2012 – 13 BIENNIAL REPORT
YOUNG TALENT 3 YEARS OF RESEARCH SCIENTISTS MANAGEMENT HELENA HIGHLIGHTS Junior research groups Specific training International success Selected publications as opportunity for for science and model Helmholtz Grad- from the research young researchers administration uate School Environ- programs mental Health At a glance. Helmholtz Zentrum München is currently organized in 39 research institutes trans- and independent units, which are linked via programs and topics. The Center has various technology platforms and central service units. In order to information lational facilitate the transfer of results from basic research into medical applications, services scientists of Helmholtz Zentrum München collaborate closely in translational 2 i centers centers and clinical cooperation groups with medical partners at Munich’s 3 universities and hospitals. 328 doctoral students 22
joint appoint- 39 11 institutes and clinical ments with the employees cooperation groups Munich elite independent 2234 universities research units 19 150 junior research 18 spin-offs since 1997 patent families groups 1062 1178 224 publications in publications in million 63 international international euros trainee places journals 2012 journals 2013 finance volume 2013 in 8 professions 3
Biennial Report 2012-2013 CONTENTS CONTENTS 4 5 Table of Contents
6 EDITORIAL 50 RESEARCH IN SCIENTIFIC PROGRAMS 77 Faster Production of Disease Models 100 INNOVATION AND TRANSLATION
Promotion of Young Scientists at Helmholtz Zentrum Major Common Diseases and the Role of Genes and 78 Human Glial Cells Can Be Reprogrammed From Basic Research to Applications München – a Success Model the Environment Examples of promising approaches for therapy Programs at the Center and their integration into the 79 Trnp1 Regulates Expansion of Mammalian and prevention research areas of the Helmholtz Association Cerebral Cortex 8-15 TIMELINE 2012–2013 104-105 Antipsychotic Drugs Tested Against Malignant 80-81 How Roquin Family Proteins Control T Cells Lymphomas Overview of events at the Center 52 RESEARCH HIGHLIGHTS Daniel Krappmann 82-83 Personalized Leukemia Therapy Appears within Reach IMPORTANT RESULTS 2012/2013 106-107 Spearhead of Diabetes Prevention 16-27 INTERVIEWS WITH THE MANAGING DIRECTORS We present selected examples from the 84-85 Further Decryption of the Epigenetic Code Florian Haupt, Ruth Chmiel 2240 publications of the last two years Challenges and Perspectives 86 Intellectual Disability Is Caused by Günther Wess, CEO, Nikolaus Blum, CFO, and 54-55 Brain Signal Regulates Body Weight Spontaneous Mutation 108 TALENT MANAGEMENT Alfons Enhsen, CTO, comment on the future development of Helmholtz Zentrum München 56 Hormones against Metabolic Syndrome 87 New Insights into the Genetic Mechanisms Qualification Training at the Center of Red Blood Cell Formation Strategic personnel management develops target 57 Hormone Duo Promotes Loss of Fat Reserves group-oriented employee competence 28 MAIN THEME: 88-89 DNA Methylation Plays Important Role PROMOTION OF YOUNG SCIENTISTS 58 Predictive Biomarker for Gastric Bypass in Human Metabolism 112-113 Recruiting and Promoting Talent in Science Administration 30-31 Countries of Origin of HELENA Doctoral Students 59 Evolution of Energy Metabolism 90 Detecting the Identities of “Unknown Metabolites” Barbara Ferwagner, Theresia Schmitt, Uwe Bott
32-35 Three Years of HELENA 60-61 Biomarkers of Pre-diabetes 91 Two Imaging Modalities Better Than One Doctoral training plus leadership skills 114 FACTS & FIGURES 62 Role of Genetics in Type 2 Diabetes Pathogenesis 92-93 Lifestyle Factors affect Metabolite Profile 36-37 Portraits of Junior Research Groups Administrative Statistics for 2012 and 2013 We present six of the 19 junior research groups 63 Relationship between PTSD and Type 2 Diabetes 94-95 Bioinformatics for Stem Cell Research Increase in number of staff and successful at Helmholtz Zentrum München grant acquisition 64-65 Breastfeeding Reduces Risk of Type 2 Diabetes 96 Mapping of the Barley and Bread Wheat Genomes 38-39 Insights into the World of Mitochondria 116-117 Staff Fabiana Perocchi 66 Air Pollution Promotes Insulin Resistance 97 Casting Light on the Evolution of Nightshades 118-119 Finances 2012 40-41 Peacekeeping Troops of the Immune System 67 Type 1 Diabetes Is Predicted by Autoantibodies 98-99 How Roots Branch Out against Type 1 Diabetes 120-121 Finances 2013 Carolin Daniel 68 Progression of Type 1 Diabetes 122-125 Project Funding and Research Cooperations 42-43 Communication Factors under Surveillance 69 Infections Increase Type 1 Diabetes Risk Stefanie Eyerich 70 Interplay of Cytokines in Asthma 126 ORGANIZATION 44-45 Searching for the Origin Micha Drukker 71 More Risk Genes for Allergies Research Units, Management and Advisory Bodies Research structure and overview of contact 46-47 Proteins under the Hammer 72-73 Cost of Medical Care in Early Stages of COPD persons and addresses Tobias Madl 74-75 Key to Neurogenesis 128-131 Institutes, Departments, Research Units 48-49 Signals for the Protection of Plants and Translational Units Corina Vlot-Schuster 76 Oligodendrocytes and Multiple Sclerosis 132-133 Organization EDITORIAL EDITORIAL 6 7 Promotion of Young Scientists at Helmholtz Zentrum München – a Success Model
An important component of talent management at Helmholtz Zentrum München is the promotion of well-trained science administrators, who serve as bridge between the needs of the research and the requirements of the administration. Oriented on the Helmholtz Zentrum München has consolidated its position as one of the world’s leading strategic objectives of its research, the Center offers its young professionals in science, institutions in the field of health and the environment. In summer 2013 this was the administration and infrastructure a wide range of qualification opportunities. On page assessment of the expert review for the third period of program-oriented funding, 112 you can read how Helmholtz Zentrum München promotes talented young people which provides the framework for our scientific work. In its review report, the panel of in science administration. international experts commended the Center for its outstanding research achievements and strategic positioning. In addition, the reviewers specially commended the Center’s Of course, the focus of our work is on successful research and the publication of research efforts to promote young scientists. In particular, they pointed to the Helmholtz Graduate results in international journals. Both the number of publications and their impact School Environmental Health (HELENA), established only three years ago together with ranking have risen steadily in recent years. In 2012, 1062 publications with 6298 impact Technische Universität München and Ludwig-Maximilians-Universität, as an international points resulted from research at the Center. In 2013 the publication output increased success model. Currently, approximately 330 young people are working under the to 1178 publications and 7568 impact points. Since 2005 the Center has nearly doubled umbrella of HELENA in interdisciplinary teams toward their PhD degrees and are the number of its publications and has tripled its impact factors. As highlights of the acquiring additional skills for future leadership positions in science and industry. Center’s scientific work, we present 34 selected publications starting on page 54.
As a major theme in this biennial report, we present examples of our successful Research at Helmholtz Zentrum München has successfully met the criteria of scientific training program for young scientists. Read on page 32 how doctoral students use evaluation. In doing so, the Center has never lost sight of its overarching objective: the opportunities of the Helmholtz Graduate School Environmental Health to begin to contribute to a better understanding of gene-environment associated diseases and their academic or professional careers. to the development of new therapies – especially for widespread common diseases such as diabetes, lung diseases and allergies. To ensure that progress in knowledge Another focus of the promotion of young scientists at Helmholtz Zentrum München is on rapidly benefits society, translational research and innovation are key elements of our the appointment of talented young researchers to head their own junior research groups. strategy. Two examples of particularly promising approaches in cancer treatment and Equipped with their own budgets and with responsibility for their own staff, the for the prevention of type 1 diabetes can be found on page 104. researchers can establish themselves internationally in their subject area within a period of five years. In 2012 and 2013, 13 junior research groups were launched. In 2013 Helmholtz Zentrum München achieved outstanding results in the review of its Altogether, there are 19 junior research groups at the Center, 13 of which are headed content and strategic development as well as its repositioning within the framework of by women. Seven of these are funded by Starting Grants of the European Research program-oriented funding. Our task in the coming years will be to retain this position Council. Starting on page 38 we present six junior research groups. At the same time, and to expand it further. Managing Directors Prof. Dr. Günther Wess, Dr. Nikolaus Blum each portrait stands for a topic of the research programs of the Center. and Dr. Alfons Enhsen explain in interviews starting on page 16 how we shall approach and master this task and describe the challenges that may lie ahead. At the end of 2013, the Center closed a gap in its strategic concept to promote young scientists with the first call for applications for an international postdoctoral program. The Board of Directors would like to take the opportunity here to express its thanks Up to 16 excellent young scientists will develop and implement their personal career to all employees of the Center and to the members of the Supervisory Board and the plan over the course of three years, within the framework of this program and with the Scientific Advisory Board. All have contributed to the successful positioning of the support of scientific mentors and personal coaches. Center internationally and to strengthening the Center for the future. The Editors TIMELINE 2012 TIMELINE 2012 8 9
JANUARY 26th MARCH 27th APRIL 26th MAY 19th JULY 1st Timeline 2012 Good Clinical Practice: The Center Exploring the workplace: On nation- Three prizes for diabetes research at establishes an internal policy for the wide “Girls' Day”, 50 school students the Center: At the annual meeting of production of clinical trial samples gain insight into scientific work at the German Diabetes Society Prof. Dr. and for studies that are carried out Helmholtz Zentrum München. Matthias Tschöp receives the Werner JANUARY 1st together with clinical partners. Creutzfeldt Prize, which is endowed MAY 2nd with 10 000 euros. Dr. Christiane FEBRUARY 1st Winkler receives the Ernst Friedrich Pfeiffer Prize, likewise endowed with Personalized therapies for diabetes: 10 000 euros, and Dr. Maren Pflüger Successful completion of apprentice- Helmholtz Zentrum München partici- Presentation in Berlin of collabo- receives the Silvia King Award for ship: The biology laboratory assistants pates in the DIRECT project, which is rative lung research success: The achievements in clinical diabetology. Bianca Vogel, Sandra Lubos and funded by the Innovative Medicines Parliamentary State Secretary in the Kristina Steigerwald have successfully Initiative (IMI) with 45 million euros. Federal Ministry of Education and JUNE 15th completed their three-year vocational Research Dr. Helge Braun and the training. The office administrators The Center expands allergy research: FEBRUARY 4th spokesperson of the German Center Outstanding ranking: The epidemiol- Franziska Kölbl and Evelyn Thiel as Under the direction of Prof. Dr. for Lung Research, Prof. Dr. Werner Experts answer questions: The ogist Dr. Joachim Heinrich is ranked well as warehouse logistics special- Carsten Schmidt-Weber – who at the More intensive collaboration with Seeger, present novel approaches second patient forum of the Lung 12th in the world among most cited ist, Michaela Laumeyer have also same time holds the Chair of Molec- INSERM: Researchers from Helmholtz to treat lung diseases. Photo: Ingo Information Service informs about authors of asthma publications in the completed their apprenticeships with ular Allergology and Environmental Zentrum München and the French Kniest childhood bronchial asthma at the field of lung and respiratory research top grades. Research at Technische Universität Institut National de la Santé et de Comprehensive Pneumology Center. and 2nd among the German-language München – the newly founded Insti- la Recherche Médicale (INSERM) APRIL 12th authors after the former director of JULY 10th tute of Allergy Research is launched. coordinate projects within the graduate MAY 3rd the Institute of Epidemiology, Prof. program “Lung Biology and Disease”. Dr. Dr. H.-Erich Wichmann. Setting the course for the future: The JANUARY 3rd The Helmholtz Research School of Scientific Advisory Board endorses FEBRUARY 13th Radiation Sciences is established: The JUNE 25th the Center’s strategies and concepts Focus on aerosols and health: To new graduate school in a joint endeavor of its environmental health portfolio, investigate the effects of anthropo- with the two Munich universities offers public health and personalized med- genic particulate matter, Helmholtz places for 25 PhD students and is part icine as well as their inclusion into Zentrum München, the University of of the Helmholtz Graduate School the program-oriented funding of the Rostock and six other international Environmental Health (HELENA). Helmholtz Association (POF III). partners join together to form the The Central Energy Facility celebrates Helmholtz Virtual Institute of Com- its topping out ceremony: With the MAY 15th JULY 13th plex Molecular Systems in Environ- expansion of its utility infrastruc- mental Health (HICE). tures, the Center creates important Intensified cooperation: Under the Green light for the specimen bank: McCulloch and Till Award for Dr. conditions for the development of its leadership of its president Prof. The Supervisory Board approves the JANUARY 21st Timm Schroeder: The head of the Neuherberg research campus. Chunli Bai, a delegation of the Chinese establishment and operation of the independent Department of Stem Academy of Sciences informs itself biorepository for the National Cohort Outstanding achievement for epi- Cell Dynamics at Helmholtz Zentrum APRIL 19th about possibilities for expanding on the Neuherberg research campus. demiologist at the Center: Dr. Jakob München is awarded the prize of the partnerships with Helmholtz Zentrum Linseisen places second in Labor- International Society for Hematology München. JULY 15th journal’s publication ranking of most and Stem Cells for Young Scientists. cited German scientists in the field of Alexander von Humboldt Professor- JUNE 29th nutrition research. FEBRUARY 17th ship awarded to Matthias Tschöp: Federal Research Minister Dr. Annette JANUARY 25th Value creation strengthened: In addi- Schavan presents the most highly tion to early-stage projects with value endowed international award for re- creation potential, the Department of search in Germany to the director of Innovation Management, headed by the Institute for Diabetes and Obesity Dr. Annette Janz, is now also respon- and chair of Metabolic Diseases at sible for the patenting and commer- Technische Universität München. Investigation of the mechanisms of cialization of innovative know-how. T cell tolerance: The Research Unit Diabetes institutes in Garching opened: Molecular Immune Regulation, First official visit to the Zugspitze: The Until the completion of the diabetes headed by Dr. Vigo Heissmeyer, Bavarian State Minister for Health and building in Neuherberg, the Institute begins operations. the Environment Dr. Marcel Huber for Diabetes and Obesity and the Lung Information Service at the informs himself in the environmental Institute of Diabetes and Regeneration Center receives ARTs and AIR research station Schneefernerhaus Research are located on the Garching AWARD: The award, conferred by the about the contributions of Helmholtz Business Campus. AtemWeg Foundation and Münchner Zentrum München to the European Bank for special projects in lung Virtual Alpine Observatory. research, commemorates the artist Christoph Schlingensief, who died of lung cancer. TIMELINE 2012 TIMELINE 2012 10 11
AUGUST 1st OCTOBER 4th NOVEMBER 14th Timeline 2012 New trends in pulmonary medicine: Launch of international competition The second Munich Lung Conference for Health and Environment Funding: begins under the auspices of the Com- The Center funds internal projects on prehensive Pneumology Center (CPC). environmental health problems in the JULY 18th fields of allergies, the microbiome OCTOBER 22nd and health as well as nanoparticles with up to 180 000 euros per year. The challenge of obesity: Within Start of research campus: 50 children the framework of the World Health NOVEMBER 23rd of staff take part in two-week holiday Summit in Berlin, CEO and Scientific research program for kids on campus. Director Prof. Dr. Günther Wess mod- Strategic alliance against obesity and erates the discussion of renowned diabetes: Helmholtz Zentrum München AUGUST 14th scientists. and Sanofi Aventis arrange a research The Department of Environmental alliance for new targets and screening Sciences begins work: The merger of Now a total of eight ERC Starting NOVEMBER 5th methods to develop innovative therapy seven research units contributes to the Grants at the Center: The European approaches. synergistic effects of environmental Research Council (ERC) awards a 1.5 Epigenetic research receives VdFF and health research at the Center. million euro grant to Prof. Dr. Gil Gregor Research Award: The Association of NOVEMBER 26th Westmeyer of the Institute of Bio- Friends and Sponsors (VdFF) awards JULY 19th logical and Medical Imaging and the a prize for interdisciplinary cooper- Institute of Developmental Genetics ation to a paper which appeared in to develop new methods of imaging Science in 2012 on the function of molecular processes in the brain. cell memory.
AUGUST 28th NOVEMBER 6th
Beyond Big Data: With Clueda AG, a Graduate Students' Day: Prof. Dr. new spin-off company from Helmholtz Erwin Neher, Nobel Laureate in 1991, B2RUN corporate running competition Zentrum München is launched. It holds a Career Lecture. in Munich: 168 runners from Helm- develops software tools to strongly holtz Zentrum München take part in increase applicable knowledge and to NOVEMBER 12th HICE Biomobile starts on first meas- the sports event in the Olympia Park. read complex situations quickly. uring campaign: At four European Balancing career and family: The first stations, scientists of Helmholtz JULY 23rd SEPTEMBER 14th parent-child room for short-term care Zentrum München, the University of needs is opened on campus. Rostock and their partner institu- Diabetes Information Service online: tions study the effects of particulate Under www.diabetesinformations NOVEMBER 13th matter on lung cells. dienst-muenchen.de the Center makes information about diabetes available Campus Park takes form: With DECEMBER 10th to the general public. terrain modeling, work begins on the two-hectare meeting and recreation Rapid publication of research results: JULY 24th space. Helmholtz Zentrum München and the German Center for Diabetes Research Top marks for the administration: MELODI Award for Dr. Kristian Unger: at Campus Neuherberg are partners in A nine-member panel of external The scientist of the Research Unit of the publication of the newly estab- experts presents its results of the Radiation Cytogenetics receives in lished open access journal Molecular review of planning, managing and Helsinki the Multidisciplinary European Metabolism. support processes to the staff of the Low Dose Initiative Prize, which is Center. endowed with 4000 euros.
