FOREWORD RESEARCH REPORT 2018 2019 FOREWORD THE HELMHOLTZ CENTRE FOR INFECTION RESEARCH ( HZI ) AT A GLANCE 169 Guest Researchers 58.1 802 Million € Employees Institutional Budget 1919.9 Million € Third-party Funds 66 Patent Families* (Portfolio) 505 Publications Figures for 2018 * Number of patent groups which date from one original patent application. © Jenko Sternberg Design 2 3 SITES HZI Campus Braunschweig TWINCORE, Hannover • Headquarters of HZI • Founded jointly by HZI and Hannover Medical School • Central administration (MHH) • Research infrastructure • Translational research by physicians and natural • Basic research on bacterial and viral infections, scientists immunology, anti-infective agents, epidemiology • Experimental and clinical infection research • Cooperation with the Technical University (TU) • Bridge between basic research and clinical practice Braunschweig, in particular within the Braunschweig Integrated Centre of Systems Biology (BRICS), located Helmholtz Institute for RNA-based Infection on TU main campus Research (HIRI), Würzburg • Founded jointly by HZI and Julius-Maximilian-University, Helmholtz Institute for Pharmaceutical Research Würzburg (JMU) Saarland (HIPS), Saarbrücken • Research on RNA-based mechanisms of virulence and • Founded jointly by HZI and Saarland University (UdS) host defence • Research on natural compounds, optimization for • Exploitation of RNA research for the development of pharmaceutical application new diagnostics, preventives and anti-infectives • Bridge between basic research and pharmaceutical industry Centre for Structural Systems Biology (CSSB), Hamburg Centre for Individualized Infection Medicine (CiiM), • Located on the campus of DESY (Deutsches Hannover Elektronensynchrotron) in Hamburg • Joint venture of HZI and Hannover Medical School (MHH) • Jointly operated by several north German research • Elucidation of individual characteristics relevant for institutions and universities infection susceptibility, disease progression and • Structural elucidation of molecular processes in therapeutic outcome infections using uniquely powerful photon sources • Bridging clinical practice with state-of-the-art profiling technologies and latest data science 3 Photographs of HZI’s sites: Science Campus Braunschweig-Süd: HZI | Peter Sondermann TWINCORE: TWINCORE Collection HIRI: University of Würzburg | Pressestelle HIPS: UdS | Jörg Pütz CSSB: CSSB | Tina Mavric CiiM: HDR IMAGINA Visual Collaboration 1 RESEARCH REPORT HZI 2018|2019 1 CONTENTS 5 Foreword HZI’S RESEARCH FOCI 6 About HZI 11 The Helmholtz Programme “Infection Research” 46 New Strategies against Resistant Pathogens RF AMR - Antimicrobial Resistance 53 Understanding and Influencing Bacterial IN AND AROUND HZI Interaction RF MICO – Microbial Communities 16 New Coronavirus Module in SORMAS 61 Combating Persistent Viruses 17 Meetings, Prizes, Public Outreach RF CVIR - Chronic Viral Infections Highlights of the years 2018 and 2019 67 Vaccines and Immune Therapies for High-Risk 24 “In many cases, there is no one-pill-fits-all Patients strategy” Interview with Yang Li and Marcus Cornberg, RF INDI - Individualized Immune Interventions directors of CiiM 72 Studying, Preventing and Controlling Epidemics 28 “The microbiota plays a central role in the RF EPI – Digital and Global Health onset of many diseases” Interview with microbiota researcher Till Strowig 31 “Preventive medicine is the medicine of the future” Interview with vaccine researcher Carlos Guzmán 35 “We want to understand the reasons for the different types of immune defects” Interview with Thomas Schulz, MHH, coordinator of the RESIST Cluster of Excellence 38 Joining Platforms and Forces for Novel Antibiotics HZI and Evotec establish a long-term partnership 39 From Bench to Bedside: Innovation and Translation Seed money, partnership, spinoffs: technology transfer at HZI 42 HZI’s Career Development Support for Scientists on all Levels HIGHLIGHT PUBLICATIONS PARTNERS, SITES AND NETWORKS 78 Tackling Lipid Metabolism to Control Immune 99 United in Tackling Major Challenges Reactions The German Center for Infection Research (DZIF) Luciana Berod 102 Linking Infections to Non-Communicable 80 Taking over Control: Cytomegalovirus Diseases Manoeuvres the Immune Response Research within the German National Cohort Melanie Brinkmann (NAKO) 82 Insights into the Biosynthesis of the Natural 104 In Search of Novel Anti-Infective Drugs Product Bottromycin The Helmholtz Institute for Pharmaceutical Research Jesko Köhnke Saarland (HIPS) 84 Repurposing Anti-Cancer Drugs to Combat 106 Learning the Language of RNA to Combat Antibiotic Resistance Infection Eva Medina The Helmholtz-Institute for RNA-based Infection 86 Diverse Phylogeny for Chemical Diversity: Research Würzburg (HIRI) Exploring