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Research Area Center for Molecular Biosciences (CMBI) scientific report | 2016/2017 Scientific Coordinators Bert Hobmayer, Ronald Micura, Jörg Striessnig 2 Imprint 3 The Research Area Center for Molecular Biosciences Innsbruck (CMBI) – a life science network in western Austria In our biannual report, the Center for Molecular Biosciences of Innsbruck University (CMBI) presents its recent scientific achievements, new developments in ongoing research projects and success stories of its faculty members, especially of young researchers. Molecular biosciences represent one of the most exciting fields of modern research among the natural sciences. They bridge the gap between single molecules and the complex functions in living organisms under normal conditions and in disease. Minor changes in bioactive molecules such as DNA, RNA and proteins affect and change the properties of cells, microorganisms, animals and plants. Advances in technologies including microscopic imaging, new generation sequencing applications and techniques to analyze molecular structures result in an explosion of information and understanding of biological systems primarily oriented to improve human health. The CMBI aims at providing a platform for this extremely rapidly developing research field by taking advantage of the visibility and expertise of the CMBI’s internationally competitive groups to strengthen interdisciplinary research activities. The CMBI currently consists of 21 research teams originating from the faculties of Chemistry and Pharmacy, of Biology, and of Mathematics, Informatics and Physics, and their activities focus on research and teaching. CMBI members contribute to the FWF special research program SFB-F44 “Cell Signaling in Chronic CNS Disorders”, which is currently in its second funding period, and to several FWF-funded doctoral programs, all in collaboration with the Medical University of Innsbruck. Notably, several member labs have now initiated a first CMBI-embedded university PhD program under the topic “Ageing and Regeneration”. Furthermore, CMBI members were able to successfully compete in the recent FFG call for university infrastructure and now establish new facilities for Nuclear Magnetic Resonance (NMR) spectroscopy. These will significantly advance biomolecular structural analysis in the Western-Austrian area. In order to cross-link with the Tyrolean Life Science community and to foster career perspectives of young scientist, the CMBI is a co-organizer of the internationally visible Innsbruck Life Science meetings, and it has started to coordinate its activities as a core research unit within the newly established initiative “Tyrolean Health and Life Science Cluster”. In spite of these achievements, the CMBI faces challenges of general and also local nature. Rapid imprint | technological progress in the Life Sciences requires ongoing investments into essential state-of the art infrastructure. Ever-increasing demand for big data sets needs development of adequate computing units and bioinformatics expertise. More than half of the 21 research teams are located Content: Bert Hobmayer, Professor of Zoology Ronald Micura, Professor of Organic Chemistry together with Life Science research departments of the Innsbruck Medical University in the recently Jörg Striessnig, Professor of Pharmacology built Center for Chemistry and Biomedicine (CCB) building at the university’s central campus. Nine Layout: Stephanie Brejla, Gabi Reiter of those, however, are spatially fragmented at the Technics Campus, the Department of Botany, and the Research Department for Biomedical Aging Research. Bringing together these research Contact: Research Area Center for Molecular Biosciences (CMBI) units within a single research campus would strongly stimulate scientific interactions and facilitate the efficient use of expensive infrastructure. Long-term strategies towards this goal are needed to University of Innsbruck Innrain 80-82a enable competition with a large number of Life Science Research centers rapidly emerging across A-6020 Innsbruck Europe. All these issues require coordinated efforts at academic and political levels. Tel: +43 512 507-57501 Cover figure: Fax: +43 512 507-57599 Induced neural stem cells (iNSCs) being reprogrammed from human skin fibroblasts by the team of [email protected] CMBI group leader Frank Edenhofer. Colonies of proliferating iNSCs start to differentiate into neurons The CMBI coordinators: www.uibk.ac.at/cmbi in the periphery. Differentiating neurons exhibit characteristic outgrowth of TUJ1-positive neurites (green) that reach out to contact other neurons to build a functional network. Bert Hobmayer Jörg Striessnig Ronald Micura © 2018 by CMBI 4 Contents 5 | Overview 6 CMBI - news CMBI - specials 10 Research