SEPTEMBER 20th
Development of young scientists is strengthened: The Helmholtz Associ- ation announces funding of two new junior research groups led by Dr. Stefanie Eyerich and Dr. Claudia Plant. TIMELINE 2013 TIMELINE 2013 12 13
JANUARY 15th MARCH 1st MARCH 21st MAY 1st MAY 30th Timeline 2013 The Center expands its diabetes Gain for lung research: Prof. Dr. Jürgen Review successfully completed: Leading virologists in Munich: Upon research capacity: The official opening Behr assumes the Chair of Pneumology Reviewers commend international invitation of the Institute of Virology of the Institute of Diabetes and Regen- at Ludwig-Maximilians-Universität visibility and high strategic value of of Helmholtz Zentrum München and eration Research, directed by Prof. Dr. München and becomes Director of "Sustainable Plant Production" and Technische Universität München, the JANUARY 1st Heiko Lickert, takes place in Garching. Clinical Pneumology at the Comprehen- "Sustainable Water Management", Global Virus Network discusses new Lickert also holds the Chair of Diabetes sive Pneumology Center of Helmholtz two topics coordinated by the Center insights concerning the fight against Coordinating role for the research Research/ Beta Cell Biology of Technis- Zentrum München, the LMU University in the POF program "Terrestrial virus-associated infectious diseases. field of Health: the CEO and scien- che Universität München. Hospital and Asklepios Specialist Environment". tific director of the Center, Prof. Dr. Clinics in Munich-Gauting. Institute of Computational Biology is JUNE 1st Günther Wess, takes office as scien- JANUARY 23rd MARCH 25th established: Prof. Dr. Dr. Fabian Theis tific vice president of the Helmholtz MARCH 16th becomes director of the new institute Two new junior research groups at Association and coordinator for the Funding notifications received: Development of the microscope of at Helmholtz Zentrum München and the Center: Dr. Jantje Mareike Gerdes research field of Health. Helmholtz Zentrum München, Leibniz the future: The Federal Ministry of also assumes the Chair of Mathemat- heads the newly founded junior Institute of Plant Genetics and Crop Education and Research promotes the ical Models of Biological Systems at research group “Primary Cilia and JANUARY 3rd Plant Research (IPK) Gatersleben and research cooperation ‘Tech2See’ of the Technische Universität München. Energy Metabolism” at the Institute of Forschungszentrum Jülich participate Institute of Biological and Medical Diabetes and Regeneration Research. Helmholtz researchers appointed to in the German Plant Phenotyping Imaging of Helmholtz Zentrum MAY 1st At the same time, the research group Radiation Protection Commission: Network (DPPN) of the Federal Minis- München together with ZEISS and “Mechanisms of Gene Regulation in Prof. Dr. Werner Rühm, head of the try of Education and Research. iThera Medical GmbH. Management expanded: Dr. Alfons T cells" led by Dr. Elke Glasmacher research group Personal Dosimetry of Enhsen takes up his duties as man- begins work at the Institute for the Institute of Radiation Protection, JANUARY 30th Event to inform patients: 250 partici- APRIL 4th aging director for the scientific-tech- Diabetes and Obesity. belongs to the committee Radiation pants attend the first Patients‘ Day of nical infrastructure at Helmholtz Risk and Dr. Werner Kirchinger, com- Vocational training completed: Michael the Diabetes Information Service con- One hundred mark passed: The Zentrum München. JUNE 4th pany and fire department physician Opitz, Willi Grätz, Markus Fischer and cerning the disease diabetes mellitus. Center participates in more than 100 and head of the Regional Radiation Alexander Felber successfully complete projects within the Seventh Research MAY 5th Research supports environmental Protection Center, belongs to the their final examination to become MARCH 19th Framework Programme of the Euro- policy: Prof. Dr. Annette Peters, direc- committee Emergency Response. biology laboratory technicians. pean Union, acquiring more than 50 Environmental biologist in the Top tor of the Institute of Epidemiology II, million euros in third-party funding 50: Prof. Dr. Michael Schloter, head of presents the current status of knowl- for this purpose. edge on the impact of air pollution on JANUARY 8th FEBRUARY 14th the Research Unit of Environmental health at the Green Week Conference Genomics, is 22nd in the Laborjournal Joining forces for personalized 2013 in Brussels. APRIL 6th ranking of the most cited researchers medicine: As first German research in the field of microbiology. institution, Helmholtz Zentrum JUNE 21st München joins the Personalized Med- MAY 9th icine Coalition (PMC), an international TransAqua is launched: Four insti- consortium of research, industry and tutes of Helmholtz Zentrum München patient organizations. Federal Minister Prof. Dr. Johanna participate in the joint project for the Wanka confers Leibniz Prizes: Prof. Dr. transfer of radionuclides in aquatic Cooperation partners of the Center FEBRUARY 20th Vasilis Ntziachristos, director of the ecosystems, which is funded by the honored with Helmholtz Interna- Institute of Biological and Medical Im- Federal Ministry of Education and tional Fellow Awards: The Helmholtz With top marks to POF III: International aging at Helmholtz Zentrum München Research with four million euros. Association conferred the awards, reviewers convince themselves of the and professor of Biological Imaging China Scholarship Award for biologist which are endowed with 20 000 quality and strategic relevance of the at Technische Universität München is of the Center: Dr. Jin Zhao of the Insti- JULY 1st euros each, to Prof. Dr. Harald von new research program Genes and En- recipient of one of the prizes endowed tute of Biochemical Plant Pathology is Boehmer, Harvard Medical School in vironment in Common Diseases within with 2.5 million euros each of the among the 31 German prizewinners ESPGHAN Award 2013 for Dr. Eva Boston, and Prof. Dr. Naftali Kaminski, the framework of the program-oriented German Research Foundatiion. of the Chinese Government Award for Reischl: The deputy head of the University of Pittsburgh. funding of the Helmholtz Association. Outstanding Self-financed Students research group “Complex Diseases” MARCH 20th Abroad. of the Research Unit of Molecular JANUARY 14th FEBRUARY 25th Epidemiology receives the award of Improvement of tumor radiotherapy: APRIL 10th the European Society for Paediatric Personalized assessment of the Prof. Dr. Gabriele Multhoff and Dr. Gastroentology, Hepatology and long-term effects of medical radiation Daniela Schilling of the Clinical Co- Plant researcher in the Top 50: Dr. Nutrition, which is endowed with exposure: Dr. Peter Jacob coordinates operation Group “Innate Immunity in Klaus Mayer, head of the Research 30 000 euros. m4 Award goes to Dr. Bernhard Fran- the research program ‘PASSOS’, Tumor Biology” receive a grant of the Unit of Genome and Systems Biology kenberger: For a specific immune- which is financed by the Federal Wilhelm Sander Foundation endowed of Plants, ranks fourth among the MAY 23rd therapy against autoimmune diseases Ministry of Education and Research with 190 000 euros for the develop- most cited scientists in his field in the and leukemia, the team led by Dr. with around three million euros. ment of new treatment approaches. Laborjournal ranking. Prof. Dr. Bernhard Michalke confirmed Bernhard Frankenberger and Prof. Walther and Christine Richtzenhain as FESTEM president: The head of Dr. Dolores Schendel at the Institute Prize for Prof. Dr. Mathias Heiken- the platform “Central Inorganic of Molecular Immunology receives wälder: The junior research group Analysis” at Helmholtz Zentrum the award of the Bavarian Ministry of leader at the Institute of Virology München is elected for the third time Economic Affairs, which is endowed receives the 10 000 euro prize for as President of the Federation of with 500 000 euros. clinical applications in oncology. European Societies on Trace Elements and Minerals (FESTEM). TIMELINE 2013 TIMELINE 2013 14 15
JULY 19th SEPTEMBER 2nd SEPTEMBER 22nd OCTOBER 10th NOVEMBER 29th Timeline 2013 Pin of Honor for Georg Gerl: The The Wilhelm Sander Foundation The Eva and Klaus Grohe Prize goes manager of the Scheyern Exper- supports therapy approach for lung to Dr. Michael Schindler: For his imental Farm in the research tumors: Prof. Dr. Reinhard Zeidler, research in the field of infectious alliance Agroecosystems Munich Research Unit of Gene Vectors, re- diseases, the scientist of the Institute JULY 1st receives the blue Pin of Honor of ceives 120 000 euros for his research of Virology receives the prize of the Technische Universität München. project. Berlin-Brandenburg Academy of Launch of the National Cohort: Prof. Sciences, which is endowed with Dr. Johanna Wanka, Federal Minister JULY 31st OCTOBER 15th 20 000 euros. of Education and Research, presents in Berlin the largest German health Summer campus 2013 begins: 50 chil- Career start: Accompanied by mentors Networking with the world’s top Increased funding for the promo- DECEMBER 3rd study with 200 000 participants. dren of staff participate in two-week of the second year of training, 23 scientists: To kick off the Helmholtz- tion of young scientists: The junior Helmholtz Zentrum München is holiday research program for kids. young people begin their apprentice- Nature Medicine Diabetes Conference research group “Molecular Endocri- Winner of the Ernst Schering Prize building the new central bioreposito- ships in one of eight vocational train- of Helmholtz Zentrum München and nology”, led by Dr. Nina Uhlenhaut, 2014 is announced: Professor Dr. ry on the Neuherberg campus for the AUGUST 1st ing programs at Helmholtz Zentrum the journal Nature Medicine, Prof. Dr. begins work at the Institute for Magdalena Götz, director of the National Cohort. München. Matthias Tschöp presents the Lifetime Diabetes and Obesity. Institute of Stem Cell Research at Official personal dosimeter service Award to Harvard researcher Prof. Dr. Helmholtz Zentrum München and JULY 3rd under new management: The physicist SEPTEMBER 10th C. Ronald Kahn. OCTOBER 17th chair of Physiological Genomics at Markus Figel takes over the man- Ludwig-Maximilians-Universität Health economists to meet in Munich: agement of Germany’s number one ERC Advanced Grant for Prof. Dr. SEPTEMBER 25th German-Chinese cooperation agree- München, receives the prize, which Prof. Dr. Reiner Leidl, Institute of Health personal dosimeter service, which is Magdalena Götz: The European ment signed: The Institute of Virology is endowed with 50 000 euros, for Economics and Health Care Manage- located at Helmholtz Research Council (ERC) supports Best in Big Data: Clueda AG, a spin- at the Bejing Institute of Genomics her research on the molecular basis ment, becomes designated chairman Zentrum München. the research of the director of the off of Helmholtz Zentrum München, cooperates in the investigation of the of brain development. of the German Society for Health Eco- Institute of Stem Cell Research and wins the competition of the journal interactions of the hepatitis B virus nomics and organizer of the 6th Annual AUGUST 5th chair of Physiological Genomics at Computerwoche against 18 compet- with its host. Meeting of the Society in March 2014 at Ludwig-Maximilians-Universität with itors with a computerized analysis Ludwig-Maximilians-Universität. Dissolving protein complexes on a grant amounting to 2.38 million system for stock traders. NOVEMBER 16th the atomic level: At the Institute of euros over five years. JULY 4th Structural Biology under the direction SEPTEMBER 27th Knowledge for all: During the 13th of Dr. Dierk Niessing, a new X-ray SEPTEMBER 16th Munich Science Days the Center Decision-making structures profiled: crystallography platform is available Milestone for process organization: informs the numerous visitors to the The Supervisory Board of Helmholtz for drug development. New member of Leopoldina: Prof. Dr. Nikolaus Blum, CFO, and Dr. Uwe Theresienhöhe about diabetes. Zentrum München adopts the revised Dr. Matthias Tschöp, director of the Bott, head of Human Resources version of the Partnership Agreement AUGUST 7th Institute for Diabetes and Obesity, is Development, inform the staff NOVEMBER 25th and the Rules of Procedure of the accepted into the National Academy about the experience and success Management Board. of Sciences. in implementing a process-oriented Award for new approach to treat organization. leukemia: Seven scientists receive the JULY 10th SEPTEMBER 19th Research Award for Interdisciplinary OCTOBER 1st Cooperation of the Association State Prize for two office administra- Colloquium for Prof. Dr. Rupert of Friends and Sponsors (VdFF) of tors: Paulina Zangler and Christine Lasser: With a two-day farewell Oktoberfest Symposium 2013: In Helmholtz Zentrum München. Zimmermann are honored for conference, the Institute of Biomathe- cooperation with the German Center for outstanding achievement during their matics and Biometry says goodbye to Diabetes Research (DZD), Technische NOVEMBER 29th vocational training with the Bavarian its founding director. Universität München and the Compe- State Prize. Ilse Aigner visits Scheyern: In her tence Network Diabetes Mellitus, the capacity as Federal Minister for SEPTEMBER 20th Institute of Diabetes Research is inviting JULY 16th Nutrition, Agriculture and Consumer participants to a seventh symposium. Protection, the Bavarian politician informs herself at the Experimen- OCTOBER 3rd tal Farm of the Center regarding research on the ecological impacts of Insights of lung research: The third climate change. Munich Lung Conference begins in the Comprehensive Pneumology AUGUST 27th Center with contributions by interna- tional experts. Further expansion of international Clinical Research Award for Prof. Dr. cooperation: Managing Director Dr. Anette-Gabriele Ziegler: The director Helmholtz dissertation prizewinner Alfons Enhsen welcomes the Chinese Science Prize of the city of Freising for of the Institute of Diabetes Research in the research field of Health: Dr. Jan science delegation of the Chinese Dr. Nilima Prakash: The scientist at the receives the Mary Tyler Moore and Krumsiek, Institute of Computational Academy of Sciences during its in- Institute of Developmental Genetics, S. Robert Levine Excellence in Clinical Biology, is one of the winners of the formation visit to Helmholtz Zentrum together with Prof. Dr. Antonio Research Award of the Juvenile Helmholtz Doctoral Award, which München. Simeone, University of Naples, Italy, Diabetes Research Foundation for her was conferred for the first time. receives the Science Prize endowed research into new therapies and pre- with 20 000 euros for their joint ventive measures for type 1 diabetes. research on Parkinson's disease. INTERVIEWS WITH THE MANAGING DIRECTORS INTERVIEWS WITH THE MANAGING DIRECTORS 16 17
2. As a vice president, you are responsible for great potential for technical-medical applications. the Research Field Health within the Helmholtz This might be a bridge between the disciplines Our Concepts and Results Association. How well is our center anchored of engineering and biology, i.e. "bioengineering". thematically in the Helmholtz Association? Wess: The Center’s profile correlates well with the 5. Successful research requires motivated mission of the Helmholtz Association. Our research researchers. What do we need to offer our Are Convincing activities range from basic research to translational scientists to tie them to the Center? research. Our research topics address the major Wess: I see major challenges in the area of challenges of the future. mid-level scientists. Here at the Center there is a group of about 200 people, some in management 3. Health research at Helmholtz Zentrum positions and with fixed-term contracts. These München shall ultimately benefit patients. How are important staff members, without whom our can we strengthen our translational approach in center would not function. It will be crucial to order to translate research results into medical develop new concepts for our personnel and also applications? to find new forms of remuneration, which take Wess: To limit translational research only to trans- performance and function into greater account. lational medicine would be too short-sighted. A solution is still not in the offing, but the topic Of course, as a scientific-technical center we must be addressed and receive more attention. are interested in good collaborations and joint projects with university hospitals because we do 6. What is the greatest challenge facing our not want to have own wards with beds. However, center in the next few years? we are keen that our research results benefit Wess: Our greatest challenge is the renovation patients, as our three translational centers show. of the infrastructure and its further develop- But translation involves much more: It includes ment. Decades of missed opportunities are now early-stage drug discovery projects, the search apparent. A few years ago we began a renovation for new biomarkers or even technical equipment program, using funds of the Center and federal for imaging. Another aspect relates to spin-offs. funds from the economic stimulus program, but Here, with 18 spin-offs that have generated several this was just a drop in the ocean. New laboratory hundred jobs, we are the most successful center in space was leased where we could launch our new the Helmholtz Association. And finally, we always activities, and the new diabetes building supported forget that translation also includes knowledge by Bavaria’s Minister President Seehofer helps a transfer to society, which can hardly be expressed lot. But that is not enough to remain internation- in the usual statistics. This includes insights into ally competitive. Additional resources are urgently new or improved treatment regimens, as well as needed. findings from environmental research. 7. The Center hosts international conferences 4. How are we expanding our endeavors and events more and more often. What is the to promote young scientists, now after the objective? successful positioning of the HELENA graduate Wess: We follow the recommendations of our school? Scientific Advisory Board to increase our interna- Prof. Dr. Günther Wess, CEO, 1. Helmholtz Zentrum München achieved out- demonstrate that this aim has been achieved. We Wess: One of our great strengths is the promotion tional visibility through high-level symposia and Helmholtz Zentrum München, is at standing evaluation results in the expert review received an excellent assessment in the POF III of young scientists. Our HELENA graduate school conferences. Thus, in 2013, the first Helmholtz- the same time vice president and within the framework of program-oriented review. What impressed the reviewers besides the is internationally established with about 330 PhD Nature Medicine Diabetes Conference took place coordinator of the Research Field funding. What makes us the leading center in top achievements of individual scientists was the students, and it has become a brand name among with the Helmholtz Diabetes Lecture by Ronald C. Health in the Helmholtz Associ- the field of environmental health? interaction between various disciplines under graduate schools. A post-doctoral program has Kahn and the presentation of the Helmholtz Young ation. In the interview, Günther Wess: In 2008, under the motto “One 2013”, we one common topic. Furthermore, we have a good just started, for which there is great demand Investigators Diabetes Award. Similarly, the already Wess describes the successes and aimed to become a leading international center in balance between our focus on certain common internationally. And first pilot projects for a well-established “Oktoberfest Symposium” and the strategic developments as well as the field of environmental health within five years. diseases and technology platforms combined with combined MD-PhD program are in the planning international Munich Lung Conference were held. the major challenges the Center The steadily increasing number of high-caliber our expertise in health research and environmental stage that shall give physicians the opportunity This year the Center is participating in the Confer- will face in the next few years. publications and the comments of many international research. With a total of 12 ERC grants, we are the to conduct scientific research. ence of the European Respiratory Society with more reviewers, most recently during the POF III review, most successful center in the Helmholtz Association. A brand new project entitled Pioneer Campus is than 20 000 attendees, which will also take place also being planned. With this program, we want in Munich. Unfortunately, we could not in the past to attract young international “star scientists” to and cannot presently host these important events Munich, where they can carry out interdisciplinary on the Neuherberg campus due to lack of space and research projects under ideal conditions, also with infrastructure. INTERVIEWS WITH THE MANAGING DIRECTORS INTERVIEWS WITH THE MANAGING DIRECTORS 18 19
8. Cooperation is central to successful research. 9. We have focused our research on the major BRIEF PROFILE DR. MARTINA HANSEN How shall we develop our cooperation networks common diseases. What shall we focus on in further, also against the backdrop of new the future? As head of Program Planning forms of cooperation between university and Wess: In recent years, the Research Field Health and Management, Dr. Martina non-university research? has very successfully focused on widespread, Hansen supports the Board of Wess: Technische Universität and Ludwig- common diseases. The founding of the German Directors in the strategic de- velopment and implementation Maximilians-Universität are our most important Centres for Health Research has provided of the scientific programs. Her cooperation partners in Munich, and many joint additional impetus. In the framework of this department is the link between appointments form the backbone of our common strategic orientation, we are ideally positioned management and research; it endeavors. In the framework of the German Cen- with our center motto “Health and Environment”. conducts the scientific con-troll- tres for Health Research and a global orientation It is immediately clear that lung diseases play a ing and provides support in the acquisition of third-party of the Helmholtz Association and our center, we prominent role among the environment-related projects. Science education and have also undertaken joint appointments with diseases. However, it is also increasingly evident training and the promotion of other locations. With the Karlsruhe Institute of that environmental factors such as diet, lack of young scientists are also part Technology (KIT), and the recently founded Berlin physical activity, stress and personal lifestyle of the department’s responsi- Institute of Health (BIH), interesting new models play a very important role in diseases such as bilities. of collaboration between university and non-uni- diabetes. That is why research on these diseases versity research have emerged. With the BIH, the fits perfectly in the Center profile. We were very Federal Government has undertaken a strategic pleased about the suggestion from the experts of step using considerable resources to strengthen the POF III review to strengthen our activities in the research location of Berlin. At the present time, the allergy field. We will be glad to take up this the question cannot be answered whether such suggestion and would like to develop allergy as models are also possible and useful in Munich. the third pillar of the Center alongside diabetes and lung diseases. Here the Center is in a unique 10. As part of the POF reviews, we received then adopted by the Supervisory Board. In the position because the environmental field can recommendations. How shall we implement coming months it will be important to work out the make significant contributions due to its research these? detailed implementation in the topics on a broad in the topic of pollen, analysis or microbiome Wess: The POF program was created in science basis in science, with the support of Program research in the future. And finally, we should not with great support of Program Planning and Man- Planning and Management. It will be important to neglect to mention that we play an important role agement. It must also be implemented in science. develop many good ideas to enhance our leading in the field of virus research in the German Center Only when it is accepted by the broad basis of position internationally. for Infection Research. scientists it can be successfully implemented with The new governance will help us to achieve this. appropriate administrative support. To achieve The Management Committee has a stronger par- this, the Board of Directors has developed a stra- ticipation of scientists than was formerly the case. tegic plan in coordination with the topic speakers Through the participation of the program speaker on the basis of recommendations of the Helmholtz as well as the topic speakers and the respective sci- Senate. It was discussed and endorsed by the entific coordinators, we can discuss scientific issues Scientific Advisory Board. This strategic plan was much more intensively and then make our decisions.
