ImmunoSensation the immune sensory system Bonn cluster of excellence ANNUAL REPORT 2013 G Ap(3’-5’)G Gp(2’-5’)A A cGAMP DNA cGAS pppGp(2'-5')A GTP ATP universitätbonn ANNUAL REPORT 2013 Preface p. 8 OVERVIEW Overview: Science and Structure p. 12 Scientific Reports – Research Highlights DNA Sensing and Oxidative Damage p. 16 Local Immune Regulation in Tissues p. 24 Sterile Inflammation in the Nervous System and Metabolism p. 36 Immune Sensing and Responses in Tumor Biology p. 50 Feature Article: Immunity and Aerospace Medicine p. 56 Interviews p. 60 Dean of the Medical Faculty: Prof. Max Baur, MD p. 61 Speaker: Prof. Gunther Hartmann, MD p. 64 Vice-Speaker: Prof. Waldemar Kolanus, PhD p. 66 Postdoc: Katharina Hochheiser, PhD p. 68 PhD Student: Larisa Labzin p. 72 Head of the Flow Cytometry Core Facility: Dr. Elmar Endl p. 76 Cluster Coordination Reports p. 80 Family Support & Gender Equality p. 81 Young Investigator Support p. 86 Public Relations p. 90 Events p. 92 First Retreat of the ImmunoSensation Cluster in St. Goar p. 93 Cluster Seminars p. 95 ImmunoSensation visits ELSC/Israel p. 98 Cluster Science Day p. 102 Prizewinners of the Cluster Science Day p. 104 List of Publications p. 110 Seminars & Meetings p. 124 Prizes & Distinctions p. 128 List of Cluster Members p. 132 Biosketches p. 140 Impressions Retreat St. Goar p. 168 Organigram – Structure of the Cluster p. 170 Participating Institutions p. 172 Cluster Coordination Office (CCO) p. 174 Imprint p. 176 Preface Preface We can now look back on the first year just at the edge of a profound conceptual of funding of our Cluster of Excellence advance arising from new interactions ImmunoSensation by the German within the Cluster, such as the one Research Foundation, DFG. Within the presented in the Feature Article. One Cluster, we presented a conceptually example of the focus areas of the Cluster new view of an immune sensory system research is illustrated on the cover image. beyond the boundaries of classical immu- It is the identification of the founding nology, and it is truly exciting to see that member of a new family of metazoan our concept has found so much reso- cyclic heterodinucleotide second mes- nance within the international community. sengers, a key molecule in the DNA We also coined the term immune sensing sensing pathway. One distinguishing to draw attention to the parallels with feature of this new molecule is the 2´- other sensory systems, and what was 5´ linkage, which differs from the 3´-5´ initially deemed unconventional has now cyclic dinucleotides that are already well entered the immunological parlance. known in bacteria. This molecule is the Immune sensing is now frequently used long-sought missing piece in the puzzle worldwide and has almost eclipsed the of immune sensing of DNA (Gao et al., former term “pattern recognition”. 2013a; Ablasser et al 2013a; Civil et al., 2013; Gao et al.,2013b). In the context Within our first year, we have made of this new second messenger molecule, substantial progress in establishing a Cluster researchers also discovered a widely visible center for immunology in novel principle in innate immunity – that Bonn. Structural measures include the innate immune signals can be transferred recruitment of the first Cluster professor- via gap junctions. Gap-junction mediated ship funded by the DFG (W2 Vascular transfer of cGAMP to bystander cells Immunology, Dr. Wolfgang Kastenmüller allows a rapid transcriptional- independent from the NIH, USA), the formation of antiviral response in neighboring cells a central organizational structure, the protecting them instantly from virus in- Cluster Coordination Office, the estab- fection (Ablasser et al., 2013b). Another lishment of the International Immunology publication in this context clarified how Training Program, IITB, and the creation oxidation of self DNA can lead to autoin- of support programs such as soft skill flammatory disease (Gehrke et al., 2013). courses for students and young scientists Altogether, DNA sensing was one of the and instruments for family and gender most important topics in innate immunity support. In scientific terms, we are proud in 2013, and the contributions made by to present what has been achieved ImmunoSensation Cluster were promi- in 2013, including groundbreaking nent at an international level. discoveries as well as the development of innovative concepts and strategies which We could not have had such a success- we expect will yield novel insights in the ful year without the collaborative effort of coming years. all our members. We would like to thank our scientists, young and “old”, for their Exciting work has been done in the enthusiasm and hard work in 2013. We Cluster, some of which is published in thank the managerial team