Summary Signal transduction in cellular growth control and 18 carcinogenesis Advanced chromatographic and spectroscopic analytical 20 tools in natural product analysis & molecular biology Characterization of RNA, proteins, and their noncovalent 22 complexes by mass spectrometry Gastropod metallothioneins in evolution: New rules for an 24 old protein family Radiation damage in biological compounds induced by low 26 energy electrons contents Regenerative potential of reprogrammed neural stem cells 28 Immuno-gerontology 30 Development of selectively acting antitumor drugs 32 Developmental biology and bioadhesion in basal animal 34 model systems Molecular and cell biology of human aging 36 Plant biochemistry and metabolism 38 Chemistry, chemical and structural biology of the pigments 40 of life Protein dynamics and biomolecular recognition 42 Developmental biology 44 Synthesis, structure, and function of non-coding RNAs 46 Cell physiology and gene regulation 48 Structure-functional activity relationship investigations on 50 ligands interacting with opioid receptors Targeted proteolysis in human diseases and its impact on 52 drug development and production Cell signaling in chronic CNS disorders 54 Pharmacognosy – combining traditional knowledge with 56 innovation Biomolecular NMR spectroscopy 58 Publications 60 CMBI - careers of young researchers 92 Awards & Honors for CMBI scientists 96 CMBI Meetings and Seminar Series 99 6 Overview Overview 7 >> CMBI facts The Research Area Center for Molecular Biosciences (CMBI) at the University of Innsbruck is an integrative and multidisciplinary research and teaching institution. The mission of the CMBI is to advance studies on the structure, function, and interaction of biological macromolecules and low molecular weight compounds relevant for cellular growth, metabolism, and development. The research activities in the CMBI take advantage of existing research strength in different fields and have strongly promoted interdisciplinary research activities in five major fields of biomolecular sciences. Basic and applied biomolecular research fields at the CMBI • Structure, dynamics and interactions of biologically important molecules • Molecular basis of physiological and pathophysiological processes • Metabolites, natural and synthetic compounds that modulate important biological processes • Cell-to-cell communication and cellular function • Development, regeneration and aging of whole organisms Twenty-one research groups from the faculty of Chemistry and Pharmacy, the faculty of Biology, and the faculty of Mathematics, Informatics & CMBI members received scientific awards and prizes over the last two Physics are members of the CMBI. years thus documenting their successful research activities also to the scientific community and general public. Among those are the Bruker research award 2017 and the Research Award of the Stiftung Südtiroler Sparkasse 2017 to Hermann Stuppner, the Edmund Optics Educational | CMBI members Areas of expertise Award Europe 2017 to Torsten Schwerte, and the Würdigungspreis des Chemistry Bundesministeriums für Wissenschaft, Wirtschaft und Forschung 2017 K. Bister, M. Hartl, E. Stefan biochemistry, molecular genetics G. Bonn, C. Huck bioanalytics to Anita Siller. Ilse Kranner was elected as President of the Austrian K. Breuker biomolecular mass spectrometry Society of Plant Biology (ATSPB). Furthermore, several CMBI members B. Kräutler, T. Müller structural biology, natural products chemistry are members of the Austrian Academy of Sciences (Kathrin Breuker, K. Liedl, D. Schuster theoretical chemistry, computer-aided molecular design Ronald Micura, Bernhard Kräutler, Jörg Striessnig) and of the German R. Micura chemical biology of nucleic acids Academy of Sciences, Leopoldina (Bernhard Kräutler, Jörg Striessnig). R. Schneider, B. Auer molecular biology, biotechnology The activities of the CMBI are currently coordinated by Bert Hobmayer M. Tollinger, C. Kreutz biomolecular NMR spectroscopy (head), Jörg Striessnig and Ronald Micura. Pharmacy R. Gust medicinal chemistry, drug design In the years 2013 - 2017 the CMBI member labs published 737 papers H. Schmidhammer, M. Spetea pharmaceutical chemistry, drug design in peer reviewed journals. This includes 28 publications in the world J. Striessnig, A. Koschak, N. Singewald cell biology, neuropharmacology leading journals Nature, Nature Structural Biology, Nature Genetics, H. Stuppner, M. Ganzera pharmaceutical biology, phytochemistry Nature Cell Biology, Nature Chemical Biology, Nature Neuroscience, members Biology Nature Communications, Nature Methods, Proceedings of the R. Dallinger cell physiology, ecotoxicology National Academy of Sciences of the United States of America, and F. Edenhofer stem cell biology
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