Sonja Opitz, head of Corporate Communications, spoke with Prof. Dr. Günther Wess. INTERVIEWS WITH THE MANAGING DIRECTORS INTERVIEWS WITH THE MANAGING DIRECTORS 20 21
2. Science and administration often feel as if 5. In addition to the introduction of OS and they belong to two different worlds. How can process-oriented organization, the admini- Modern Administration this gap be bridged? stration is continuing to develop its services for Blum: Administration and science are indeed two science. What concrete measures do you have different worlds. Science is judged on academic on your agenda? performance criteria such as the journal impact Blum: Our catalog of measures is derived con- is a Team Sport factor and the acquisition of external funding. sistently from the annual goal for 2014, ranging From the administrative side, however, the from improved information and communication to funding entities expect that the proper execution financial processes and personnel matters. Regarding of administrative processes is ensured. Our task personnel, a policy for fixed-term contracts shall be is to bring these two worlds together and thus to adopted and implemented this year: Employees with create an effective Center. A new approach is the fixed-term contracts shall thus gain more planning establishment of the Department of Operations security. An applicant management system will be and Support, abbreviated OS. With this we wanted introduced to give the Human Resources Depart- to combine the requirements of science and ad- ment stronger support in dealing with applicants ministration as constructively as possible. – that is also a very important point for the public image of the Center. And finally, we will provide the 3. How must we imagine this? institutes and research units with regular budget Blum: Operations and Support has both an inter- information, so that researchers can navigate their preter and a support role. It should translate the resources more easily and efficiently. needs of science into administrative action and at the same time coordinate this action for the 6. Since the beginning of 2014 the new purposes of the scientific projects. OS teams are governance has been in operation at the Center. made up of staff members from science and from To what extent will our core business – the administration. A prime example showing the research – profit from these new structures? enormous added value of support through OS is Blum: The new partnership agreement and the when institutes are founded. New institute directors new governance relate primarily to the external or junior research group leaders must first spend a management of the Center, i.e. the interaction of lot of energy learning how to process procurements, shareholders, the Supervisory Board and the Board what the hiring procedures are and what possi- of Directors. The Public Corporate Governance bilities exist for cooperation. With OS, they have a Codex now also applies to the Center. Despite designated contact person who is familiar with the all the changes, we will continue to intensively processes and knows how to cope with them. implement the internal coordination processes. In the Center, the changed governance will result in 4. What changes can we expect with the intro- noticeably increased action and responsiveness. duction of process-oriented organization? Research will benefit from faster decision making. Blum: Process-oriented organization shall serve Today speed is an absolute competitive advantage to efficiently process the greatly increased num- also in science. ber of standard operations. Each year, we hire approximately 800 employees and process 45 000 Dr. Nikolaus Blum, CFO of the 1. Dr. Blum, science at the Center has developed by around 50 percent. With the German Centres procurements. With process-oriented organiza- Center, served as vice president further and at the same time the complexity of for Health Research, the National Cohort and the tion, we create the conditions to handle these of the Helmholtz Association until the research landscape has increased overall. Initiative and Networking Fund, new financing operations quickly and smoothly with all partic- the end of 2012. In that capacity he What challenges for the administration arise models for science have emerged. This has led to ipating administrative units. This change should advocated more flexibility and a from this fact? a high complexity of the current research struc- not be underestimated!! It is a great challenge, de-bureaucratization of scientific Blum: A major challenge has been the immense tures. The administration has had to cope with because it requires teamwork and the ability to structures. In the interview Dr. growth of the Center. In the last five years the the growth process of the Center and at the same think “outside the box” from all involved. Modern Blum explains his ideas on the role number of employees, the number of procure- time has had to deal with this complexity. administration is a team sport. and development of administrative ments and financial transactions have increased organizational forms at Helmholtz Zentrum München. INTERVIEWS WITH THE MANAGING DIRECTORS INTERVIEWS WITH THE MANAGING DIRECTORS 22 23
7. With compliance management, a new inter- 9. We recruit talent from the outside – how BRIEF PROFILE DR. STEFAN ECHINGER nal structure has been created at the Center. can we promote the potential of staff members What role will it play? at the Center? Dr. Stefan Echinger is head of Blum: Compliance means that an organization Blum: Talent management is one of our most Operations and Support. His complies with existing laws and regulations. That important issues. As a research institution, team supports the Board of is something that is taken for granted. The public our primary role is to promote and train young Directors in the development of scientific organizational and the funding entities expect this from Helmholtz scientists. There are proven instruments for this, units. Operations and Support Zentrum München. However, the spectrum of laws such as the Graduate School HELENA or research is responsible for the imple- and regulations to be observed today is very broad groups with a tenure track option. But of course mentation of new units on and ranges from legal matters, the annual financial the Center must have excellent employees in all an administrative level and statements, the use of research funds, work safety its positions. Therefore, our talent management coordinates the decentralized management of the center and IT security to Good Scientific Practice. Com- is very broad. Our internal qualification program location Grosshadern. pliance management ensures that the framework has grown tremendously in recent years and conditions are known and observed. There are supports the development of the Center with a indications of possible vulnerabilities. Compliance number of targeted measures. The offers of the management is therefore an aid for all managers, Munich Leadership Program, which we organize who must ensure that the existing regulations are for young professionals together with the Centre observed in their area of responsibility. for Science Management Speyer, and the offers of the Helmholtz Academy are open to employees. 8. How can we position ourselves optimally in Human Resources Development at the Center the international competition to attract the best ensures that the strategic objectives for promoting researchers? talent remain in focus. Blum: The attractiveness of the Center for foreign scientists arises primarily from our scientific 10. You successfully advocated more flexi- performance. If this is outstanding, many scientists ble conditions in the recruitment of scientific from other countries will want to come to our personnel in the Helmholtz Association. How center. But of course we must offer the international can we use this new freedom provided by the scientists good conditions and support them in Academic Freedom Act in the best possible way? their integration. Here the administration can make Blum: The Academic Freedom Act has different an important contribution, by providing contact aims. It affects financial leeway, personnel 11. For years Helmholtz Zentrum München has 12. What contribution can highly qualified persons and assistance in finding housing, the questions, construction matters and participation been committed to improving equal opportu- science management make for the international appropriate schools or childcare. In the long term options. One of the new possibilities is to carry nities for women scientists. Has the end of the positioning of German health research and we will also raise the issue of personnel marketing out construction projects up to a volume of five flagpole been reached? in particular research at Helmholtz Zentrum to the international level. Against the background million euros in each center’s own responsibility, Blum: Increasing the percentage of women, München? of demographic change in Germany, we are if a corresponding construction controlling exists. also and especially in leadership positions, is a Blum: In today's complex structures, science is dependent on the recruitment of highly qualified We are currently planning to take advantage of declared goal of Helmholtz Zentrum München. A not possible without good science management. foreign employees. this opportunity. We are also planning further look at the numbers reveals that we have made It is an essential success factor for modern, measures with regard to personnel. good progress. We pay great attention to the interdisciplinary research. Of course, science equal treatment of men and women and use a management has a supporting role and will never variety of funding instruments in order to in- replace the originality and creativity of outstanding crease the proportion of women in management scientists. However, in national and international positions. However, there is certainly potential competition, the successful implementation of for more creative measures. In our view, improv- projects, cooperation in networks and in particu- ing the compatibility of work and family plays lar, the provision of facilities with the necessary a key role. The campus kindergarten is already equipment and consumables are no longer possible functioning very well. Through the Academic without qualified research management. Freedom Act, the Center now has the opportunity Sonja Opitz and Cordula Klemm (from to develop further offers of support from its own right), Corporate Communications, income. We hope that we can make an additional spoke with Dr. Nikolaus Blum. interesting offer for young families still this year. INTERVIEWS WITH THE MANAGING DIRECTORS INTERVIEWS WITH THE MANAGING DIRECTORS 24 25
renovating. These must be decommissioned and 5. Research thrives on the direct exchange deconstructed in order to create new areas for between scientists. What opportunities does Making the Campus construction. We will retain the core of buildings our campus, which is close to the Munich city that can be renovated and expand them for limits, offer for the creation of communicative sustainable use. New construction will take place meeting places? according to modern concepts. Based on the Enhsen: An attractive campus needs facilities for Ready for the Future existing buildings, the contamination situation, an open exchange at all levels in order to ensure energy-technical considerations and the usability that its central mandate – the transfer of knowl- of the building structure, we must develop the edge – is carried out. There is a great need for campus so that we can react flexibly to future appropriate space in the Center. In all major demands for use. remodeling projects and new construction projects, we of course take into consideration the aspects 3. Our center is extensively expanding its diabe- of communication and interaction. The aim is tes research. Two new diabetes institutes and a to promote the exchange of ideas and cooper- new research unit are being established – where ation between the teams. Traffic connections to will the employees/staff members and laborato- the Center also play an important role. Good ries be accommodated? accessibility by public transportation increases the Enhsen: The new Helmholtz Diabetes Campus attractiveness of the Center enormously, especially is in the planning stage. It will encompass two for young scientists and students. In a pilot project laboratory-office complexes for more than 200 with the Munich Public Transport Company, we employees respectively and another building on were able to improve the connections. In the future, the Helmholtz Pioneer Campus for more than however, we want to optimize this further. 150 employees. Over the short term we need to lease office and lab space outside of the campus. 6. The Center wants to expand the field of stem We have already set up two new diabetes cell research. What stands in the way of rapid institutes in Garching and the Comprehensive implementation? Pneumology Center in Grosshadern. Enhsen: Stem cell research at Helmholtz Zentrum München will be located in the future in what 4. The Helmholtz Pioneer Campus shall provide is now the Hämatologikum in Grosshadern. The exceptional young scientists with maximum building needs major renovation in various opportunities for creative research. How will ways, and it will be completely modernized in this be reflected in the architecture? the coming years during ongoing scientific Enhsen: In the Helmholtz Pioneer Campus, ab- operations. Unfortunately, we don’t have any breviated HPC, several scientific disciplines shall alternative space, neither for laboratories nor for work together under one roof. The horizontal infrastructure facilities, so we can’t vacate the and vertical circulation of the building fosters the building completely during renovation. We there- interaction between the different disciplines and fore have to convert and modernize the building scientists. The HPC will be directly connected to floor by floor. the two new diabetes buildings. Thus, the already existing institutes will have direct contact to the 7. The Center competes for the best talent Dr. Alfons Enhsen is Managing 1. Dr. Enhsen, your primary objective in your 2. What is your highest priority for the develop- young scientists in the HPC. The architecture worldwide. How important are state-of-the-art Director for the Scientific-Technical new position is to make the campus fit for the ment of the master plan? will be open and communicative. The young HPC infrastructure and high-end technology in this Infrastructure. In the interview he future. What project is at the top of your agenda? Enhsen: We need to develop the campus so that scientists will conduct their research in flexible, competitive situation? offers an outlook on the intended Enhsen: My objective is to develop and imple- it is flexible and optimally used – now and for large laboratories equipped with state-of-the-art Enhsen: To be internationally competitive and to development of the campus and ment a long-term perspective for the Neuherberg future generations of researchers. This means: technology. achieve top results, both the scientific environment explains his ideas and wishes for campus. This includes the long-term development identification of contaminated sites, renovation, and the working environment with the buildings, the future expansion of the Center. of the master plan and parallel to this, the short- new construction. A number of the buildings and the infrastructure and how well the facilities are term creation and provision of work space, in part of the infrastructure date from the late sixties equipped with modern technology are essential. particular laboratory space. and seventies. Some buildings are no longer worth The campus is optimally positioned in the science region of Munich. Our task is to modernize the campus and design the working environment in an optimal way to ensure efficiency. INTERVIEWS WITH THE MANAGING DIRECTORS INTERVIEWS WITH THE MANAGING DIRECTORS 26 27
8. From whom can we learn here? 9. What role do occupational safety and fire BRIEF PROFILE DR. DRAZENKA SELESI Enhsen: As a rule from the best in the class. We protection play for you? belong to the best in science, but not in infra- Enhsen: Occupational safety affects the health of As coordinator, Dr. Drazenka structure. Science is developing so fast that the each individual employee as well as his or her col- Selesi supports the establish- infrastructure can’t keep pace. This problem can leagues. Nothing should be given higher value. That ment and development of be met to some extent by abandoning the use is why occupational safety measures, including fire the scientific and technical infrastructure. She works in of small-scale lab and office units and instead protection, are non-negotiable. This is a special task a team with the Department creating large, flexibly usable work space. But at the Center, since we have a lot of staff turnover of Scientific Infrastructure, it would be particularly important that we work among young scientists, PhD students and postdocs. Technical Safety and Occupa- on the overall project duration and reduce this Every year there are 500 to 600 new employees at tional Protection headed by Dr. considerably. At the moment we are trapped in the Center, who all must be trained in occupational Alfons Enhsen and the Central Technical Facilities. a situation in which we need eight to nine years safety and introduced to the work environment. The for a new construction project. The private sector responsibility for this lies with the institute direc- manages to complete a project of the same size tors. Our task is to support the institute directors and complexity in just two to two and a half and staff members who have a supervisory role in years. Of course, projects in the private sector this endeavor with our expertise. We need to ensure and the public sector cannot be compared one that all employees are familiar with all safety regu- to one. The federal and state governments must lations, taking into account that people with many be allowed to carry out the test and control different nationalities and native languages work mechanisms with the corresponding approval here. Through annual training modules and regular times, since they are working with tax money. But information, we keep the staff aware of the topic. an ambitious goal would at least be to reduce the Fortunately, in addition to the Department of Infra- current project duration times by half and thus structure and Safety (ISA) which covers all safety to strive for a considerable reduction of the aspects, we have many volunteer safety officers in financial risk. That would definitely be a success. the institutes. We also have many volunteers in the fire department and hope that in the future staff 10. You have been managing director for the scientific-tech- members will support this important task. nical infrastructure in the Center since May 2013. What has impressed you the most? Enhsen: What impresses me is the science. The progress made here at the Center in recent years seeks its comparison in Germany. Science at the Center plays in the top league. That’s why I very much wish to contribute to the development of the infrastructure, in order to meet the expectations placed in us and to achieve our ambitious goals for the future.
Cordula Klemm and Sonja Opitz (from left), Corporate Communications, spoke with Dr. Alfons Enhsen.
Commitment to Promote
IC T R A I
A S NI
B N
G
the Advancement of
Young Scientists
Biology and Diabetes
Helmholtz Zentrum München sets standards in the promotion of young
Diseases of and Metabolic
scientists. The Helmholtz Graduate School Environmental Health (HELENA)
the Lung Diseases
is unique in Europe and is qualifying a new generation of internationally
competitive doctoral students. A newly developed postdoctoral fellowship
program complements the strategic concept of promoting young talent.
The opportunity to be a leader of well-equipped junior research groups
offers young scientists from around the world an ideal career springboard.
Radiation Neuro and Stem
Research Cell Biology
The At the end of 2013, in the third year of its GRADUATE SCHOOL
Helmholtz Graduate School Environmental
Health (HELENA), which was founded in collab existence, the graduate school HELENA had 328 HELENA
oration with Munich’s two elite universities, members. The doctoral students belong to 48
is internationally recognized as a successful different nationalities. Besides Germany and Infection, Immune Systems Biology, model. It offers doctoral students at Helmholtz European countries, particularly China is strongly
Zentrum München an interdisciplinary graduate represented. and Tumor Imaging and
program within eight thematic fields, which Biology Structural Biology
can be tailored to fit each student’s specific The postdoctoral fellowship program at Helm-
interests and needs. holtz Zentrum München was launched in late
2013 with an international call for applicants.
The research focus is on the interaction of Each year, the program recruits ten highly qual- Epidemiology,
individual genetic predisposition, environmental ified postdocs for three years in full scientific
factors and lifestyle and their influence on staff positions in the designated thematic fields Health Economics Ecosystems the pathogenesis of major common diseases. of the Center. The postdoctoral fellows receive and Human Biology The interdisciplinary training and fostering of individual mentoring as well as coaching when Genetics social skills and leadership skills shall prepare applying for external funding. The participants the doctoral students to assume leadership in the program are fully integrated into the L E N positions in science and industry. With the research environment of their respective insti- A O D T I Research School Lung Biology and Disease and tute and are prepared for a successful career in E R A the Research School of Radiation Sciences, S I C academia or industry. H I N the Helmholtz Association supports its own P, M U M A O M research school respectively in the fields of With its junior research group program, N A G E M A N D C lung biology and radiation research under the Helmholtz Zentrum München was able to E N T umbrella of HELENA. recruit young top researchers from around the world. At the end of 2012 the Center had 14 junior research groups; by the end of 2013 this number had risen to 19. Thirteen of the 19 junior research groups are led by women scientists; seven were funded through Starting Grants of the European Research Council. Countries of Origin of
1. EGYPT 13. HAITI 25. CROATIA 37. SWEDEN HELENA 2. ALGERIA 14. INDIA 26. MALAYSIA 38. SERBIA 3. USA 15. IRAQ 27. MACEDONIA 39. SLOVENIA
4. BANGLADESH 16. IRAN 28. MEXICO 40. SPAIN Doctoral Students 5. BOLIVIA 17. ISRAEL 29. NEW ZEALAND 41. SOUTH AFRICA 6. BRAZIL 18. ITALY 30. NETHERLANDS 42. TAIWAN
7. UNITED KINGDOM 19. JAPAN 31. AUSTRIA 43. CZECH REPUBLIC
8. CHINA 20. JORDAN 32. PHILIPPINES 44. TURKEY
9. GERMANY 21. CANADA 33. POLAND 45. UKRAINE
10. ECUADOR 22. KENYA 34. PORTUGAL 46. HUNGARY
11. FRANCE 23. COLOMBIA 35. ROMANIA 47. VENEZUELA
12. GREECE 24. KOREA 36. RUSSIA 48. VIETNAM YOUNG SCIENTISTS YOUNG SCIENTISTS 32 33 Three Years of HELENA
Jan Krumsiek‘s calendar is as full as that of a successful manager: In opportunity to take their courses. “I attended a course in project January he spent a few weeks again at Weill Cornell Medical College management, which was extremely useful,” he said. in New York to advance his scientific work. At the same time, he leads his own research team at the Institute of Computational Biology at The Thesis Committee, an integral feature of HELENA, offered him Helmholtz Zentrum München, supervises four doctoral students and guidance for his dissertation and in general for his doctoral work. does a lot of work at the computer. In addition, he travels to attend It is an advisory body, consisting of the individual’s PhD supervisor, conferences and give lectures. And all this just a year after completing another adviser from the Center and an external expert, which his PhD degree. motivated him and supported him in strategic questions. “Once a year the doctoral student meets with the Committee and discusses the The 30-year-old bioinformatician is one of the top young scientists progress of his/her dissertation,” he said. “That forces you to structure that Helmholtz Zentrum München has promoted in the HELENA your work and helps you stay focused.” In 2013 Krumsiek was awarded Graduate School of Environmental Health. Founded in November the Helmholtz Doctoral Award in the research field Health. 2010, the school is an investment in the future, both for the students and for Helmholtz Zentrum München. “The graduate school provides Krumsiek’s doctoral project involved processing thousands of interdisciplinary education and training in the field of environmental metabolic data sets from a study of the KORA platform (Cooperative health and is an ideal springboard to a successful career,” said Health Research in the Region of Augsburg), which is coordinated Christian Langebartels, director of HELENA and research director for at Helmholtz Zentrum München. The bioinformatician created the field of environmental and radiation research. The spokesperson correlation analyses between the individual values and depicted them of the graduate school is Hans-Werner Mewes, director of the Institute graphically. The result was images of networks which – according to of Bioinformatics and Systems Biology. Krumsiek – “actually correspond to biochemical truths. We verified that. What interested me especially about my topic was that in my Jan Krumsiek had already begun his doctoral work when HELENA research group we spanned the spectrum between biology, medi- was founded. He became a member right from the beginning and, cine, mathematics and informatics. From the depths of biology up to according to him, benefited a lot from the HELENA program. In programming – everything was included.” Interesting and unexpected addition to attending lectures in specialized areas, he took advantage conclusions could be drawn from the data: “We were able to visually of the interdisciplinary courses in presentation training, time and show that men and women differ greatly in their metabolism of amino Photo above: The Neuherberg Doctoral Student Café is an informal meeting place for HELENA members. self-management and courses on the steps involved in the publication acids and fats,” said Krumsiek. “Even differences between depressive Dr. Jin Shao, Sabine Bartel, Dr. Monika Beer, Tao Xu and Nirav Florian Chhabra meet here to discuss process. Since HELENA is also an associate member of the graduate and non-depressive individuals or people with asthma and healthy their work. school of Technische Universität München, he additionally had the people could be determined.” Photo below: Dr. Jan Krumsiek’s dissertation was supervised by Prof. Dr. Fabian Theis (left). The dissertation on the modeling of metabolic networks received doctoral awards from the Center, from the Helmholtz Association and Technische Universität München. Photo left: Jörg Bartel, Michael Laimighofer, Ferdinand Stückler and Kieu Do (from left) work on their doctorate in the team “Systems Metabolomics” led by Dr. Jan Krumsiek at the Institute of Computational Biology. Krumsiek has a three-year Dr. Monika Beer is head of postdoctoral fellowship of the the young scientist develop- Helmholtz Association. At the ment program and scientific same time he is a visiting fellow education and training at at Weill Cornell Medical College Helmholtz Zentrum München. in New York. The biologist is responsible for the HELENA graduate school and the establishment of a new postdoc program at the center. YOUNG SCIENTISTS YOUNG SCIENTISTS 34 35
And the novel graphical representation enabled yet another applica- The concept of the Thesis Committee also ensures that the students “HELENA was the perfect environment Dr. Jin Zhao received her doctor ate with a dissertation on the tion: It provided evidence of metabolic pathways that were not known have mentors and get away from the formerly common individual for my doctorate. Through the HELENA topic of the role of aquaporins before. Through the visualization of the network, researchers are now doctorate. Around 330 graduate students are now taking part in graduate program I received a firm during lateral root formation able to assign metabolites to specific chemical processes. On the one the programs of HELENA, of which 35 percent came from abroad. basis for my research career, in par- in plants. The results of her hand, this is a contribution to basic research. At the same time, this “We have participants from 48 countries,” Beer said. “China is the ticular, how to write a good scientific research were published in approach also provides insights for human medicine. The graphical most strongly represented, with 50 persons. It is also interesting paper.” Nature Cell Biology (see page 98). Since 2013 she is a postdoc network may help to elucidate diseases through blood tests. that more than half of the participants are women.” Dr. Jin Zhao in the Institute of Biochemical Plant Pathology. The geneticist “The success of Jan Krumsiek shows how important it is to provide The preparation for professional life is also an important part of completed her undergraduate interdisciplinary education and training for the doctoral students the HELENA program. “We invite experts to career seminars to studies at the Beijing University. within the framework of HELENA,” said Monika Beer, head of inform the doctoral students about what career options are avail- In 2012 she received a China Scholarship Council Award for Development for Young Scientists in the Department of Program able in the future,” said Monika Beer. Around 40 percent opt for her dissertation at Helmholtz Planning and Management. “They are no longer left to fend for academic careers; the others go into industry or science manage- Zentrum München. themselves; they can seek advice, plan their careers and network ment. “We also want to show the young people career paths that with each other.” are different from the classical paths.” Jan Krumsiek has already decided: He intends to stay at Helmholtz Zentrum München, where he has received a postdoctoral fellowship for three years.
