RESEARCH REPORT 2015 / 2016 SCIENTIFIC ADVISORY BOARD Prof. Dr. Karl-Heinz Altmann Prof. Dr. Stefan Offermanns Institut für Pharmazeutische Max-Planck-Institut für Herz- und Wissenschaften, ETH Zürich Lungenforschung, Bad Nauheim (seit 01 / 2012) (seit 01 / 2016) Prof. Dr. Nils Brose Prof. Dr. Petra Schwille (Vorsitzender) Max-Planck-Institut für Biochemie, Max-Planck-Institut für Experimentelle Martinsried Medizin, Göttingen (seit 01 / 2012) (seit 01 / 2012) Prof. Dr. Rebecca Wade Prof. Dr. Ulrike Eggert (Stellvertretende Vorsitzende) Randall Division of Cell and Molecular Heidelberg Institute for Theoretical Biophysics, King´s College London Studies, HITS gGmbH (seit 01 / 2013) (seit 01 / 2013) Dr. Matthias Gottwald Bayer Pharma AG, Berlin (seit 01 / 2016) Prof. Dr. Thomas Gudermann Walter-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München (seit 01 / 2013) Prof. Dr. Eckart Gundelfinger Leibniz-Institut für Neurobiologie, Magdeburg (seit 01 / 2013) Prof. Dr. Gerhard Klebe Institut für Pharmazeutische Chemie, Universität Marburg (seit 01 / 2009) Prof. Dr. Beat Meier Laboratorium für Physikalische Chemie, ETH Zürich (seit 01 / 2013) Stichtag 31.12.2016 RESEARCH REPORT 2015 / 2016 2 RESEARCH REPORT FORSCHUNGSBERICHT 2015 / 2016 CONTENTS INHALT PREFACE Interview with Director Dorothea Fiedler VORWORT What's new at the FMP? Was ist neu am FMP? 4 RESEARCH HIGHLIGHTS The cause of muscle weakness reveals the organisational principle in cells AKTUELLES AUS Ursache von vererbter Muskelschwäche aufgeklärt 8 DER FORSCHUNG Milestone for Parkinson's research: The amyloid protein α-synuclein is visualised in the cell for the first time Meilenstein für die Parkinson-Forschung: Amyloid-Protein α-synuclein erstmals in Zelle sichtbar gemacht 9 Double mechanism confirmed: How inositol pyrophosphates alter proteins Doppelter Mechanismus bestätigt: Wie Inositol-Pyrophosphate Proteine verändern 10 Interview with Thomas J. Jentsch "We've pushed the door wide open to novel biomedical insights" „Wir haben die Tür für neue biomedizinische Erkenntnisse aufgestoßen“ 11 CONTENTS INHALT 3 RESEARCH GROUPS Section Molecular Physiology and Cell Biology FORSCHUNGSGRUPPEN Bereich Molekulare Physiologie und Zellbiologie 14 Physiology and Pathology of Ion Transport Thomas J. Jentsch 20 Molecular Pharmacology and Cell Biology Volker Haucke 24 Protein Trafficking Ralf Schülein 28 Molecular Cell Physiology Ingolf E. Blasig 31 Molecular Neuroscience and Biophysics Andrew J.R. Plested 34 Membrane Traffic and Cell Motility Tanja Maritzen 37 Proteostasis in Aging and Disease Janine Kirstein 40 Behavioural Neurodynamics Tatiana Korotkova / Alexey Ponomarenko 43 Molecular and Theoretical Neuroscience Alexander Matthias Walter 46 Cellular Imaging Burkhard Wiesner / Dmytro Puchkov 49 Animal Facility Natali Wisbrun 52 Section Structural Biology Bereich Strukturbiologie 54 Molecular Biophysics Adam Lange 60 NMR-Supported Structural Biology Hartmut Oschkinat 64 Solution NMR Peter Schmieder 68 Computational Chemistry / Drug Design Ronald Kühne 71 Structural Bioinformatics and Protein Design Gerd Krause 74 In-Cell NMR Philipp Selenko 77 Molecular Imaging Leif Schröder 79 NMR Hartmut Oschkinat / Peter Schmieder 82 Section Chemical Biology Bereich Chemische Biologie 86 Chemical Biology II Christian P. R. Hackenberger 92 Chemical Biology I Dorothea Fiedler 96 Peptide-Lipid Interaction / Peptide Transport Margitta Dathe 100 Mass Spectrometry Eberhard Krause 103 Medicinal Chemistry Marc Nazaré 106 Screening Unit Jens Peter von Kries 109 Peptide Synthesis Rudolf Volkmer 112 APPENDIX All Research Groups 116 ANHANG Map Campus Berlin Buch 118 Administrative and Technical Services 120 Imprint 4 RESEARCH REPORT FORSCHUNGSBERICHT 2015 / 2016 WAS IST NEU AM FMP? WHAT´S NEW AT THE FMP? Prof. Dr. Dorothea Fiedler Director at Leibniz-Forschungsinstitut für Molekulare Pharmakologie Dorothea Fiedler has been director at the FMP since July are trying to decode cellular processes at the molecular level. For me as 2015. In an interview, she speaks about her move from the a chemist that's really exciting. One focus of our work are the so-called USA to Germany, the focus of her research and about current inositol pyrophosphates. These molecules are messenger substances in developments at the FMP. the cell that, for example, play an important role in disorders of fat meta- bolism and insulin secretion, but also have an influence on cell migration, Professor Fiedler, you were a distinguished scientist in the specifically metastasis. In effect we are trying to understand the language USA, latterly at Princeton University, and have received of chemistry and thus hope to lay the foundations for new therapies. numerous awards. What motivated your move to Berlin-Buch? There were several reasons. The most important one was undoubtedly Is it the promise of new therapies that motivates you to conduct that the FMP is an excellent institute, where interdisciplinary research basic research? is conducted at the interface of biology and chemistry. To this extent, The desire to improve the health of humankind