behind the 2013 and reported in the following chap- Cluster for its great track record after only ters. Other innovative project areas are one year. We are grateful for the support 9 that we have received from the DFG and This is comparable to other classical from the University of Bonn, specifically sensory systems that operate constantly Picture the Faculty of Medicine and the Faculty of without us taking notice of them. Intact Prof. Dr. Gunther Hartmann Mathematics and Natural Sciences. The and synchronized communications and cooperation within the Cluster between connections of the immune system to the University and our two extramural other processes and structures of our institutions, the Max Planck Society- body, like metabolism or the nervous associated center of advanced european system, are crucial to balance immune studies and research (caesar) and the activity and to maintain health. German Center for Neurodegenerative Diseases (DZNE) has been central to To efficiently investigate the complex breaking new ground in research on the network of the immune sensory immune sensory system. Finally, there system, research groups from different is a great sense of scientific community disciplines are working together with- in Bonn that extends beyond group, in the ImmunoSensation Cluster. The institutional and national borders. It is Medical Faculty is leading this initiative this atmosphere that makes science at jointly together with LIMES (Life and ImmunoSensation so vibrant, dynamic Medical Sciences Institute) of the Faculty and enjoyable. of Mathematics and Natural Sciences. (For references see Cluster publication list 2013.) Immunologists closely work together with groups of genetics, biochemistry, biophysics, cell biology, neuroscience, Overview Science and Structure and mathematics. The participation of research groups from the clinical de- The concept of the ImmunoSensation partments foster translational research. Cluster is to address the immune system Besides the University of Bonn, the Max as a complex, yet incredibly efficient Planck Society-associated center of sensing device, which displays multiple advanced european studies and research characteristics of a sensory organ. (caesar) and the German Center for Specialized receptors are in charge of Neurodegenerative Diseases (DZNE) are sensing damage or danger, such as the equal partners of the Cluster. The German receptors of the innate immune sys- Aerospace Center (DLR) and the Hebrew tem, which are inherited and present University in Israel are Cluster- associated from birth on. In addition, there are the institutions. The Cluster closely cooper- highly variable receptors of B- and T ates with international research partners cells that are acquired later in life, and and institutions from the USA, UK, which are characterized by constant Ireland, Israel, and Japan. renewal. Immune sensing receptors are not restricted to immune cells. Some Prof. Dr. med. Gunther Hartmann of them are expressed in a wide range Speaker of human somatic cell types. They rep- resent the center core of a multimodal sensory system that is well-equipped to distinguish self from non-self as well as harmless from harmful. An exact analysis and signal integration of the sensed information is essential in order to coordi- nate and execute an appropriate immune reaction and to protect the organism from damage. In healthy organisms, these sensing mechanisms are continuously active beyond the level of our awareness. 10 11 Overview: ImmunoSensation Cluster of Excellence Science and Structure an Introduction: Interview with Prof. Gunther Hartmann Speaker of the ImmunoSensation Cluster ImmunoSensation: and mathematics at the University of Interview with Prof. Hartmann, what is the research Bonn collaborate closely with research focus of the ImmunoSensation Cluster of on neurodegeneration at the DZNE and Prof. Dr. med. Excellence? the research on biophysics and molecular Gunther sensory systems at caesar. We also work Hartmann Gunther Hartmann: together with international collaboration Our approach is to view the immune partners in the USA, UK, Ireland, Israel system as an immune sensory system, and Japan. in other words as an organ of perception that uses receptors to sense pathogens and cellular damage. This system should ImmunoSensation: be seen in a broader context than just im- What exactly is meant by “the immune mune cells, since these immune sensing system as a sensory organ”? What is the receptors are not restricted to immune connection to the other systems in the cells and therefore this concept reaches body? beyond the classical immune system. We are also beginning to understand the Gunther Hartmann: extent to which the immune system is For most sensory organs, the signal