“The Center conducts research on im- Tao Xu came to Munich upon portant topics and provides an excel- recommendation of his Chinese Sabine Bartel is pursuing her supervisor. Jiao Tong University doctorate at the Comprehen- “Due to the integration into HELENA lent scientific infrastructure. I find the Shanghai, where Xu completed sive Pneumology Center with and the graduate research school Lung education and training and scientific a Master’s degree in Biosta- a dissertation on signaling Biology I am linked in a network with supervision in the Helmholtz Graduate tistics and Bioinformatics, pathways in the development other doctoral students. I can partici- School Environmental Health to be collaborates closely with the of asthma. She will finish her pate in conferences in my field, have very enriching. For my scientific work, Research Unit Molecular Epide- doctorate in summer 2014, af- miology at Helmholtz Zentrum ter a research stay at Children’s intensive discussions with visiting the KORA studies platform with its München. For his dissertation, National Medical Center in scientists at the Institute and thus well-studied cohorts is particularly Tao Xu is investigating the Washington, DC, USA, where grow into an international research relevant. If possible, I would like to relationship between metabolic she learned a new method to environment.” remain for some time in Germany profile, cardiovascular diseases isolate gene fragments. In 2010 Sabine Bartel after receiving my PhD degree.” and the influence of smoking. she received her Master’s The results of his research have degree in Molecular Bio- Tao Xu already been published in sev- technology from Technische eral international publications Universität München. (page 92).
Christina Dargel is a member of the Helmholtz Graduate School Nirav Florian Chhabra studied “It was a good idea to come to Helm- “HELENA promotes doctoral stu- Environmental Health and the biotechnology at Manipal holtz Zentrum München. Here I have dents not only academically, but also Medical Graduate Center l of University in Karnataka, India. Technische Universität München. He received his Master’s an inspiring scientific environment. I personally in terms of networking, At the Institute of Virology she degree from the University of participate in the doctoral students’ personal development and career is working on the development Manchester in the UK. Via an initiative DINI, and as HELENA repre- planning. I think that’s something of an immunotherapy for the immunological research project sentative, I am committed to helping special.” treatment of liver cancer. As at the University of Regens- spokesperson for the doctoral Christina Dargel burg, Chhabra subsequently build up the graduate school. And of students, Christina Dargel pro- came to Munich. For his course, I want to support foreign stu- posed and supported an event dissertation at the Institute of dents upon their arrival in Germany format that provides insight Experimental Genetics he is with my experience.” into the day-to-day work of investigating gene functions in Nirav Florian Chhabra scientists in industry. A former the pancreas, which play a role Konrad Adenauer Scholar, she in the pathogenesis of diabetes. studied biology and pharma- ceutical sciences at Munich’s elite universities. She spent one semester at the University of Leiden in conjunction with her Master’s thesis. Junior Research 19 Groups Junior Research Groups
As representative for all research programs, in the following pages we present six junior research groups. JUNIOR RESEARCH GROUPS JUNIOR RESEARCH GROUPS 38 39
BRIEF PROFILE Inconsistencies in scientific models have always fascinated Fabiana Perocchi. “When I DR. FABIANA PEROCCHI discover a puzzle piece that does not seem to fit into the general concepts of a model, Insights into the World I get really excited,” the biologist says. “I keep obsessing about it until I’ve figured out since 2013: what its function is and how it fits into the context of the whole system.” Emmy Noether Junior Research Group Leader at the Institute of Human Genetics, Helmholtz of Mitochondria Perocchi‘s personal puzzle piece is the signaling network of mitochondria. During her time Zentrum München and (since as postdoc at Harvard Medical School she wondered why mitochondria can absorb such 2012) BioSysNet Research a large influx of calcium ions. Perocchi’s curiosity as a researcher was aroused – not least Group Leader at the Gene because the answer to this question might provide relevant insights for medical applica- Center of Ludwig-Maximilians- Cellular “power stations” or mitochondria are Fabiana Perocchi’s passion. The Universität München tions. “Knowledge just for knowledge’s sake is not enough for me,” she stresses. “What’s research of the Rome-born scientist revolves around these energy centers of the important is that knowledge contributes to improving health. 2011-2012: cells: Mitochondria are the center stage of energy metabolism and are involved Senior Postdoctoral Fellow, in many cellular tasks. Mitochondrial dysfunction can lead to a number of Perocchi found that the calcium supply in the mitochondria is crucially involved in cell Centre for Genomic Regulation, signaling. Because this is disturbed in many common diseases, mitochondrial calcium The European Molecular diseases. Fabiana Perocchi investigates the role of mitochondria in cell Biology Laboratory (EMBL), signaling could provide a promising target for new therapy options. “Once we have signaling. Together with her junior research group “Functional Genomics Barcelona, Spain precisely characterized calcium regulated pathways in mitochondria, we can then of Mitochondrial Physiology and Pathophysiology” at the Institute of modulate them and develop therapies for diabetes as well as for neurodegenerative 2008-2011: Human Genetics, she is seeking to elucidate the unsolved mysteries and cardiovascular diseases,” Perocchi says. Her team is currently analyzing the effect Postdoc, Harvard Medical of various active pharmaceutical ingredients on mitochondrial function in order to School and Massachusetts of these organelles. General Hospital, Boston, USA subsequently seek new options for future drugs. 2007: From Harvard, Perocchi was attracted to Helmholtz Zentrum München because of the PhD, European scientific environment. “Munich is a crucible for excellence in the field of mitochondria Molecular Biology Laboratory research. The technological infrastructure and the exchange of ideas with colleagues in Heidelberg related fields have a very positive effect on the advancement of my research,” Perocchi adds. She also greatly appreciates the support of the administrative departments at the Center: “Here I can concentrate completely on my research – I have the feeling that a whole network of departments is behind me.
What Perocchi considers to be most important for her research group is a spirit of cooperation. “Success cannot be achieved if research is conducted in isolation,” she points out.
Everyone in the team must be motivated, curious and independent and at the same time be open to ideas and objections from colleagues. Fabiana Perocchi: “Today research is a dynamic field. Only if you integrate the insights of colleagues into your own considerations can you keep pace with developments and transfer basic research findings into medical applications.”
www.helmholtz-muenchen.de/ Fabiana Perocchi’s research interest is intracellular signal transduction with en/research/research-excellence/ a special focus on mitochondria and their calcium signaling network (image). portraits-of-researchers/ Mitochondria are critically involved in intracellular signaling. dr-fabiana-perocchi JUNIOR RESEARCH GROUPS JUNIOR RESEARCH GROUPS 40 41
BRIEF PROFILE More and more children are being diagnosed with type 1 diabetes. In this autoimmune DR. CAROLIN DANIEL disease the body’s own immune cells gradually destroy the insulin-producing beta Peacekeeping Troops of the cells of the pancreas. The disease could be markedly reduced if Carolin Daniel succeeds since 2012: in applying to humans what she has already achieved on a model organism as a Leader of the junior research Group Immunological postdoc in Boston: By means of an insulin variant she has induced regulatory T cells Tolerance in Type 1 Diabetes at Immune System against to protect the beta cells against an attack of the body’s own immune system, thereby Helmholtz Zentrum München leading to the prevention of type 1 diabetes. 2011: Daniel’s objective is to translate this breakthrough in immunology from the animal model Research awards of the Juvenile Type 1 Diabetes Diabetes Research Foundation to benefit human patients. Together with her team of five, she is seeking to develop a (JDRF) and the Boston Area vaccine that can prevent the onset of type 1 diabetes in childhood. Diabetes Endocrinology Carolin Daniel compares research to studying a mosaic: “If you look at it from Research Center (BADERC) a distance, you see a coherent picture. However, viewed up close, in each The disease has a strong genetic component, which is likely triggered by environmen- tal factors. The main trigger, however, is ultimately a false reaction of the immune 2008-2012: single mosaic piece you will find another hidden mosaic that first must be Postdoc, Dana Farber Cancer system in which the produced immune cells do not distinguish between foreign and elucidated in detail.“ For Carolin Daniel and her junior research group Institute and Harvard Medical endogenous components. Normally in such a case, regulatory T cells move to the scene “Immunological Tolerance in Type 1 Diabetes” at the Institute of Dia- School Boston, fellowship and prevent an attack on the body’s own cells. Daniel therefore refers to the regulatory of the National Academy of betes Research, the overall mosaic is type 1 diabetes, and the special T cells as the “blue helmets, the peacekeeping troops of the immune system”. However, Sciences Leopoldina mosaic piece is the role of regulatory T cells, the so-called peace- in type 1 diabetes, sufficient numbers of these “blue helmets” are lacking to carry out 2008: keeping troops of the body’s own immune system. this function. The beta cells in the pancreas that produce insulin can be destroyed over Fritz Kuelz Prize of the German a period of time by the pathologically activated immune cells. Society for Pharmacology and Toxicology Daniel‘s therapy concept is to strengthen the peacekeeping troops: It is based on converting naive T cells into regulatory T cells with respect to the specific antigen. In 2007-2008: Postdoc, Institute of Pharma- this case, insulin functions as the antigen. That is why researchers first attempted to cology/Immunopharmacology generate regulatory T cells via stimulation with low doses of insulin. This method proved of Goethe University Frankfurt to be inefficient, and the researchers subsequently used higher doses of insulin. Daniel am Main laughs: “That went according to the motto “more helps more”. In fact, through this method diabetes was partially triggered in the model – but regulatory T cells could 2006: Research prize of the Rhine- not be efficiently produced.” Main Society of Gastroenterology
Instead of quantity, Daniel focused on quality. She developed an insulin variant, which 2003-2007: has now been patented, in which a low dose actually leads to the desired result. With Karolinska Institutet Stockholm and Goethe University Frank- her team, the immunologist is now working from an insulin mimetic compound mod- furt am Main, eled after the natural epitope to develop an equivalent vaccine for humans. PhD fellowship of the German Research Foundation, Daniel is convinced that Helmholtz Zentrum München offers her the best conditions to PhD degree (2008) achieve her goal. Here she has access to extensive data and biological samples from children and adults. The material was collected by the director of the Institute of Diabe- tes Research, Anette-Gabriele Ziegler, in part over a period of 20 years. “The data and samples are a gold mine for research and are essential to develop strategies for the prevention of type 1 diabetes and autoimmunity,” Carolin Daniel points out.
Carolin Daniel explores strategies for the prevention of autoimmune diseases such as www.helmholtz-muenchen.de/ type 1 diabetes. A vaccine she developed, which mimics natural insulin, stimulates the en/research/research-excellence/ formation of regulatory T cells (stained blue in the image), which protect the insu- portraits-of-researchers/ lin-producing islet cells (green) against the attack of the immune system. dr-carolin-daniel JUNIOR RESEARCH GROUPS JUNIOR RESEARCH GROUPS 42 43
BRIEF PROFILE Every day in her practical work, it is clear to Stefanie Eyerich how important it is to DR. STEFANIE EYERICH develop new therapy options for inflammatory diseases of the skin. “The patients have Communication Factors a very high level of suffering. My goal is to improve their quality of life,” explains the since 2013: immunologist. Atopic eczema and psoriasis are among the most common diseases of Leader of the junior research group T Cell Biology in Health the skin. In Germany around four million people are affected by atopic eczema, most of and Disease at the Center for Al- under Surveillance them children; an additional three million people have psoriasis. An imbalance in the lergy and Environment (ZAUM)/ immune system underlies both diseases and leads to the appearance of the symptoms. Institute of Allergy Research, T cells, which actually fulfill protective functions in the immune system, play an Technische Universität and Helmholtz Zentrum München Unusual ideas are welcome in Stefanie Eyerich’s team. “They are inspiring and lead important role in the disease process. T cells, also called T lymphocytes, initiate an immune response in the body as soon as they come into contact with substances that to new approaches,” says the leader of the junior research group “T Cell Biology 2013: they recognize as foreign. Certain T lymphocytes remember such a specific immune Robert Koch Postdoctoral in Health and Disease” at the Institute of Allergy Research of Helmholtz Zentrum response and when they encounter the same foreign substance at a later time, they Award for Immunology, München. Stefanie Eyerich also pursues new approaches to help patients trigger a rapid and effective immune response. If the immune system, however, gets ACTERIA Early Career Research out of balance, it classifies the body’s own structures or harmless structures from the Prize for Allergology suffering from atopic eczema and psoriasis. She is exploring the role that environment as dangerous. This leads to an increased release of cytokines, which various T cells play for the barrier function of the skin and is searching 2012: then trigger allergic and inflammatory reactions. for new drug targets. Dr. Ernst Wiethoff Prize Together with her team, Stefanie Eyerich analyzes which specific T cells trigger this 2011: reaction. The main focus is on the communication factors of the T cells, the cytokines. Egon Macher Prize of the Association of Dermatological These interact with epithelial cells in the tissue and instruct them to initiate an in- Research flammatory reaction. The team wants to understand which communication factors are produced so that they can be deactivated with the aid of antibodies. Then, in this case, 2010-2012: the command to trigger an inflammatory reaction would not be given. The onset of the Assistant to the group leader, disease could be prevented, and the patients could be helped effectively. Center for Allergy and Envi- ronment
“For me it was always important to do research that is medically relevant,” the biolo- 2009: gist stresses. The Institute of Allergy Research provides an ideal environment for this: Science Prize of the German Two colleagues in Eyerich‘s team work as doctors in the Clinic for Dermatology and Mycological Society Allergology of Technische Universität München and at the same time conduct research 2009-2010: in the laboratory. “We can analyze T cells directly from patient samples and include Postdoc, Center for Allergy and observations from practice in our research,” says the scientist. Environment
Already during her time as postdoc at Imperial College in London, Eyerich’s primary 2008-2009 : Postdoc, National Heart and research interest was immunology and allergy. One of the most valuable experiences Lung Institute (NHLI), Depart- she gained from her work there in the large laboratory was “the ‘intensively lived’ ment of Allergy and Clinical interdisciplinary communication“. She found these communication structures again at Immunology, Imperial College Helmholtz Zentrum München – another reason “why research here is fun“. From her London, UK staff members she also expects “that they are motivated and enjoy doing their tasks“. 2008: Stefanie Eyerich herself finds it especially motivating to pass on her knowledge to young PhD degree, Technische team members, in order to develop projects together to lead to success. Universität München
Stefanie Eyerich wants to elucidate the immunological causes of inflammatory skin www.helmholtz-muenchen.de/ diseases such as atopic eczema and psoriasis. Her junior research group is focusing on en/research/research-excellence/ the cytokines of specific T cells, which react with skin cells (the image shows a kerati- portraits-of-researchers/ nocyte) and which trigger inflammatory reactions. dr-stefanie-eyerich JUNIOR RESEARCH GROUPS JUNIOR RESEARCH GROUPS 44 45
BRIEF PROFILE Already as a child, Micha Drukker was fascinated with the question of our own creation: DR. MICHA DRUKKER How does a finely coordinated system of organs develop from a single fertilized ovum? Searching for How do molecular interactions between organs mediate development? Trying to find since 2012: the answer to this is what drives Drukker in his research. Leader of the junior research group Human Pluripotent Stem Cell Lineage-Choice Research the Origin The biologist specializes in the study of stem cells. They offer the possibility to study in and the Human Induced Pluri- the lab the development of undifferentiated cells, not yet specified to serve particular potent Stem Cell Unit at the functions, into tissues and thus to come closer to solving the question of how we are Institute of Stem Cell Research, Helmholtz Zentrum München His home is always where top scientists collaborate to discover how stem cells made to become what we are. Drukker uses two cell types for his research: embryonic stem cells and somatic cells. The latter he reprograms back to their original state, so develop into the specialized cell types that our body is consisted of. Micha 2010-2012: that they, too, are pluripotent. Then by applying signals and factors they can be in- Research associate, Drukker already conducted research on this topic at The Hebrew University structed to develop into any cell type. Using embryonic stem cells, the scientist defines Stanford University, USA in Israel and at Stanford University in the U.S. Since 2012 he has headed the precisely when pluripotent cells develop into specialized cells and which mechanisms and molecules are responsible for this. “When we have analyzed these processes, we 2005-2010: junior research group “Human Pluripotent Stem Cell Lineage Choice” Postdoctoral fellowship, can open up a wide area of medical applications,” says Drukker. at the Institute of Stem Cell Research at Helmholtz Zentrum München – Stanford University, USA
and feels as if he has arrived home. “I was already acquainted At Stanford University he developed a technique with which tissue progenitor cells can 2005: with my colleagues and knew that this is an ideal environment be isolated very efficiently from mixed cultures of differentiating stem cells. Using this PhD degree, The Hebrew to study fundamental questions and translate the findings for technique at Helmholtz Zentrum München, he is now focusing on purifying tissue- University, Israel studying development of multifactorial diseases.” regenerating cells from pluripotent stem cells, including beta cells for the therapy of type 1 diabetes patients. ” My goal is to replace functionless or inefficiently working cells in diabetes or Parkinson patients with functioning cells,” the scientist explains.
Using the second cell type, the reprogrammed skin cells, Drukker wants to find out how normal pluripotent cells differ from those of the patient samples: “Reprogrammed cells are well suited to study in vitro where the switches are set for the development of multifactorial diseases such as diabetes or neurodegenerative diseases.“
The research group leader also offers expertise and techniques to other scientists. He is convinced that research today can only succeed when the experts of various specialized areas work together in synergy. “The days of the generalists are over,” he stresses. That is why he especially appreciates the fact that a broad scientific spectrum can be encountered directly at the Center. “I work here like in a kibbutz: My colleagues and I are a great community, who are together attempting to understand the question of life emergence. Everyone is at the top of his or her field. That inspires me,” says Drukker.