is fundamental to all of us. the science at the institute was a perfect match. In addition, I can Admittedly, most of the groups at the FMP are not developing therapies collaborate with outstanding people here, both internally and exter- in an actual sense, but it is the basic research conducted at the Institute nally. And then the FMP offers exceptional research conditions. All of that paves the way. This can be seen, for example, in the fact that two this was simply too tempting for me to turn down the offer of a W3S spin-offs from the Hackenberger and Kühne groups are in preparation. professorship linked to the post of director, although I was very happy in the USA. One-third of the research groups at the FMP are junior groups. What's new here? Together with Professor Volker Haucke you form a dual lead- A great deal. In the field of molecular physiology and cell biology, ership at the FMP. How do you divide up this important task? there is a new liaison group, “Neurosciences”, the Emmy Noether There was a clear agreement that I would officially take over the Junior Group led by Alexander Walter. In addition, our junior group management after 18 months. That is now the case as of 1 January, leader Andrew Plested has been offered a Heisenberg professorship but we continue to complete many tasks together and always consult at the Humboldt University. His group will remain at the FMP as each other on important decisions. a guest group for an additional five years. In contrast, we will have to say farewell to Philipp Selenko this year. He has successfully led You are responsible for 300 employees. Is there any time left a junior group in structural biology for several years and has now to do your own research in the laboratory? accepted an attractive offer from the Weizmann Institute of Science Unfortunately, it has been a while since I ran experiments in the in Israel. It is all the more pleasing that a new junior group at the laboratory. But at this point, my co-workers can carry out the work interface of NMR and Cryo-EM is to be established in this better than me. But naturally I still work closely with my PhD important field of research, this being within the context of the students and postdocs. Research is and will certainly remain the planned “Cryo-EM infrastructure”, in which the Berlin Universities part of my work that I enjoy the most. and the MDC will also be involved. Our doctoral students are very successful as well, for instance Jean-Philippe Demers from the What does a professor of chemical biology conduct research on? department of Adam Lange received the Raymond Andrew Prize and In many areas of cell biology we have now arrived at a point where we the Otto Hahn Medal in 2015, a really remarkable accomplishment. WHAT'S NEW AT THE FMP? WAS IST NEU AM FMP? 5 Matthias Schnurr, Honor Rose, Jabadurai Jayapaul Our junior group leader Leif Schröder established a co- I think, and I can speak for the past and for the future, that the operation with the California Institute of Technology in Pasadena FMP is an institute that places special value on modern methods to develop ultra-sensitive magnetic resonance imaging, which and technology. With this strategy, and of course driven by our allows to detect tumours, for example. At the same time, last excellent scientists, we will in the long run secure pioneering results year, he secured a Reinhart Koselleck-Project of the Deutsche that will be of benefit to the scientific community and ultimately Forschungsgemeinschaft (DFG) for a similar undertaking. The to society. What I would like to see is more international visibility. funding amounts to 1.525 million euros and was the first ever The FMP is very well connected throughout Germany and also Koselleck Project for the Leibniz Association. I find all of this quite internationally. Nevertheless, the Institute, like the Leibniz Association, outstanding. is not yet as well known internationally as other German research organisations. We're working on that. At the beginning of this year, there was then a second Reinhart Koselleck-Project for the FMP and a small sensation for the Dorothea Fiedler ist seit Juli 2015 Direktorin am FMP. Im Institute? Interview spricht sie über ihren Wechsel von den USA nach That's right, just a few months later, Volker Haucke impressed the Deutschland, ihre Forschungsschwerpunkte und über aktuelle DFG with his application for research into neuronal communication. Entwicklungen am FMP. We are very proud of that. Both awards show the high level of research at the FMP. As early as 2015, Philipp Selenko and Andrew Plested Frau Professor Fiedler, Sie waren in den USA, zuletzt an der were awarded the prestigious “Consolidator Grant” of the European Universität Princeton, eine angesehene Wissenschaftlerin Research Council (ERC) for their research work. Over the past five und haben etliche Auszeichnungen erhalten. Was hat Sie years, Thomas J. Jentsch successfully applied for these most prominent nach Berlin-Buch verschlagen? and coveted programmes offered by the European Commission, for his Es waren mehrere Gründe.