Kirstein Proteostasis in Aging and Disease 24 FACTS AND FIGURES 74 Martin Lehmann / Dmytro Puchkov TECHNOLOGY TRANSFER 76 Cellular Imaging 28 VISUALIZING SCIENCE 77 Natali Kristina Wisbrun Animal Facility 30 PUBLIC RELATIONS 78 EDUCATION AND TRAINING 80 ADMINISTRATIVE AND TECHNICAL SERVICES 82 IMPRINT 85 FORSCHUNGSBERICHT 2019/2020 INHALT 03 reporting period. By using innovative genetic, chemical biological and structural biological methods such as cryo-electron microscopy, they seek to explore the causes of neurological disor- ders and of colorectal cancer in a bid to develop new options for the diagnosis and treatment of these diseases. In turn, junior group leaders Tanja Maritzen and Janine Kirstein have left the Institute to take up professorships at the universities of Kaiserslautern and Bremen, respectively. In this way, the FMP contributes visibly to Germany’s role as a science location by acting as a breeding ground for successful early-stage researchers. We would also like to take this opportunity to thank Ronald Kühne and Gerd Krause, group leaders who helped shape and determine research at the DEAR READERS, DEAR FMP and who have now retired. FRIENDS OF THE FMP, Successful research has also led to the founding of the spin-off companies Tubulis and ProSion, which take innovative chemical biological and LIEBE LESER*INNEN, synthetic approaches to disease control. Both companies are a testament to the successful LIEBE FREUND*INNEN translational research conducted at the FMP and at the Campus Berlin-Buch. DES FMP, In addition to these examples of successful enterprise creation, we have also enhanced our role as a partner of Berlin’s universities in the → In the almost three decades since its foundation, last two years. For example, Fan Liu, leader of the the Leibniz-Forschungsinstitut für Molekulare Structural Interactomics research group, was Pharmakologie (FMP) has established itself as one additionally appointed as Professor for Structural of the world’s most outstanding research centers Interactomics at Charité – Universitätsmedizin in in molecular pharmacology. Unlike most medical 2020; a joint professorship in Structural Chemical institutions, which conduct disease- based or Biology with Technische Universität Berlin is now indication-based pharmacological research, the reaching the final appointment stage. These FMP takes an interdisciplinary approach to examples illustrate how closely the FMP is linked molecular pharmacology. This approach involves to Berlin’s universities, and to the non-university researchers from structural biology working institutions that have teamed up to form the together with scientists from the fields of genetics, BR50 alliance, to which the FMP also belongs. physics, chemical biology or cell biology. The aim of this interdisciplinary mode of research is to An important development in the reporting develop novel approaches to molecular diagnos- period is the further expansion of EU-OPEN- tics and therapy, helping us create the medicine SCREEN – a European high-capacity screening of tomorrow. network initiated by the FMP located on Campus Berlin-Buch – and its partner sites at the FMP. As Our research must constantly evolve to remain such, Campus Berlin-Buch has established itself at the forefront of science. This applies not only as the European gateway for drug screening to the development or establishment of new research. technologies, such as CRISPR-based genome engineering or innovative methods of structural Last but not least, FMP scientists once again biology, but also to the biological topics and scooped numerous awards and prizes for their systems under study. As a result of our efforts to successful work in 2019/2020, which we see as foster change, we have recruited Noa Lipstein, a great honor and an incentive to keep up the Daniel Roderer and Johannes Broichhagen as great work. Turn the page to read more about new junior group leaders during the 2019/2020 our research and how the resulting insights 04 FOREWORD RESEARCH REPORT 2019/2020 could foster new ways of drug development – ProSion geführt, die innovative chemisch-biolo- from fighting viral-based infectious diseases to gische und synthetische Ansätze zur Krankheits- brain dysfunction. bekämpfung verfolgen. Beide Unternehmen sind damit ein Ausweis erfolgreicher translationaler I hope you enjoy reading it! Forschung am FMP und auf dem Campus Berlin- Volker Haucke Buch. Neben diesen Beispielen geglückter Unterneh- → Das Leibniz-Forschungsinstitut für Molekulare mensgründungen haben wir in den vergangenen Pharmakologie (FMP) hat sich in den nahezu drei beiden Jahren auch unsere Rolle als Kooperati- Jahrzehnten seit seiner Gründung als eines der onspartner der Berliner Universitäten ausgebaut. weltweit herausragenden Forschungszentren der So ist Fan Liu, Leiterin der Forschungsgruppe Molekularen Pharmakologie etabliert. Anders Strukturelle Interaktomik, seit 2020 Inhaberin einer als die meisten medizinischen Einrichtungen, die gleichnamigen Professur an der Charité-Uni- krankheits- oder indikationsbasierte pharmako- versitätsmedizin; eine gemeinsame Professur logische Forschung betreiben, verfolgt das FMP für Strukturelle Chemische Biologie mit der ein interdisziplinäres Konzept der molekularen Technischen Universität Berlin befindet sich im Pharmakologie, in welchem Forschende aus finalen Stadium der Berufung. Diese Beispiele der Strukturbiologie mit Wissenschaftler*innen illustrieren die enge Verzahnung mit den Berliner der Genetik, Physik, Chemischen Biologie oder Universitäten, aber auch mit den außeruniversi- Zellbiologie zusammenarbeiten. Das Ziel dieser tären Einrichtungen der BR50, zu denen das FMP interdisziplinären Forschung ist es, neue Ansätze gehört. der molekularen Diagnostik und Therapie zu entwickeln und so die Medizin von morgen zu Eine wichtige Entwicklung im Berichtszeitraum erschaffen. ist der weitere Ausbau von EU-OPENSCREEN, eines vom FMP initiierten europäischen Netzwerks Um am Puls der Zeit zu bleiben, ist unsere For- für Hochdurchsatz-Screening mit Sitz auf dem schung beständiger Veränderung unterworfen. Das Campus Berlin-Buch, und seiner Partnersites am betrifft sowohl die Entwicklung oder Etablierung FMP. Damit hat sich der Campus Berlin-Buch als neuer Technologien wie des CRISPR-basierten europäische Schnittstelle der screeningbasierten Genom-Engineerings oder innovativer Methoden Wirkstoffforschung etabliert. Schließlich haben der Strukturforschung als auch die biologischen FMP-Wissenschaftler*innen auch in 2019/2020 für Fragestellungen und Systeme. So haben wir im ihre erfolgreichen Arbeiten
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