The aim of Micha Drukker is to provide cures for diseases by means of induced pluri- www.helmholtz-muenchen.de/ potent stem cells. His team reprograms cells from patients affected with diabetes and en/research/research-excellence/ Parkinson’s disease (image) with the aid of mRNA molecules encoding specialized sets portraits-of-researchers/ of transcription factors . dr-micha-drukker JUNIOR RESEARCH GROUPS JUNIOR RESEARCH GROUPS 46 47
BRIEF PROFILE During his studies, Tobias Madl was also interested in physics, computer science and DR. TOBIAS MADL history. Whether in historical archives or in the chemistry lab – the main objective for Proteins under the the future chemist was to break new ground and to close knowledge gaps. “To have since 2012: new things to discover and to thus benefit mankind, that’s what drives me forward,” Emmy Noether Junior Research Group Leader at Helmholtz he says, describing his motivation. For him it is important to have the freedom to look Zentrum München and Junior Hammer right and left. “That is not a waste of time, but rather serves a purpose.” Fellow at Technische Universität München; APART fellow at the Madl‘s Team is based at the Institute of Structural Biology (STB) and the Bavarian University of Utrecht and University of Graz Proteins are the building blocks of life. If something goes wrong during their pro- NMR Center, which is run jointly by Technische Universität München and Helmholtz Zentrum München. The group maintains close cooperation on various levels. In col- duction, diseases such as diabetes, cancer and neurodegenerative changes can 2012: laboration with the Institute of Molecular Cancer Research at the University of Utrecht, Science Prize of the be the result. Using state-of-the-art equipment, Tobias Madl and his ten-member the researchers explore how signal transductions are influenced by defective proteins Austrian Chemical Society team of the junior research group “Structural Biology of Signal Transduction” and by the environment, e.g. oxidative stress, thus leading to the development of cancer. Together with the Ludwig-Maximilians-Universität München and the German 2010–2011: are searching for the molecular causes of such production errors. Postdoc, University of Utrecht Center for Neurodegenerative Diseases, the role of RNA-binding proteins is analyzed in the regulation of signal transduction. And finally, with partners from the University 2008: of Tübingen, the group checks whether the molecular and cell biological findings are Schrödinger Fellowship of the confirmed in clinical studies. “These collaborations make it possible to bridge the gap Austrian Fund to Promote between the disease and the molecular causes," says Madl, describing the synergy. Scientific Research 2007–2010: For the first step, the characterization of the proteins, the group in the Bavarian NMR Postdoc, Institute of Center has access to state-of-the-art NMR spectroscopy equipment. Using these devices, Structural Biology, Helmholtz Madl analyzes the spatial structure and the interaction of the protein areas. To explain Zentrum München and Tech the highly complex method, the chemist illustrates it with a comparison: “We hit with nische Universität München, EMBO Fellowship a hammer on the atoms in the molecules and listen as they scream. From the data on the location and strength of the scream we can derive the spatial structures of the 2007: proteins and investigate interactions between the protein areas.” PhD degree, postdoc University of Graz To obtain information regarding the form of the biomolecules complementary to the NMR spectroscopic data, the team uses the SAXS system to measure the small angle X-ray scattering. Using a program Madl developed, these data are combined with the NMR data to obtain the structural and dynamic characteristics of the target protein. Step by step, the researchers are now beginning to study the individual elements in detail. Their aim is to find out which structures are responsible for the development of diseases and which could serve as potential drug targets.
To elucidate the interactions between proteins and other cell organelles, different methods must be combined. “I am therefore glad that at Helmholtz Zentrum München there is a great concentration of outstanding biological research. Here I can also study how environmental factors regulate proteins and whether they are responsible for dysregulations“, says Madl. In his opinion, scientific exchange with other research groups is essential to answer these challenging questions. Besides scientific expertise, the research group leader therefore places emphasis on social competence: “We are happy to measure ourselves against external competition. But within the team there is no place for this – we all are dependent on each other and benefit from each other.”
www.helmholtz-muenchen.de/ Tobias Madl investigates the spatial structures of proteins that transmit signals between en/research/research-excellence/ cells. He wants to find out how defective proteins transmit signals between cells (in the portraits-of-researchers/ image transportin), leading to the development of diseases. dr-tobias-madl JUNIOR RESEARCH GROUPS JUNIOR RESEARCH GROUPS 48 49
BRIEF PROFILE Corina Vlot-Schuster‘s area of research is a special form of plant defense called systemic DR. CORINA VLOT-SCHUSTER acquired resistance (SAR). Although plants do not produce any antibodies, they can react Signals for the to locally limited attacks of pathogens with a kind of long-term immunity: Cells die off since 2009: around the affected area and prevent the spread of the infection. At the same time signal Leader of the junior research group Inducible Resistance substances are emitted that lead to an increase of resistance in the entire plant and Signaling, Institute of Bio Protection of Plants protect against a wide range of pathogens. chemical Plant Pathology, Helmholtz Zentrum München This mechanism has been extensively studied in thale cress. Corina Vlot-Schuster showed that SAR also protects barley from invading pests such as bacteria. Together 2007-2009: Corina Vlot-Schuster discovered her fascination with plant immune defense early Marie Curie/EMBO Fellow, with her six-member team, the Dutch-born scientist wants to characterize the involved in her career. During her time at the Boyce Thompson Institute in the U.S. and at Max Planck Institute of signaling molecules in this agriculturally important grain plant and to protect this and Plant Breeding Research, the Max Planck Institute for Plant Breeding Research in Cologne, she explored other crops against pests in the future with the plant’s natural defense substances. Cologne systemic acquired resistance in Arabidopsis thaliana, thale cress. This model “SAR is very attractive for use in crop agriculture. Since the plant hardly uses resources for this kind of defense, the crop yield is not adversely affected,” explains Vlot-Schuster. 2003-2006: plant is also well established at Helmholtz Zentrum München. When she Postdoc, Boyce Thompson was offered the opportunity to lead the junior research group “Inducible Institute of Plant Research, To identify key molecules that are responsible for triggering the mechanism, the plant Ithaca, USA Resistance Signaling” at the Institute of Biochemical Plant Pathology, physiologist is supported by experts from other fields. For the characterization of the Vlot-Schuster did not hesitate to accept. signal molecules in barley, she benefited from the work of bioinformaticians in the 2003: Research Unit Genome and Systems Biology of Plants: In 2012 they deciphered the entire PhD degree, Leiden University, The Netherlands barley genome. At Helmholtz Zentrum München Vlot-Schuster conducts her research quasi next door to these colleagues: “We are on equal footing, and our collaboration is uncomplicated. We work hand in hand and try to solve problems together.”
This type of collaboration also has a profound effect on her team. Vlot-Schuster selected her staff based on scientific criteria, but also on their social competence. “We discuss all decisions together,” she says. She expects from her team members that they assume responsibility and work independently. Vlot-Schuster: “If you want to be successful in implementing your projects later on, these are core competences.”
The biologist works in a challenging academic environment. “It has become more difficult to publish results in high-quality, prestigious journals“, she observed – a development that she finds also has positive aspects: “You set your own bar higher and higher, and this increases the quality of the research.”
In addition to academic success, however, Corina Vlot-Schuster is also pursuing another objective: “It has always been important to me that my research can also be applied to protect the environment and to produce potentially healthier foods.”
Corina Vlot-Schuster wants to use the natural defense mechanisms of plants for the www.helmholtz-muenchen.de/ environmentally friendly production of food crops. Her focus is on signal substances en/research/research-excellence/ that are involved in systemic acquired resistance (SAR), which she explores in the portraits-of-researchers/ model plant Arabidopsis thaliana (image) and in barley. dr-corina-vlot-schuster Conducting Research POF SPEAKERS: Program-Oriented GenCoDe Program within Strategic Funding Prof. Dr. Wolfgang Wurst wurst@ helmholtz-muenchen.de T 089 3187 4111 Programs 1 Prof. Dr. Martin Hrabe de Angelis hrabe@ helmholtz-muenchen.de Research activities at Helmholtz Zentrum München are linked thematically GEnCoDe TE T 089 3187 3302 and with regard to content through strategic programs of the Helmholtz Genes and Environment Terrestrial 2 Prof. Dr. Matthias Tschöp Association and are financed through program-oriented funding (POF). in Common Diseases Environment matthias.tschoep@ helmholtz-muenchen.de Complex questions and problems relevant to science, society and the T 089 3187 2103 economy can thus be explored across institutional and disciplinary borders. 3 Prof. Dr. Oliver Eickelberg oliver.eickelberg@ TOPICS helmholtz-muenchen.de T 089 3187 4666 Systemic analysis of genetic 1 and environmental factors that 4 Prof. Dr. Magdalena Götz impact health magdalena.goetz@ helmholtz-muenchen.de Within the framework of program-oriented Besides Helmholtz Zentrum München, which T 089 3187 3750 funding, Helmholtz Zentrum München is coordinates GEnCoDe, the Helmholtz Centre for 2 Diabetes: pathophysiology, 2 Sustainable integrated into the two research fields: “Health” Environmental Research (UFZ), Leipzig, has a prevention and therapy plant production 5 Prof. Dr. Vasilis and “Earth and Environment”. Following the seven percent stake in the project. The scientific Ntziachristos successful review in the field of Health, the content of the program is divided into five topics. Chronic diseases of the lung Sustainable v.ntziachristos@ 3 3 helmholtz-muenchen.de Center is continuing to focus on the investigation and allergies water management T 089 3187 3852 of major common diseases. In the third POF Helmholtz Zentrum München concentrates its phase beginning in 2014, the Center is pooling environmental research in the program “Terres- Mechanisms of genetic and TE Program its resources in the health program GEnCoDe trial Environment” (TE). The Center focuses on 4 environmental influences on 2 Prof. Dr. Jörg Durner (Genes and Environment in Common Diseases). the areas of plant defense and stress resistance, health and disease durner@ In the field of Earth and Environment, the Center water quality, control of ecosystems and the helmholtz-muenchen.de is conducting research in the program Terrestrial prevention of environment-related diseases. 5 New technologies for 5 Terrestrial systems: from the T 089 3187 3434 Environment (TE). Helmholtz Zentrum München collaborates close- biomedical discoveries observation to the prediction ly with the Helmholtz Centre for Environmental 3 Prof. Dr. Rainer Meckenstock With the program “Genes and Environment Research (UFZ), Leipzig, which coordinates the rainer.meckenstock@ in Common Diseases”(GEnCoDe), Helmholtz program, and Forschungszentrum Jülich. With a helmholtz-muenchen.de Zentrum München is assuming a leading role in program share of 23 percent, Helmholtz Zentrum T 089 3187 2560 innovative health research. The aim of GEnCoDe München is engaged in three of the five topics. CROSS-DISCIPLINARY ACTIVITIES is to elucidate gene-environment interactions 5 Dr. Eckart Priesack priesack@ and their significance in the pathogenesis of In the research area Health, Helmholtz Zentrum Personalized Medicine Bioeconomics: helmholtz-muenchen.de common diseases, in particular diabetes, lung München is involved in all cross-disciplinary climate research, water T 089 3187 3354 diseases and allergies. The GEnCoDe program is activities. Helmholtz Zentrum München and linked beyond the borders of various disciplines. four additional Helmholtz health centers have It brings together the successful predecessor joined together in the association Personalized programs “Environmental Health” and “Systemic Medicine. In the research field Earth and the Strategic Partnerships Analysis of Multifactorial Diseases” and generates Environment the Center participates in the Allergy, Microbiome and Climate Research additional synergies for the elucidation of the cross-disciplinary topics and associations underlying mechanisms of major common dis- Bioeconomics, Climate Research and Water. eases and their prevention, diagnosis and therapy. 2240publications in 2012 and 2013 RESEARCH HIGHLIGHTS
From the publications of the last two years we present 34 scientific highlights. HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 54 55
BRIEF PROFILE DR. TIMO MÜLLER Leader of the research group Brain Signal Regulates Molecular Pharmacology at the Institute for Diabetes and Obesity, Helmholtz Zentrum München Body Weight 2011: Outstanding Young Investigator Award of the American Society for Clinical Scientists of the Institute for Diabetes and Obesity, an activation or inhibition of neuronal signaling Fasting Ghrelin Investigation/ American in collaboration with partners from the Charité mechanisms that control the sensation for hunger Academy of Pediatrics 2008–2011: Postdoc at the – Universitätsmedizin in Berlin, have discovered and satiety. One of these signals is the hormone Metabolic Diseases Institute, that a receptor in the brain whose function was ghrelin which, produced in the stomach, reaches Ghsr Ghsr University of Cincinnati, largely unknown until now is involved in the the brain via the bloodstream. In the brain, Gpr83 Ohio, USA regulation of body weight. As the research group ghrelin activates regulatory circuits that control 2005-2008: PhD at the University of Duisburg-Essen led by Timo Müller has shown for the first time, food intake. As the scientists found out, Gpr83 cell membrane the molecule Gpr83 (G protein-coupled receptor affects energy metabolism both via direct inter- 83) plays a crucial role in the regulation of energy action with the ghrelin signaling pathway as well balance. Thus, mice with a loss of function of this as via not yet identified ghrelin-independent receptor are protected from obesity and diabetes, signaling mechanisms. In further studies, specific
even after being fed a high-fat diet. binding partners of Gpr83 shall be identified. The regulation of body weight is a complex The researchers thus hope to obtain new process in which organs such as the gastrointes- strategies for the treatment of obesity and tinal (GI) tract and adipose tissue are in constant diabetes. If blocking Gpr83 proves to be a safe, cross-talk with the brain about the current energy targeted approach, this could lead to new
status. The brain responds to the GI signals with pharmacotherapies to treat metabolic diseases. Food intake
Ghrelin
Gpr83/Ghsr heterodimer
The Gpr83 receptor expressed in the brain plays a crucial role in the cell membrane regulation of body weight. The new finding that Gpr83influences body weight through an interaction with the appetite-stimulating Original Publication: hormone ghrelin, among other means, constitutes an important Timo D. Müller et al.: The contribution to the elucidation of the signaling networks involved in Orphan Receptor Gpr83 Regu- the control of body fat and glucose metabolism. lates Systemic Energy Metabo- lism via Ghrelin-Dependent and Fasting reduces the expression of the brain receptor Gpr83 in the hypothalamus. Its dimerization Ghrelin-Independent Mecha with the ghrelin receptor Ghsr is thereby reduced, and ghrelin can stimulate food intake by nisms. Nature Communications binding to Ghsr. Food intake increases the expression of Gpr83. More Gpr83-Ghsr heterodimers 4 (2013) 1968 | doi: 10.1038/ are formed, and the ability of ghrelin to activate the ghrelin receptor is reduced. ncomms2968 Ghrelin is a hormone primarily produced in the gastric mucosa that has an appetite-stimulating effect. In the fasting state, ghrelin levels Further authors from rise in the blood and decrease again after each meal. In addition to Helmholtz Zentrum München: the regulation of food intake, ghrelin has a number of other effects Chun-Xia Yi, Carola W. Meyer, such as the stimulation of growth hormone secretion. Brian Finan, Kerstin Stemmer, Paul T. Pfluger, Matthias H. Tschöp – Institute for Diabetes and Obesity Susanna Hofmann – Institute of Diabetes and Regeneration Research HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 56 57
BRIEF PROFILE BRIEF PROFILE DR. BRIAN FINAN DR. KERSTIN STEMMER Leader of the research group Hormones against Hormone Duo Promotes Leader of the research group Drug Discovery at the Institute Metabolism and Cancer at the for Diabetes and Obesity, Institute for Diabetes and Helmholtz Zentrum München Obesity, Helmholtz Zentrum Metabolic Syndrome Loss of Fat Reserves München 2012-2013: Postdoc, Institute for Diabetes and Obesity, 2010-2012: Guest scientist at Helmholtz Zentrum München the Woods/Seeley Obesity 2006-2012: Scientific staff Scientists of the Institute for Diabetes and tumor risk. The trick is that the gut hormone The interaction of the two hormones gluca- decreasing cholesterol levels. At the same time Research Laboratory, Metabolic member, Indiana University, Diseases Institute, University of Obesity together with U.S. cooperation partners only delivers the conjugated estrogen to certain gon and fibroblast growth factor 21 (FGF21) there was a significant increase in the hormone Bloomington, USA Cincinnati, USA 2011: PhD degree have succeeded in using tissue-specific drugs cell types. On the basis of GLP-1, drugs have has a decisive impact on lipid metabolism and FGF21. This effect could be detected not only 2008-2010: Deputy leader of to target metabolic syndrome, a pre-existing been developed that are already approved for body weight. Their coordinated action leads in mice but also in humans. If the mice lacked the research group Human and condition of type 2 diabetes. They selectively the treatment of type 2 diabetes. In the animal to decreased food intake and increased fat FGF21 due to a genetic defect (FGF21 knock-out Environmental Toxicology, directed estrogen to specific cell types by model, both in the treatment of obesity as well burning, as scientists of the Institute for Diabetes mice), glucagon lost its positive properties on University of Konstanz 2008: PhD degree binding it to the gut hormone GLP-1 (glucagon- as type 2 diabetes, the novel conjugate shows a and Obesity in cooperation with the Metabolic metabolism. From this the scientists infer that 2002-2003: Scientific staff like-peptide 1), thereby causing the symptoms significantly better effect than GLP-1 alone. Diseases Institute of the University of Cincinnati, FGF21 is essential for the effects mediated by member, Max Delbrück of metabolic syndrome to diminish. Metabolic syndrome, obesity and type 2 diabetes USA, discovered. The two neurotransmitters are glucagon on fat burning and cholesterol levels. Center for Molecular If the hormone estrogen is chemically conju- are increasing in Germany and worldwide in thus considered to be promising target struc- The results support earlier work by the team Medicine Berlin and German gated to the gut hormone GLP-1, the estrogen epidemic proportions, thus presenting major tures for treating obesity and type 2 diabetes. according to which fusion hormones from Institute of Human Nutrition, Potsdam-Rehbrücke merely passes into the GLP-1 target cells, but challenges to the health system. Therefore new As “hunger hormone”, glucagon mediates a glucagon and glucagon-like peptides (e.g. gluca- not into estrogen-sensitive organs such as the and effective therapy concepts with minimal side reduction of the energy reserves of the body. For gon-like-peptide 1, GLP-1) have a significant uterus. With this novel conjugate between a effects are urgently needed, especially for these the first time, the scientists found that the direct potential for the treatment of obesity and diabe- peptide and steroid hormone the scientists forms of the disease. The conjugate approach interaction with the neurotransmitter FGF21 is tes. Until now, however, the signaling pathway showed in the animal model that estrogen can may represent a completely new treatment con- required for this effect. The team led by Kerstin was unknown through which glucagon reduces maximize the effect of GLP-1 in reducing levels cept which may similarly be applied to a number Stemmer and Matthias Tschöp studied the fat reserves. In further studies the details of the of blood glucose and in loss of body fat, but for of other diseases that may likewise be influenced long-term effect of glucagon in a mouse model hormonal interaction of glucagon and FGF21 the first time without the negative side effects by steroid hormones. and showed that this effect is characterized by shall be explored to examine potential applica- of estrogen on the uterus and without elevated decreased food intake, increased fat burning and tions for the treatment of metabolic diseases.