Myxobacterial Natural Product 108 Moving into a New Era in Translational Richness Research Rolf Müller The TWINCORE Centre for Experimental and Clinical 88 From the in vivo Analysis of Infections to Infection Research a Rapid Diagnosis 110 Using Powerful Light Sources for Infection Dietmar Pieper Research 90 Challenges and Opportunities in Developing an The Centre for Structural Systems Biology (CSSB) HCV Vaccine 112 Towards Precision Medicine for Infection Thomas Pietschmann Patients 92 Dissecting the Battle between Pathogens and The Centre for Individualized Infection Medicine Host Cells at the Single Cell Level (CiiM) Antoine-Emmanuel Saliba 114 Systems Biology for Health Research and 94 Orally Bioavailable Glycomimetics Block Biotechnology Resistance-Conferring Biofilms of The Braunschweig Integrated Centre of Systems P. aeruginosa Biology (BRICS) Alexander Titz 96 Bacterial ‘Sleeper Cells‘ Evade Antibiotics and 116 Organisation Chart Weaken Defence against Infection Jörg Vogel 118 Facts and Figures 121 Publication Details FOREWARD 4 FOREWARD DEAR READERS, The new coronavirus SARS- The combination of expertise and interdisciplinary collabora- CoV-2 has shown us how fast tions at a single centre, which is unique in the field of infec- and how radically infectious tion research in Germany, positions HZI and its partners in diseases can change the world. the front line to address the global challenges arising from The COVID-19 pandemic trig- bacterial and viral pathogens. This was also recently ac- gered by this pathogen has developed an alarming global dy- knowledged during an intense and rigorous two-stage scien- namic and is going to have a massive impact on the everyday tific evaluation by international expert panels. As part of the life of people in most countries of the world. Helmholtz Association’s “Programme-oriented Funding“ pro- cess, HZI proved first its scientific excellence in March 2018 In 2018/19 – the period covered in this Research Report – and then, in November 2019, the sustainability of its central SARS-CoV-2 was barely known. It was not until the end of strategic concepts. The reviewers attested us a “world-class 2019 that a broader public became aware of the first major scientific performance” in areas such as bacterial and viral outbreak of the novel coronavirus infection in the Chinese pathogens, infection epidemiology, RNA-centered infection province of Hubei. research, as well as vaccine and anti-infective research. In particular, they highlighted the centre’s ability to bridge the The Helmholtz Centre for Infection Research (HZI) has es- gap between fundamental research and the development of tablished a translational infection research programme that potential new drugs and diagnostics, thus contributing to the enables us to rapidly respond to new challenges, such as the solution of clinical challenges such as the increasing spread emergence of novel pathogens with pandemic potential. Our of antimicrobial resistance. These results are a great encour- research strategy, which we present in this report, is based agement, putting the centre into an excellent position for its on a cross-disciplinary approach that brings together infec- future development. I would like to give my sincere thanks tious disease specialists, immunologists, epidemiologists to everybody who contributed to this tremendous success, and drug researchers to address questions of high clinical both within HZI as well as within our great network of na- need such as managing and control of the COVID-19 out- tional and international partner institutions. break. Detailed information on our cross-disciplinary priority sub- Our ability to quickly direct research efforts to tackle newly jects, the so-called Research Foci, is a central part of this arising challenges is best illustrated by the rapid adaptation report. We also provide up-to-date information about the de- of our digital infectious disease control tool SORMAS, which velopment of our sites and branch institutes, selected high- now makes it possible to provide real-time information on light publications, awards, events and partnerships. the spread of COVID-19. You will find more information on this subject and the possibilities of digital infection control I am very grateful for your interest in our research and hope in the relevant chapters of this report. Scientists at HZI will that this report will help to spread news about the huge com- continue to put enormous efforts into COVID-19 research to mitment of HZI staff and cooperation partners in their fight decipher the mechanisms of disease onset and progression against infectious disease. and to develop novel therapeutic options, also keeping in mind future epidemics. Dirk Heinz Scientific Director 4 5 ABOUT HZI