By conjugating the gut hormone GLP-1 with estrogen, scientists Due to the coordinated action of the two hormones glucagon and Original Publication: succeeded in the animal model to direct this peptide-steroid conjugate fibroblast growth factor 21 (FGF21), there is a decreased food Brian Finan et al.: Targeted to specific tissues. There it caused a reduction of the symptoms of intake and increased fat burning. Therefore, the two substances are Estrogen Delivery Reverses the metabolic syndrome without triggering the negative side effects of considered to be potential targets for the treatment of metabolic Metabolic Syndrome. Nature Medicine 18 (2012) 1847-56 | estrogen. diseases such as obesity and type 2 diabetes. Original Publication: doi: 10.1038/nm.3009 Kirk M. Habegger et al.: Fibroblast Growth Factor 21 Mediates Specific Glucagon Further authors from Actions. The metabolic syndrome describes the simultaneous occurrence The main task of the peptide hormone glucagon, which is formed in Helmholtz Zentrum München: Diabetes 62 (2013) 1453-1463 | Kerstin Stemmer, Timo D. of multiple disease symptoms such as obesity, elevated fasting glucose the alpha islet cells of the pancreas, is to increase the blood glucose doi: 10.2337/db12-1116 Müller, Chun-Xia Yi, Sonja C. and blood lipid levels, and high blood pressure. level. When blood glucose levels drop, glucagon is released into the Schriever, Cristina García- This combination increases the risk of atherosclerosis, diabetes and blood stream and is the counter-regulatory hormone opposing insulin Cáceres, Dhiraj G. Kabra, Paul heart disease. action in glucose and lipid metabolism. Further authors from Pfluger, Matthias H. Tschöp – Helmholtz Zentrum München: Institute for Diabetes and Timo Müller, Paul T. Pfluger, Obesity Matthias H. Tschöp – Institute Wolfgang Hans, Martin Irmler, for Diabetes and Obesity Johannes Beckers, Martin Susanna Hofmann – Institute of Hrabe de Angelis – Institute of Diabetes and Regeneration Experimental Genetics Research HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 58 59
BRIEF PROFILE BRIEF PROFILE PROF. DR. MATTHIAS TSCHÖP DR. MARTIN JASTROCH Scientific speaker of the Efficacy Prognosis Evolution of Leader of the research group Helmholtz Diabetes Center Mitochondrial Biology at the (HDC) and director of the Institute for Diabetes and Institute for Diabetes and Obesity, Helmholtz Zentrum Obesity at Helmholtz Zentrum for Gastric Bypass Energy Metabolism München München, chair of Metabolic Diseases at Technische 2011: Research Recognition Universität München Award of the American (Alexander von Humboldt Gastric bypass is one of the most frequently per- in the blood rises significantly. GLP-1 increases Scientists of the Institute for Diabetes and Obe- primitive thermoregulatory features as they do Physiological Society professorship) 2009–2011: Research formed surgical procedures used to treat obesity insulin secretion and contributes to improved sity, together with colleagues of the University not maintain a constant high body temperature. scholarship of the German since 2012: Adjunct professor, and leads to a rapid loss of body weight in most blood glucose levels and blood lipids. As the sci- of Marburg and the Medical Research Council, However, they have brown adipose tissue and Research Foundation Yale University (USA) patients. In addition, the surgical intervention entists led by Tschöp and Habegger showed, the Cambridge, UK have found that thermogenesis active uncoupling protein 1 (UCP1), the latter 2008–2011: Postdoc, Buck 2003–2011: Professor of induces an improved glucose metabolism – efficacy of the secreted GLP-1 on blood glucose in the brown adipose tissue of mammals is an being essential for burning fats. The scientists Institute for Research on Aging, Endocrinology at the Institute even before the weight loss. These metabolic levels varies: the higher the sensitivity of the rats ancient mechanism. conclude that fat burning is a physiological Novato, CA, USA of Metabolic Diseases and 2008: Best PhD thesis award in scientific director of the improvements, however, vary considerably from in the animal model to GLP-1, the more effective Brown adipose tissue serves mammals in the process that developed early in evolution, inde- biology at the University of Diabetes and Obesity Center at patient to patient. the gastric bypass. generation of heat by burning fat reserves. The pendent of sustained body temperatures. The Marburg the University of Cincinnati A hormone test could possibly predict to what GLP-1 sensitivity could thus serve as a new pre- ability to maintain high body temperatures with- study allows a new view on energy metabolism 2007–2008: Scientific staff 2002–2003: Research group extent a gastric bypass would improve metab- dictive biomarker for personalized therapeutic out shivering – i.e. without the physical work of with regard to evolution and the functionality member, University of Marburg leader at the German Institute olism. Scientists led by Matthias Tschöp of the approaches for type 2 diabetes and obesity. muscles – has played an important evolutionary of brown adipose tissue. The scientists intend 2007: PhD degree, University of of Human Nutrition Potsdam- Marburg Rehbrücke (DIfE) Institute for Diabetes and Obesity at Helmholtz If the results are confirmed in the patient trials, role for the colonization of cold habitats but to broaden technological advances of this study 2005: Young investigator 1999–2002: Postdoc in an Zentrum München and Kirk Habegger at the the hormone response could be tested prior presumably also for reproduction. The team to characterize brown adipose tissue to identify competition award “Frontiers international pharmaceutical Metabolic Disease Institute of the University of to a planned gastric bypass to determine to led by Martin Jastroch and Carola Meyer of the novel activators of fat burning. Of particular in- in Thermoregulation” company in the U.S. Cincinnati discovered this using an animal model. what extent the patient would benefit from the Institute for Diabetes and Obesity was able to terest are the uncoupling proteins such as UCP1, After gastric bypass surgery the concentration of surgical procedure. demonstrate that fully functional brown adipose which are crucially involved in the balance of BRIEF PROFILE the gut hormone GLP-1 (glucagon-like-peptide 1) tissue developed at an early stage in mam- energy metabolism. Translating the fundamental DR. CAROLA W. MEYER malian evolution. To this end, the researchers findings on brown adipose tissue function, their studied Madagascan Lesser hedgehog tenrecs studies will assist in developing new therapeutic Leader of the research group (Echinops telfairi), a species that diverged from concepts to increase fat burning , thus reducing Metabolic Physiology at the modern mammals long ago. Tenrecs display excess fat reserves, e.g. in obesity. Institute for Diabetes and Obesity, Helmholtz Zentrum München
2011: Adjunct professor Zoology/Animal Physiology, University of Marburg 2005–2010: Scientific staff member and research group The response to the hormone GLP-1 (glucagon-like-peptide 1), which is Lesser hedgehog tenrecs – higher mammals that do not have con- leader in Zoology/Animal Phys- formed in the gastrointestinal tract, can predict the efficacy of a gastric stant body temperature – allowed the scientists to conclude that fat iology, University of Marburg bypass. GLP-1 sensitivity could therefore be used as a new biomarker burning is a physiological process that was developed early in mam- 2005: PhD degree in Zoology/Animal Physiology, for personalized therapeutic approaches in patients with type 2 malian evolution, possibly prior to sustained high body temperature. University of Marburg diabetes and obesity. Original Publication: Kirk M. Habegger et al: GLP-1R Original Publication: Responsiveness Predicts Rebecca Oelkrug et al.: Brown Individual Fat in a Protoendothermic In a , only a small remnant of the stomach that is a special form of fat tissue, whose cells Gastric Bypass Efficacy gastric bypass Brown adipose tissue Mammal Fuels Eutherian on Glucose Tolerance in Rats. holds about 15 ml remains. Furthermore, the upper small intestine are able to generate heat by oxidation of fatty acids (thermogenesis). Evolution. Diabetes (2013) Nov 1. [Epub is bypassed. The digestive juices are introduced into the deeper This occurs in numerous mitochondria, which are also responsible for Nature Communications ahead of print] | doi: 10.2337/ portions of the intestine where digestion begins. As a result, only the yellow-brownish color of the tissue. 4 (2013) 2140 | doi: 10.1038/ db13-0511 part of the food is absorbed. The undigested food is conveyed into ncomms3140 the large intestine. Further authors from Further authors from Helmholtz Zentrum München: Helmholtz Zentrum München: Timo D. Müller, Paul T. Pfluger – Maria Kutschke, Saskia Müller, Institute for Diabetes and Matthias H. Tschöp – Institute Obesity for Diabetes and Obesity HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 60 61
BRIEF PROFILE DR. RUI WANG-SATTLER Research group leader, Biomarkers of Research Unit Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München Pre-diabetes 2007-2011: Senior scientist, Institute of Epidemiology, Helmholtz Zentrum München Pre-diabetes is the early form of type 2 and from partner institutes in the German Metabolite 2010: Paula and Richard von Acetyl Carnitine C2 Glycine LPC (18:2) diabetes, one of the most important common Center for Diabetes Research identified three Hertwig Prize for Interdis ciplinary Research diseases. Between about eight to ten percent candidate biomarkers for pre-diabetes, two 2000-2007: Postdoc, of the German population suffers from this of which predicted the risk of the disease in Enzyme European Molecular Biology disease, and its incidence is increasing rapidly. individuals. Using a metabolomics approach, Laboratory (EMBL) In the pre-diabetic stage, the further develop- they quantified 140 metabolites in 4297 serum ment of the disease can be largely prevented, samples of the population-based Cooperative CAC CrAT ALAS-H cPLA2 Pathway-related for example by dietary changes or increased Health Research in the Region of Augsburg protein physical activity. Up to now, however, no spe- (KORA) cohort. The results were independently cific biomarkers have been available to reliably confirmed from the European Prospective Type 2 diabetes- detect pre-diabetes. Investigation into Cancer and Nutrition related gene Original Publication: In an interdisciplinary study led by Rui (EPIC)-Potsdam study. Rui Wang-Sattler et al.: Novel Wang-Sattler, scientists of the Research Unit As the concentration of the biomarkers in PPAR- AOX INS MAPK1 GR Activation Biomarkers for Pre-Diabetes Molecular Epidemiology, in collaboration with blood are indicative of pre-diabetes, this study Identified by Metabolomics. researchers from the Institutes of Structural suggests that preventive measures can be taken Inhibition Molecular Systems Biology Biology, Human Genetics, Experimental Genetics, The three metabolites are glycine, acetylcarnitine 8 (2012) 615 | doi: 10.1038/ msb.2012.43 Epidemiology II, the Genome Analysis Center C2 and lysophosphatidylcholine (LPC) 18:2. Physical interaction
Further authors from PPARG TCF7L2 HNF1A GCK IGF1 IRS1 IDE Transcription Helmholtz Zentrum München: Zhonghao Yu, Christina Holzapfel, Harald Grallert, Tao Xu, Signaling regulation Erik Bader, Kirstin Mittelstrass, Thomas Illig – Research Unit Same pathway Molecular Epidemiology Ana C. Messias – Institute of Structural Biology Katharina Heim, Holger Metabolomics studies have revealed that three metabolites are Three candidate biomarkers for pre-diabetes associated with seven type 2 diabetes-related genes. Prokisch, Thomas Meitinger – candidate biomarkers for pre-diabetes – an early form of type 2 Institute of Human Genetics diabetes. With the aid of these biomarkers, the disease can be Monica Campillos, Werner detected soon enough to halt or even prevent its development. Roemisch-Margl, Karsten Suhre – Institute of Bioinformatics and Systems Biology Barbara Thorand, Cornelia Huth, Christine Meisinger, Annette Peters – Institute of Metabolomics is the systematic study of the small-molecule Epidemiologiy II metabolite profiles of an organism. The analysis is performed Angela Döring, H.-Erich Wich- mann – Institute of Epidemi- by means of mass spectrometry or using an NMR spectrometry. ology I Christian Gieger – Institute of Genetic Epidemiology Cornelia Prehn, Martin Hrabě de Angelis, Jerzy Adamski – Institute of Experimental Genetics Heiko Lickert – Institute of Diabetes and Regeneration Research HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 62 63
BRIEF PROFILE BRIEF PROFILE DR. HARALD GRALLERT PROF. DR. DR. KARL-HEINZ LADWIG Research group leader, Role of Genetics in Type2 Relationship between Research Unit Molecular Leader of research group Epidemiology in the Institute Mental Health, Institute of of Epidemiology II, Helmholtz Epidemiology II, Helmholtz Zentrum München Diabetes Pathogenesis PTSD and Type 2 Zentrum München 2008–2010: Postdoc at the 2009: Hans Roemer Award of Institute of Epidemiology, the DGPM (German Association research unit Molecular Genome-wide association studies (GWAS) are Through meta-analyses with large numbers of Diabetes of Psychosomatic Medicine) Epidemiology and research and DKPM (German College of an effective method to detect genetic variations individuals (circa 133 000 and almost 150 000 group Epidemiology – Psychosomatic Medicine) Biosamples – Genomics that play a role in the pathogenesis of diabetes subjects) – also using a newly developed metab- since 2003: Professor of Psycho- 2007: PhD degree mellitus. These may help identify individuals at ochip – 53 gene regions with effects on glycemic People who suffer posttraumatic stress disorder 333 individuals showed signs of a pre-diabetic somatic and Psychological an early stage that have an increased risk of di- characteristics were identified or confirmed, and (PTSD) have a significant risk of developing type 2 metabolic state, a pre-form of diabetes. The Medicine at Technische abetes. Epidemiologists of Helmholtz Zentrum ten gene loci associated with type 2 diabetes diabetes. PTSD is an adjustment disorder after evaluation of the data revealed a significant Universität München since 2002: Scientist at the München therefore also participate in inter- were discovered. According to the scientists experiencing a trauma and leads to massive stress association of PTSD with type 2 diabetes; how- Institute of Epidemiology, national research consortia such as DIAGRAM involved in the studies, this high number of symptoms. An association between stress due to ever, a higher incidence of pre-diabetes related Helmholtz Zentrum München (DIAbetes Genetics Replication and Meta-anal- loci is an indication that the development of mental illness and diabetes has been discussed to psychological stress was not observed. 1990–2002: Head of GSF Clinical ysis Consortium) and MAGIC (Meta-Analyses of diabetes and its preliminary stages is so com- for a long time. Now for the first time, Karoline The scientists assume that the chronic stress Research Group, Klinikum Glucose and Insulin-related Traits Consortium), plex because it is based on many factors, each Lukaschek of the Institute of Epidemiology II at burden of PTSD patients leads to adjustments rechts der Isar, Technische Universität München which investigate the genetic causes of diabetes contributing only small effects. That is why it is Helmholtz Zentrum München and Johannes Kruse in the hormonal reaction patterns. This can since 1998: Head of the by means of GWAS, among other methods. In foreseeable that there will be no single effective of the Clinic for Psychosomatic Medicine and have a pathological impact on the metabolism Psycho-Physiological the consortia, the genetic association analyses therapy for all patients with diabetes. Rather, Psychotherapy of the University Hospital Giessen/ and the utilization of glucose. Elucidating the Laboratory at the German are centrally coordinated to identify and specify personalized, individually tailored approaches Marburg and colleagues have demonstrated a association between psychological factors and Heart Center Munich gene variants with reference to type 2 diabetes will be needed to gain control over this major, clear association between the two diseases. The metabolic disorders will therefore be an im- 1996: Habilitation 1984: PhD, Technische and related metabolic disorders. widespread disease. scientists analyzed the data of the population- portant task of diabetes research in the future. Unversität München based cohort study and administered a glucose According to the scientists, the treatment of tolerance test. In the cohort, a total of 50 people metabolic risk factors should already be part with PTSD were identified. 498 KORA participants of the therapy for patients with PTSD and other had manifest type 2 diabetes, and additionally mental illnesses. Original Publications: Andrew Morris et al.: Large- Scale Association Analysis Provides Insights into the Genetic Architecture and Pathophysiology of Type 2 Diabetes. Nature Genetics 44 (2012) 981 -988 | doi: 10.1038/ Original Publication: ng.2383 (DIAGRAM) Karoline Lukaschek et al.: Robert Scott et al.: Large-Scale Through meta-analyses with large numbers of individuals, 53 gene The presence of posttraumatic stress disorder is clearly associated Relationship Between Posttrau- Association Analyses Identify loci that impact blood glucose levels were discovered or earlier with the occurrence of type 2 diabetes. The cause is suspected to be matic Stress Disorder and Type New Loci Influencing Glycemic 2 Diabetes in a Population- findings were confirmed; 10 gene loci associated with type 2 diabetes an activation of the hormonal stress axis through permanent stress Traits and Provide Insight Based Cross-Sectional Study into the Underlying Biological were identified for the first time. symptoms. with 2970 Participants. Journal Pathways. Nature Genetics 44 of Psychosomatic Research 74 (2012) 991-1003 | doi: 10.1038/ (2013) 340-345 | doi: 10.1016/j. ng.2385 (MAGIC) jpsychores.2012.12.011 In genome-wide association studies (GWAS), state-of- Posttraumatic stress disorder (PTSD) is a mental illness which Further authors from the-art analysis techniques are used to detect genetic differences is preceded by stressful events that are exceptionally threatening or Further authors from Helmholtz Zentrum München: between healthy subjects and people with diseases such as diabetes catastrophic (trauma). The event must not necessarily relate to one’s Helmholtz Zentrum München: Julia Meyer, Martina Müller- mellitus. Thus, associations between genetic alterations and own person but can also be experienced with others – for example as Karoline Lukaschek, Jens Nurasyid, Christian Gieger – external characteristics can be detected, and genetic risk factors witness to an accident or an act of violence. Baumert, Rebecca Thwing Institute of Genetic Emeny, Maria Elena Lacruz, for the development and/or course of the disease can be identified. Epidemiology; Thomas Illig, Cornelia Huth, Barbara Norman Klopp – Research Unit Thorand, Christine Meisinger – Molecular Epidemiology; Institute of Epidemiology II Annette Peters, Barbara Rolf Holle – Institute of Health Thorand – Institute of Economics and Health Care Epidemiology II Management HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 64 65
BRIEF PROFILE DR. SANDRA HUMMEL Senior scientist Gestational Breastfeeding Reduces Diabetes/ Type 2 Diabetes – Pathogenesis and Prevention, Institute of Diabetes Research, Helmholtz Zentrum München Risk of Type 2 Diabetes 2011: Ernst Friedrich Pfeiffer Award of the German Diabetes Society Breastfeeding is healthy – this is true not time. Apparently even three years after birth, 2006: Research award of the only for the baby, but apparently also for the breastfeeding influences the concentration of German Society for Nutritional 80 Medicine mother. If she develops gestational diabetes two hormones that control hunger and satiety: 2003: Science Prize, Association during pregnancy, she can reduce her risk of the appetite-stimulating hormone ghrelin and No breastfeeding of Nutritional Scientists developing type 2 diabetes by about 40 percent the hormone PYY, which mediates a feeling of 2003: Research Fellowship, through breastfeeding. Gestational diabetes satiety. The novelty of this study presented here Breastfeeding Instituto San Raffaele, Milan, 60 Italy is a metabolic disorder limited to pregnancy is the finding that breastfeeding prevents type 2 ≤3 months Since 2002: Scientific staff that increases the risk of developing type 2 diabetes in the mother even over the long term. member, Institute of Diabetes diabetes after delivery. Impaired insulin release According to the findings of the Institute of Dia- Breastfeeding Research, Helmholtz Zentrum and reduced insulin sensitivity result in this betes Research, the duration of breastfeeding is >3 months München and Technische metabolic disorder characterized by elevated crucial: Only those who breastfed for more than 40 Universität München 2002: PhD degree blood glucose levels. Women who had to be three months had a 15-year risk of 42 percent treated with insulin during pregnancy bear the of developing type 2 diabetes compared to 72 greatest type 2 diabetes risk: Almost two thirds percent in mothers who breastfed less than 3 of this group of participants of a gestational months. The test subjects were able to reduce 20 diabetes study developed type 2 diabetes within their diabetes risk even more if they fed their three years after delivery; within 15 years baby during this period exclusively with breast even more than 90 percent developed type 2 milk (15-year risk of 34.8 percent). By breast- diabetes postpartum. Previous studies reported feeding, the participants were able to delay the a short-term positive effect of breastfeeding on development of type 2 diabetes by an average 0
the metabolism of the mother. These studies of ten years. Now the aim of the research group Incidence of type 2 diabetes after delivery in % indicate that breastfeeding for one to three led by Anette-Gabriele Ziegler is to investigate 0 3 6 9 12 15 months improves lipid and glucose metabo- the mechanisms that are responsible for this Years after delivery lism and reduces estrogen levels during that long-term effect of breastfeeding.
Cumulative incidence of a subsequent development of type 2 diabetes in women who had Women with gestational diabetes who breastfeed their baby have a gestational diabetes during pregnancy: Subjects who breastfed longer than three months 40 percent reduced risk of developing type 2 diabetes over the long had a significantly reduced risk of developing the disease. term. Especially mothers who breastfeed longer than three months Original Publication: Anette-Gabriele Ziegler et al.: benefit from this protective long-term effect. Long-Term Protective Effect of Lactation on the Development of Type 2 Diabetes in Women with Recent Gestational Diabetes Mellitus. Diabetes 61 (2012) 3167-3171 | doi: 10.2337/ Gestational diabetes (diabetes during pregnancy) increases the db12-0393 mother’s risk of developing type 2 diabetes later on. One woman in two develops type 2 diabetes within ten years after delivery, although initially her blood glucose levels returned to normal after pregnancy. Further authors from In Germany gestational diabetes occurs in about four percent of all Helmholtz Zentrum München: Anette-Gabriele Ziegler, Maike pregnancies. Wallner, Michaela Rossbauer, Minna H. Harsunen, Christiane Winkler – Institute of Diabetes Research HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 66 67
BRIEF PROFILE BRIEF PROFILE DR. JOACHIM HEINRICH PROF. DR. ANETTE-GABRIELE ZIEGLER Acting director, Institute of Air Pollution Promotes Type 1 Diabetes Epidemiology I, Helmholtz Director of the Institute of Zentrum München Diabetes Research at Helmholtz Zentrum München, Chair 1997–2011: Deputy director, Insulin Resistance Is Predicted by of Diabetes and Gestational Institute of Epidemiology Diabetes at Technische since 1992: Research group Universität München leader Environmental Epidemiology Airborne pollutants play an important role of insulin resistance increased by 17 percent. Autoantibodies 2009–2013: Member of the 1990–1992: Epidemiologist, board of the German Diabetes in the development of chronic diseases of the Also the distance of the residence to roads University of Wuppertal Association 1974–1989: Scientific assistant respiratory and cardiovascular systems; for with heavy traffic was significant: Near to busy 2007–2009: Director of Depart- and research group leader diabetes, however, no reliable data has been roads the insulin resistance increased by seven The autoimmune disease type 1 diabetes often largest of its kind in the world. Anette-Gabriele ment of Endocrinology and Biostatistics, Erfurt Medical available until now. Elisabeth Thiering and percent per 500 meters. These relationships manifests during childhood and adolescence. Ziegler and Christiane Winkler of the Institute Diabetes, Klinikum Schwabing, School Joachim Heinrich of the Institute of Epidemiol were independent of confounding factors such Characteristic markers of the disease are of Diabetes Research and their colleagues from Germany 1998: Ernst Friedrich Pfeiffer ogy I conducted a study on children to deter- as socioeconomic status, passive smoking, autoantibodies – i.e. immunoglobulins directed international cooperative projects found that Award of the German Diabetes mine a possible association of air pollution and or BMI. Air pollutants are potential oxidants against the body’s own components. They 70 percent of children who have more than Association insulin resistance, a precursor of type 2 diabetes. and can oxidize lipids and proteins directly appear when insulin producing cells in the one type of autoantibodies against islet cells 1996: Senior Clinician of the 3rd They evaluated blood samples and data from or activate oxidizing signaling pathways. This pancreas are destroyed and may be present in in the pancreas develop type 1 diabetes within Medical Department, Academic 397 10-year-old children of a prospective cohort oxidative stress may be an explanation for the young patient's blood already at the age of ten years. Over a period of 15 or 20 years, the Hospital Schwabing 1994: Dr. Bürger Büsing Award study. For all residential addresses of the chil- the development of insulin resistance due to six months to three years. In a 20-year period percentage of children is even 85 percent or of the German Diabetes Union dren since their birth, the respective traffic- traffic-related air pollutants. In the follow-up after the first appearance of so-called multiple almost 100 percent. Subjects with only one type 1993–1996: Heisenberg Fellow related air pollutant concentrations of particu observation of the cohorts, the researchers are autoantibodies – sooner or later depending of autoantibodies, however, develop type 1 of the German Research late matter and nitrogen dioxide (NO2) were now investigating whether their observations on the presence of certain risk factors – the diabetes only in 15 percent of the cases within Foundation at the Institute of modeled and related to insulin resistance at the also apply to older children and whether e.g. disease manifests. In order to determine the ten years, and children without autoantibodies Diabetes Research in Munich 1992: Habilitation age of ten years. The socio-economic status of a change of residence with altered particulate progression rate more precisely, scientists from almost never develop type 1 diabetes. 1991: Specialization (Board) in the families, the children’s exposure to passive pollution allows conclusions about the signifi- the Institute of Diabetes Research compared These results show that the development of Internal Medicine smoking and their birth weight, developmental cance of exposure in early childhood and then the data from their own studies (BABYDIET and type 1 diabetes is usually predictable. There- status and body mass index (BMI) were taken later on. Currently, the clinical relevance of an BABYDIAB) with the data of two other prospec- fore, the detection of autoantibodies provides BRIEF PROFILE into account. The statistical analyses revealed increased risk of insulin resistance caused by tive cohort studies (DAISY from Colorado and a relatively simple and cost-efficient way to DR. CHRISTIANE WINKLER that levels of insulin resistance were greater in particulate matter cannot be assessed. How DIPP from Finland). Overall, they were able diagnose type 1 diabetes at an early stage and, Research group leader of children with higher exposure to particulate air ever, the results support the hypothesis that the to analyze the results of 13 377 children over if applicable, in time to begin preventive and Type 1 Diabetes Cohorts at the pollution and nitrogen dioxide. Per 10.6 μg/m3 development of diabetes in adulthood is related a period of 20 years, making this study the therapeutic measures. Institute of Diabetes Research, additional NO2 content in the air, the incidence to environmental factors earlier in life. Helmholtz Zentrum München
since 2012: Ernst Friedrich Pfeiffer Award of the German Diabetes Association 2009: Fellowship at the Pediatric Epidemiology Center, University of South Florida, Tampa, USA Increased particulate air pollution increases children’s risk of devel- In type 1 diabetes, characteristic autoantibodies against islet cell since 2008: Post Doc Original Publication: oping a resistance to insulin. This insulin resistance is the precursor antigens often appear quite early in the blood of young patients. Forschergruppe Diabetes Elisabeth Thiering et al.: of type 2 diabetes. Through the detection of multiple autoantibodies, the disease can e.V. (from 2010 on Institute of Long-Term Exposure to Traffic- often be diagnosed in the preclinical stage. Diabetes Research, Helmholtz Related Air Pollution and Zentrum München) Insulin Resistance in Children. 2008: PhD degree Results from the GINIplus and LISAplus Birth Cohorts. Diabet- The insulin resistance syndrome – also known as the metabolic ologia 56 (2013) 1696-1704 | syndrome – refers to the common occurrence of several symptoms or Original Publication: doi: 10.1007/s00125-013-2925-x diseases: obesity, elevated fasting blood glucose and blood lipid levels Islet cell autoantibodies directed against different components Anette-Gabriele Ziegler et al.: and high blood pressure. This so-called deadly quartet increases the of the insulin-producing beta cells of the pancreas are characteristic Seroconversion to Multiple Islet Autoantibodies and Risk of risk of atherosclerosis, diabetes and heart disease. markers for type 1 diabetes. Due to the autoimmune process, the body Further authors from Progression to Diabetes in Helmholtz Zentrum München: is no longer sufficiently supplied with insulin; if the destruction of Children. Elisabeth Thiering, – Institute the beta cells exceeds a certain threshold, the disease manifests and Journal of the American of Epidemiology I blood glucose levels rise. Medical Association (JAMA) 309 Josef Cyrys, Christa Meisinger – (2013) 2473-2479 | doi: 10.1001/ Institute of Epidemiology II jama.2013.6285. HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 68 69
BRIEF PROFILE BRIEF PROFILE PD DR. PETER ACHENBACH DR. ANDREAS BEYERLEIN Deputy director of the Institute Progression of Infections Increase Leader of the research group of Diabetes Research, Epidemiology at the Institute of Helmholtz Zentrum München Diabetes Research, Helmholtz Zentrum München 2013: Habilitation Type 1 Diabetes Type 1 Diabetes Risk 2009: Ernst Friedrich Pfeiffer 2012: Postdoc, Technische Award of the German Diabetes Universität München Association 2011-2012: Consultant, Bavarian since 2008: Project leader Type 1 diabetes is an autoimmune disease. Just only in the factors spontaneous delivery or Islet autoimmunity refers to the presence of infections of the upper respiratory tract such as State Office of Statistics in the competence network since 2011: PhD degree, Ludwig- how quickly the autoimmune process progress- cesarean section. While half of the rapid pro- autoantibodies against insulin-producing beta nasopharyngitis (the common cold). Children Diabetes mellitus and head Maximilians-Universität of the Islet Autoantibody es and type 1 diabetes develops appears to gressors were delivered by cesarean section, cells of the pancreas. It is characteristic of with islet autoantibodies were infected at least München Standardization Program be dependent on an interplay of genetic and this was the case with only every sixth slow type 1 diabetes and most commonly appears twice in the first year, mainly with pathogens since 2007: Member of the environmental factors. Scientists of the Institute progressor. The greatest immunological differ- between the ages of six months to three years. of the respiratory tract. Children who had more research group Diabetes of TU of Diabetes Research have partly succeeded in ence was seen in the development of autoanti- Scientists at the Institute of Diabetes Research than five respiratory infections in the first year München elucidating relevant gene combinations. bodies against insulinoma-associated antigen-2 have investigated whether in this phase of life had the highest risk of islet autoimmunity. The 2005–2010: Early Career Patient- Oriented Diabetes Research The researchers led by Peter Achenbach and (IA-2A), which in general indicate a high infectious agents might be considered a poten- scientists suspect, however, that the increase Award of the Juvenile Diabetes Anette-Gabriele Ziegler analyzed data of the diabetes risk: The slow progressors showed a tial trigger for the dysregulation of the immune in autoimmune risk is not caused by a specific Research Foundation (JDRF/ BABYDIAB study. This prospective cohort study delayed development of IA-2A. Characteristic of system. They analyzed the data of children of virus but rather by the sum of infections and USA) includes participants from birth on who have the rapid progressors was a higher percentage the BABYDIET study who have relatives with the thus released inflammatory cytokines. 2001–2010: Scientific staff member at the Institute of at least one relative with type 1 diabetes. Two of risk variants of genes involved in immune type 1 diabetes and thus an increased risk for According to the principal investigator of the Diabetes Research Munich of extreme groups were compared with each regulation. These gene variants are individually islet autoimmunity. The parents kept a log of study, Anette-Gabriele Ziegler, and her col- the Research Group Diabetes other over an observation period of 20 years: connected to a relatively small increased risk of the infections occurring in the first three years leagues, frequent respiratory infections in the e.V. and physician at the the group of slow progressors – children who disease. However, if they occur in certain com- of life of the children – differentiated according first year of life represent a possible risk factor Municipal Hospital München- developed type 1 diabetes at the earliest ten binations, this seems to favor an early onset of to respiratory tract, gastrointestinal tract and for type 1 diabetes. In genetically disposed risk Schwabing (until 2007) 1998–2001: Postdoc at the years after the first appearance of autoantibodies the disease. This is especially true for genes other infections. Fever and medication were children, multiple episodes of colds in early Barbara Davis Center for – and the group of rapid progressors – children encoding for interleukin-2 (IL2), the alpha subunit also recorded and the blood of the children was childhood should be avoided if at all possible, Childhood Diabetes, University who developed the disease at the latest three of the IL-2 receptor (CD25), interleukin-10 and regularly analyzed for autoantibodies. and vaccinations or anti-inflammatory therapies of Colorado, USA years after their first appearance. interferon-induced IFIH1 helicase. In contrast, In the first year of life an association between should be taken into consideration as preventive Basically, as far as demographic factors were no difference could be found regarding the HLA respiratory infections and the presence of islet measures against type 1 diabetes. concerned, the children were comparable. With (human leucocyte antigen) gene variants that autoantibodies was observed – especially with respect to environmental factors they differed pose the greatest risk for type 1 diabetes.
The development of type 1 diabetes may take only a few months, Infections in the first months of life predispose to the later presence but also many years. A combination of specific risk gene variants, of autoantibodies, which are responsible for the development of type the early appearance of autoantibodies against the insulinoma- 1 diabetes. In particular, respiratory diseases in the first year of life, associated antigen-2 (IA-2A) and a birth by cesarean section seem especially an acute common cold (nasopharyngitis) appear to play Original Publication: to facilitate a rapid progression of the autoimmune disease. an important role. Andreas Beyerlein et al.: Original Publication: Respiratory Infections in Early Peter Achenbach et al.: Life and the Development of Characteristics of Rapid vs Slow Islet Autoimmunity in Children Progression to Type 1 Diabetes at Increased Type 1 Diabetes in Multiple Islet Autoantibody- Type 1 diabetes is the most common metabolic disease in In islet autoimmunity the immune system is mistakenly directed Risk. JAMA Pediatrics 167 Positive Children. Diabetologia childhood and adolescence. The body’s immune system attacks the against endogenous components, namely against various proteins (2013) 800-807 | doi: 10.1001/ 56 (2013) 1615-1622 | doi: insulin-producing cells in the pancreas and destroys them. This of the insulin-producing beta cells of the pancreas. These cells are jamapediatrics.2013.158 10.1007/s00125-013-2896-y autoimmunity, which underlies the metabolic disorder, is based on gradually destroyed and insulin production is stopped – the outcome a genetic predisposition and is influenced by environmental factors. is the development of type 1 diabetes. Further authors from Further authors from Type 1 diabetes can occur at any age. The peak incidence is during Helmholtz Zentrum München: Helmholtz Zentrum München: puberty from age 10 to 15 years. Fabienne Wehweck, Maren Daniela Höfelmann, Anette- Pflueger, Anette-Gabriele Gabriele Ziegler – Institute Ziegler – Institute of Diabetes of Diabetes Research Research HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 70 71
BRIEF PROFILE BRIEF PROFILE DR. STEFANIE EYERICH DR. JOACHIM HEINRICH Leader of the junior research Interplay of More Risk Genes Acting director of the Institute group T Cell Biology in Health of Epidemiology I of Helmholtz and Disease at the Center of Zentrum München Allergy and Environment (ZAUM)/ Institute of Allergy Cytokines in Asthma for Allergies 1997–2011: Deputy Research, Technische director of the Institute of Universität and Helmholtz Epidemiology of Helmholtz Zentrum München Zentrum München The cytokine interleukin-22 may control the and IFN- are apparently antagonists. In the In a meta-analysis of several genome studies an Heinrich of the Institute of Epidemiology I. This since 1992: Leader of the 2013: Robert Koch Postdoctoral research group Environmental extent of asthmatic lung inflammation, according presence of IFN- , IL-22 cannot fully develop its international team of scientists has identified ten comprehensive genetic analysis in relation to the Award for Immunology, Epidemiology ACTERIA Early Career Research to a study by an international research team. The positive characteristics, and this leads to dimin- genes that are involved in the development of objective measurement of allergic sensitization 1990–1992: Epidemiologist, Prize for Allergology analysis of T-helper cells derived from the lungs ished wound healing responses. On the other allergic sensitization. In the genome-wide asso- enables an assessment of the identified genes University of Wuppertal 2012: Dr. Ernst Wiethoff Award of patients with asthma detected the presence of hand, however, IL-22 also suppresses the pro-in- ciation studies (GWAS), the scientists correlated as risk factors for allergic diseases. In addition, 1974–1989: Scientific assistant 2011: Egon Macher Award of the T-helper cell type Th22, which was originally flammatory effect of IFN- in the inflammatory the genetic profile of the study participants with all of these genes showed a correlation with and leader of the research the Association of Dermatology group Biostatistics Erfurt Research described in the skin. Interestingly, however, the process. The results suggest that the therapeutic the presence of specific IgE antibodies. They the occurrence of allergic manifestations such Medical School 2010-2012: Assistant to the lead cytokine of the Th22 cells, interleukin (IL)-22, administration of interleukin-22 or measures that discovered that ten loci are involved in a total as hay fever and asthma. The results of this group leader, Center of Allergy was co-produced in a number of T cells with support its production could reduce the acute of 25 percent of all allergic sensitizations, the meta-analysis indicate that enormous genetic and Environment gamma interferon (IFN- ). IFN- is considered inflammatory response in asthma. However, this immunological process in which antibodies form diversity underlies allergic diseases. Further 2009-2010: Postdoc, Center of to be pro-inflammatory because, among other protein is ambivalent in its effect. Too much IL-22 against allergens, which are actually harmless more, lifestyle factors and environmental Allergy and Environment 2008-2009: Postdoc, National things, it stimulates the production of adhesion can lead to excessive proliferation of epithelial substances in the environment. These antigens stresses play an important role in future allergy Heart and Lung Institute (NHLI), molecules in epithelial cells, while interleukin-22 cells, a phenomenon that is e.g. observed in pso- subsequently cause the allergic symptoms. research and the treatment of patients. Now, Department of Allergy and has the opposite effect – it promotes defense riasis. In addition, IL-22 interacts strongly with The researchers analyzed data from more than based on the genetic information, the scientists Clinical Immunology, Imperial mechanisms and wound healing. In an in vitro other interleukins, and these interactions are 10 000 people with allergic sensitization and want to investigate the involved molecular College London, UK model using human bronchial epithelial cells, not yet sufficiently understood. As next step the approximately 20 000 control subjects. Among mechanisms in more detail in order to obtain 2008: PhD degree the researchers examined the interaction of the scientists therefore want to study the interaction them were participants of the German birth new insights into the pathomechanisms of aller- two substances and demonstrated that IL-22 of IL-22 and IFN- in the mouse model. cohorts GINIplus and LISAplus; their evaluation gies and other immune diseases. was carried out by Marie Standl and Joachim
Scientists at the Center of Allergy and Environment (ZAUM) of In a meta-analysis of several genome studies, an international research Helmholtz Zentrum München and Technische Universität München team which included scientists of the Institute of Epidemiology I has Original Publication: Klaus Bønnelykke et al.: Original Publication: investigated the anti-inflammatory role of interferon-22 in allergic identified 10 genes that together are responsible for the development of Davide Pennino et al.: IL-22 Meta-Analysis of Genome-Wide asthma in the framework of an international research group. allergic sensitization. Suppresses IFN-ɣ–Mediated Association Studies Identifies Lung Inflammation in Ten Loci Influencing Allergic Asthmatic Patients. Sensitization. Nature Clin Immunol. 131 (2013) 562-70 Genetics 45 (2013) 902-906 | | doi: 10.1016/j.jaci.2012.09.036. doi: 10.1038/ng.2694 Epub 2012 Nov 19. Both interleukins (IL-x) and interferons belong to the family Allergic diseases are increasing throughout the world. In Europe of cytokines. They are endogenous tissue hormones, which act as alone an estimated 80 million people are affected. The reason for the Further authors from Further Authors from communication factors between immune and tissue cells. allergic reaction is a complex gene-environment interaction. Helmholtz Zentrum München: Helmholtz Zentrum München: Marie Standl, Carla Tiesler, Carsten B. Schmidt-Weber – Elisabeth Thiering, Institute of Allergy Research Institute of Epidemiology I Davide Pennino, Renate Effner, Katharina Schramm, Institute of Maria Quaranta, Viviana Human Genetics Marzaioli, Liliana Cifuentes – Melanie Waldenberger, Center for Allergy and Research Unit Molecular Environment Epidemiology HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 72 73
BRIEF PROFILE PROF. DR. ROLF HOLLE Leader of the research group Cost of Medical Care in 5 Economic Evaluation, No COPD Institute of Health Economics and Healthcare Management, Stage I Helmholtz Zentrum München Early Stages of COPD 4 Since 2005: Adjunct professor Stage II at the Medical Faculty of Health care utilization Ludwig-Maximilians- Scientists of the Institute of Health Economics and without COPD taking age, sex and level of Universität München 3 and Health Care Management at Helmholtz education into account. The results show that 1995: Habilitation, University of Heidelberg Zentrum München have investigated the associ people with early stage (I) COPD do not cause 1990: Dr. biol. hom., Medical ation between early stages of COPD and the substantially higher costs for medical treatment Adjusted Faculty, University of Giessen utilization of medical care. The researchers based than participants without the disease. 2 total costs per year 1980-1995: Scientific staff their investigation on the KORA study comprising However, as soon as the moderate stage is in euros member at the University of Giessen and the University of more than 2000 participants between 40 and reached, costs increase and are on average Heidelberg 90 years of age. The aim of the study was to 990 euros higher per year for people with COPD No COPD 1822 determine whether already in the early stages compared to people with normal lung function. 1 Stage I 1830 (+0 %) of COPD there are excess costs for medical care. In view of the high incidence of COPD, this means Stage II 2812 (+54 %) COPD is commonly known as smoker’s cough; that alone for the treatment of this stage, annual the official name is chronic obstructive pulmo- costs of about two billion euros are incurred nary disease. The disease is incurable; it is only for the German health care system. The total 0 possible to slow its progression. An estimated costs of COPD are many times higher, especially Number of outpatient visits Days in hospital Number of medications 13 percent of adults in Germany over 40 years when patients in stages III and IV are included (3-month period) (12-month period) (7 days) of age suffer from this disease, whereby in the in the cost calculation. In order to quantify these early stages it usually remains undiagnosed. costs as well, the research group collaborates The researchers calculated the costs per within the Competence Network COPD, where year incurred by visits to the doctor, hospital information from 2700 patients across Germany is stays and medications for these individuals. being collected and analyzed. So far, from these Comparison of the frequency of outpatient visits, hospital stays and use of medication between By means of a pulmonary function test they results, the researchers conclude that suitable healthy individuals and subjects with COPD in the mild stage (I) or moderate stage (II). The resulting identified test subjects with reduced lung preventive measures are needed for COPD not costs were estimated, taking into account age, sex and level of education. function and classified them into mild (Stage I) only from a medical perspective but also from an or moderate (Stage II) COPD. In computer- economic perspective to keep the disease from assisted interviews using detailed question progressing to a more advanced stage. First and naires, participants were asked about their visits foremost, this means that smokers who already
to the doctor, hospital stays and medications. suffer from mild COPD should be motivated to Original Publication: From this data, their costs for medical care stop smoking, since smoking cessation is one People who suffer from a moderate form of COPD cause around 990 Petra Menn et al.: Direct were derived. Then the researchers compared of the most effective interventions to slow the euros higher medical costs due to illness per year than comparable Medical Costs of COPD – An the calculated costs between participants with worsening of the disease. individuals who do not have the disease. For the treatment of this Excess Cost Approach Based on disease stage alone, this means annual costs of about two billion euros Two Population-Based Studies. Respiratory Medicine 106 for the German healthcare system. Therefore preventive measures (2012) 540-548 | doi: 10.1016/j. are needed to stop the development and progression of COPD. rmed.2011.10.013
Further authors from Helmholtz Zentrum München: Petra Menn, Jürgen John – COPD stands for chronic obstructive pulmonary disease; Institute of Health Economics It is caused by a chronic inflammatory pulmonary disorder that leads and Healthcare Management to the narrowing of the small airways. It occurs primarily in smokers Joachim Heinrich, Stefan and is often accompanied by coughing, excessive mucus production Karrasch, Holger Schulz – Institute of Epidemiology I and and breathlessness. Comprehensive Pneumology Center Munich (CPC) Annette Peters – Institute of Epidemiology II HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 74 75
BRIEF PROFILE DR. JOVICA NINKOVIC Scientist at the Institute of Key to Neurogenesis Stem Cell Research, Helmholtz Zentrum München
2010: Scopus Neuroscience Award The formation of nerve cells is mainly restrict- a major role both in the development of the 2005–2007: Postdoc, Institute of ed in mammals to the development phase and brain and in adult neurogenesis, the scientists Stem Cell Research takes place in the adult stage only in a few showed that Pax6 interacts with the so-called BAF regions of the forebrain. The usual case in BAF complex, which can alter the chromatin Pax6 the adult brain is the formation of supporting structure, and that this interaction determines cells, also called glial cells. In fact, even stem the fate of the neural progenitor cells. Through cells that were transplanted as a therapy for the interaction, the chromatin is modified in Transcription neurodegenerative diseases usually develop such a way that certain genes that serve the factors into glial cells instead of the desired neurons. regulation of neuronal differentiation become The few regions of adult neurogenesis offer an accessible. As a result, the genes necessary Pou3f4 Nfib Transcription-relevant opportunity to investigate just how neurons for neuronal differentiation are more strongly BAF complex can be formed even in the adult brain. Both expressed and the fates of neuronal cells – even in the developing brain and in the adult brain in surroundings where otherwise only glial cells numerous transcription factors are involved in are formed – are stabilized. A loss of function of neurogenesis. However, it is still unclear how Pax6 or BAF – depending on the surroundings – the final differentiation of the progenitor cells is leads to the formation of glial cells instead of controlled at the molecular level. neurons. Thus, the scientists describe for the first Sox11 One key mechanism in this process was eluci- time certain molecular prerequisites of neurogen- dated by the team led by Jovica Ninkovic and esis in the adult brain. This could be the basis for Magdalena Götz of the Institute of Stem Cell Re- new therapies, e.g. to stimulate the formation of search. By searching for the interaction partners nerve cells in neurodegenerative diseases or after Diagram showing the interaction of transcription factors that decide of the transcription factor Pax6, which plays brain injuries and to replace damaged cells. the fate of neuronal progenitor cells.
Original Publication: Neural progenitor cells can differentiate into different cell types Jovica Ninkovic et al.: The BAF in the adult brain: into new neurons, but also into glial cells. In Complex Interacts with Pax6 the study, it was shown that the transcription factor Pax6 causes a in Adult Neural Progenitors to Establish a Neurogenic change in chromatin structure by interacting with the so-called BAF Cross-Regulatory Transcriptional complex and thereby influences the fate of neural progenitor cells. Network. Cell Stem Cell 13 (2013) 403-418 | doi: 10.1016/j. stem.2013.07.002
Further authors from A nerve cell or neuron is a cell that is specialized in signal Helmholtz Zentrum München: transduction and synaptic transmission. Neurons are found in Andrea Steiner-Mezzadri, almost all multicellular animals. All of the nerve cells of an Giacomo Masserdotti, Stefania organism and the glial cells comprise the nervous system. Petricca, Judith Fischer, Magdalena Götz – Institute of Stem Cell Research Johannes Beckers, Martin Irmler, Chichung D. Lie – Institute of Experimental Genetics
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BRIEF PROFILE BRIEF PROFILE DR. LEDA DIMOU PROF. DR. WOLFGANG WURST Scientific staff member of the Oligodendrocytes and Faster Production Director of the Institute of Institute of Stem Cell Research, Developmental Genetics, Helmholtz Zentrum München Helmholtz Zentrum München, and Institute of Physiological chair of Developmental Genetics, Genomics at Ludwig- Multiple Sclerosis of Disease Models Technische Universität München Maximilians-Universität München 1994–1997: Junior group leader 1989–1994: Scientific staff since 2011: Leader of a Oligodendrocytes are cells of the central nerv- where the neuronal cell bodies are found. The An efficient method for the rapid production that are discovered using high-throughput member, Samel Lunenfeld research group at the Institute Research Institute of the Mount ous system that produce the myelin sheath, a aim of the researchers of the Institute of Stem of mouse disease models has been developed analyses of the human genome. of Physiological Genomics at Sinai Hospital, Toronto, Canada Ludwig-Maximilians- lipidous biomembrane which coats the axons Cell Research was to investigate whether at Helmholtz Zentrum München. Mouse models Scientists of the Institute of Developmental 1988–1989: Postdoc, University Universität München of nerve cells to provide insulation that allows this difference is cell-intrinsic or whether it is are used for the genetic analysis of disease Genetics have succeeded in developing a faster of Göttingen and guest scientist at electrical signals to propagate more efficiently. dependent on the local environment. In the mechanisms and are still considered to be way to produce mouse disease models. By Helmholtz Zentrum München This insulation is necessary in order to ensure mouse model, through transplantation of the indispensable for this purpose. In most cases, microinjection of so-called TALENs (Transcription BRIEF PROFILE 2003–2006: Postdoc in the PROF. DR. MARTIN a rapid nerve conduction velocity. progenitor cells, the researchers observed models are used which are produced Activator-like Effector Nucleases) and synthetic Institute of Brain Research of HRABE DE ANGELIS the University of Zurich In some neurological diseases and in particular how these develop independently from their by targeted mutations in embryonic stem cells oligodesoxynucleotides directly into the embryos 1998–2002: PhD at the in multiple sclerosis, the immune system original surroundings. The result was that (ES cells). However, this production process in the one-cell stage, any desired mutation or Director and chair of the University of Heidelberg and at destroys the myelin. As recent studies have the differences are primarily cell-intrinsic: is complex and time-consuming, since among deletion can be induced within two days and can Institutes of Experimental the Max Planck Institute shown, depending on their location in the brain, Progenitor cells from the white matter develop other steps, targeting vectors must be con- also be reversed. Since for this purpose neither Genetics, Helmholtz Zentrum of Experimental Medicine, München and Technische Göttingen oligodendrocytes can regenerate throughout life in both brain regions into myelin-producing structed with selection markers, mutated ES ES cultures nor targeting vectors are required, Universität München, member until 1998: Study of Biology from oligodendrocyte progenitor cells. The team oligodendrocytes. Progenitor cells from the cells must be isolated and germline chimeras this technology enables immediate changes in of the board of the German at the University of Heidelberg led by Leda Dimou has now taken a closer look gray matter are less effective. The next step for must be produced. All of these procedures are the germ cells, so that heterozygous mutants are Center for Diabetes Research at these oligodendrocyte progenitor cells to the researchers will be to identify the factors very laborious and time intensive. Including available within 18 weeks. This novel method is identify the reason for these differences in their which determine the effectiveness of these all steps, the scientists often need one to two thus significantly faster than the previously used 1997–2000: Leader of the research group Functional differentiation potential. oligodendrocyte progenitor cells. Their goal is years to produce a knockout mouse model methods. Through the intelligent production of Genetics Depending on the brain region in which the to define conditions in which these progenitors using these methods. This poses a hurdle for mouse models required for drug development, 1994–1997: Postdoc, The Jackson progenitor cells are located, a smaller or greater will always differentiate into oligodendrocytes the analysis of the ever-increasing number of the number of experimental animals needed for Laboratory, Maine, USA quantity of oligodendrocytes is generated that form myelin. Even though a therapy for known human disease-associated mutations this purpose can be drastically reduced. which can produce myelin. Progenitor cells in multiple sclerosis still appears to be far in the BRIEF PROFILE DR. RALF KÜHN the white matter of the brain, which consists distance, this research is an important contri- primarily of nerve fibers, generate more bution to understanding the origin and course Scientific team leader, Institute oligodendrocytes than those in the gray matter, of such neurological diseases. of Developmental Genetics, Helmholtz Zentrum München
1998–2002: Head of Mouse By microinjection of TALENs and synthetic oligodesoxynucleotides, Genetics, Artemis Pharmaceu- Oligodendrocytes are cells of the central nervous system that the scientists altered the genes in the fertilized egg cells of mice so ticals enable nerve cells to efficiently conduct electrical signals. Scientists that all progeny cells were equipped with the same mutation. Because 1994–1998: Postdoc and of the Institute of Stem Cell Research have now gained new insights through this method the laborious steps to produce targeted mutants scientific assistant, University of Cologne into the origin and development of oligodendrocytes, which may are not required, animal models can be established much faster and play an important role in multiple sclerosis. using substantially fewer experimental animals. Original Publication: Benedikt Wefers et al.: Original Publication: Direct Production of Mouse Francesca Viganò et al.: Trans- Disease Models by Embryo plantation Reveals Regional Microinjection of TALENs and Differences in Oligodendrocyte Multiple Sclerosis (MS) is a chronic inflammatory disease of the TALENs – Transcription Activator-like Effector Nucleases Oligodeoxynucleotides. Proc. Differentiation in the Adult central nervous system and is caused by demyelination of the nerves are modular enzymes that recognize and cleave specific double- Natl. Acad. Sci. U.S.A. 110 Brain. Nature Neuroscience in which the body’s own immune cells attack the myelin sheaths stranded DNA sequences. It is possible to create different sequence- (2013) 3782-3787 | doi: 10.1073/ (2013) | doi: 10.1038/nn.3503 of the nerve axons. The cause of this autoimmune reaction is not specific variants with which virtually all genes in the genome can pnas.1218721110 yet fully understood. MS is one of the most common neurological be cleaved and altered by co-administration of synthetic oligodeoxy Further authors from Further authors from diseases in young adults. To date, no cure has been found. nucleotides. Thus, specific genes can be removed selectively, and Helmholtz Zentrum München: Helmholtz Zentrum München: genetic defects can be incorporated into the cell or repaired. Benedikt Wefers, Melanie Francesca Viganò, Magdalena Meyer, Oskar Ortiz, Jens Götz – Institute of Stem Cell Hansen – Institute of Research Developmental Genetics HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 78 79
BRIEF PROFILE PROF. DR. MAGDALENA GÖTZ Human Glial Cells Can Trnp1 Regulates Director, Institute of Stem Cell Research, Helmholtz Zentrum München and chair of Physiological Genomics at Be Reprogrammed Expansion of Ludwig-Maximilians- Universität München
2014: Ernst Schering Award The regeneration of functional neurons is the surgery of adult epilepsy patients, Marisa Cerebral Cortex 2013: ERC Advanced Investigator Grant and Remedios Caro an innovative approach to the therapy of Karow and her colleagues showed that specific Almela Prize neurodegenerative diseases such as Alzheimer’s cells of the cerebral cortex (cells derived from 2010: Federal Cross of Merit disease or stroke. In the adult mammalian brain, pericytes) can be reprogrammed into neurons with ribbon however, most areas no longer contain neuronal through the retrovirus-mediated expression of Different brain regions have different tasks and that normally exhibit smooth, unfolded brains. 2008: Alzheimer Research Award stem cells or progenitor cells from which new the two transcription factors Sox2 and Mash1. must be specifically expanded as required. In Trnp1 is thus a key protein for the expansion of the Hans and Ilse Breuer Foundation neurons could be formed. Several years ago, These induced neurons fire action potentials and the forebrain of mammals, the cerebral cortex – and folding of the cerebral cortex. During fetal 2007: Hansen Family Award members of the Institute of Stem Cell Research form networks with other neurons; thus, they which is responsible for cognitive function – development it is dynamically controlled: In the and Gottfried Wilhelm headed by Magdalena Götz showed in a mouse are able to integrate themselves into neuronal is usually highly folded and expanded. The early phases of development Trnp1 levels are Leibniz Prize of the German model that by selective transfer of individual networks. This shows for the first time that there more folds and wrinkles there are, the larger high. This favors the formation of radial glial Research Foundation transcription factors it is possible to reprogram are cells in the adult brain which can be directly the surface and the better the brain can absorb cells, and specific brain regions expand. Later, 2000: Habilitation 1997–2003: Scientist glial cells – i.e. supporting cells with multiple reprogrammed into functional neurons for and process information. In humans, the brain Trnp1 levels drop again to lower levels. As a and research group leader at functions – to nerve cells. Transcription factors therapy purposes – without having to take a surface of the fetus is mostly smooth until consequence, the formation of various progeni- Max Planck Institutes in are regulatory proteins that control which genes detour via pluripotent cells. On the basis of approximately the sixth month of pregnancy; tor cells and glial cells is stimulated, and a par- Göttingen and Munich are active or inactive in the cells. Now a research this knowledge, researchers are seeking active it is not until after this that the folding begins. ticularly large number of newly formed neurons 1992–1996: Postdoc in Tübingen, team led by Magdalena Götz and Benedikt agents to activate the reprogramming of glial Until this study, it was completely unknown arrange themselves in a folded structure. London and Harlow Berninger has succeeded in proving that the cells in patients with neurodegenerative diseases which mechanisms trigger the expansion and This molecular mechanism is particularly animal experimental approach is also applicable to or brain traumas and thus to initiate a self-healing folding of the brain in the course of fetal devel- interesting because both the expansion and the human glial cells. Using specimens derived from process in the injured areas of the brain. opment. Now for the first time, Magdalena Götz folding of the brain are regulated by the same and her team have identified the corresponding molecule – Trnp1. Thus, Trnp1 represents a very molecular mechanism in the mouse model: promising approach for investigation of the The responsible protein is the nuclear protein cellular and molecular mechanisms underlying Trnp1, whose dynamic regulation triggers an these complex processes – an approach that enormous proliferation of neurons of the cere- Götz and her team want to pursue further. bral cortex and stimulates folding even in mice
For the first time the formation of new nerve cells from somatic During the fetal development of many mammals the cerebral cortex cells of the human brain has succeeded: Specific cells of the adult increases in size and becomes folded. Scientists of Helmholtz human cerebral cortex could be reprogrammed into functioning Zentrum München have now succeeded in identifying the key protein Original Publication: Original Publication: Marisa Karow et al.: Repro- neurons with the aid of two transcription factors. responsible for this process. Ronny Stahl et al.: Trnp1 Regu- gramming of Pericyte-Derived lates Expansion and Folding of Cells of the Adult Human Brain the Mammalian Cerebral Cortex into Induced Neuronal Cells. by Control of Radial Glial Fate. Cell Stem Cell 11 (2012) Cell 153 (2013) 535-549 | doi: 471-476 | doi: 10.1016/j. 10.1016/j.cell.2013.03.027 stem.2012.07.007 The brain consists of two main types of cells: the neurons, which The cerebral cortex is the neuron-rich outer layer of the transmit information, and the glial cells, which have a supporting cerebrum. Depending on the region, it is only two to fivemillimeters function and are involved in the metabolism of the brain. In many thick and is part of the gray matter of the cerebrum. The nerve Further authors from Further authors from degenerative diseases of the brain – stroke, Alzheimer’s disease, fibers of the neurons of the cerebral cortex extend below the cortex Helmholtz Zentrum München: Helmholtz Zentrum München: Ronny Stahl, Tessa Walcher, Parkinson’s disease – the neurons are primarily damaged. and form the white matter of the cerebrum that consists largely of Giacomo Masserdotti, Sergio Gregor Alexander Pilz, Silvia Gascón – Institute of Stem Cell myelinated nerve fibers bundled into tracts. Cappello – Research Institute of Stem Cell Research Muhammad A. Khan, Martin Irmler, Johannes D. Chichung Lie – Institute of Beckers – Institute of Experi- Developmental Genetics mental Genetics HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 80 81
BRIEF PROFILE PROF. DR. VIGO HEISSMEYER Head of the research unit How Roquin Family Molecular Immune Regulation in the Institute of Molecular Immunology, Helmholtz Zentrum München Proteins Control T Cells since 2012: Chair of Systemic Immunology in the Institute of Immunology at Roquin proteins control the activation and If these T cells then trigger an immune response Roquin-1san Roquin-2 Ludwig-Maximilians- differentiation of T cells by regulating their gene against the body’s own structures, a clinical Universität München 2011: ERC Starting Grant expression at the level of messenger RNA. The picture emerges that is very similar to lupus 2009-2011: Research group function of the RNA-binding proteins is first and erythematodes, an autoimmune disease that leader at the Institute of foremost to ensure immunological tolerance and attacks the skin and internal organs. A single 1 Molecular Immunology to prevent excessive immune reactions – such as point mutation in the Roquin-1 gene, i.e. the
2001–2005: Postdoc at Proteins Harvard Medical School, in autoimmune diseases. exchange of a single amino acid in the protein, Center for Blood Research Katharina Vogel and Stephanie Edelmann of leads to such a disease. Interestingly, in this 2000–2001: Postdoc at the the Institute of Molecular Immunology showed case the Roquin-2-protein is unable to take over Max Delbrück Center for how the two proteins, Roquin-1 and Roquin-2 the function of the defective Roquin-1, resulting Molecular Medicine can replace each other functionally and which in a complete loss of the Roquin function. The consequences result from the combined loss of research team also identified the molecular both Roquin genes. In the case that the Roquin- targets of the Roquin proteins, the Icos and Induce 1san form is present in a single point mutation, Ox40 costimulator mRNAs. degradation Roquin-1 inhibits the function of Roquin-2. In the This research demonstrates that the Roquin-1 absence of Roquin-1, Roquin-2 takes over and and 2 proteins are of great importance for 2 compensates for its function. The proteins are T cell differentiation in immune reactions. consequently interchangeable in their molecular In future studies, the focus will be on eluci-
function and fulfill a kind of reserve function for dating the regulation of these factors because Regulation of mRNA expression each other. The loss of both Roquin genes leads this regulation mechanism can be used as a to an uncontrolled accumulation of effector T therapeutic target in the treatment of auto Icos 0x40 Original Publication: cells and particularly of follicular helper T cells. immune diseases. Katharina Vogel et al.: Roquin Paralogs 1 and 2 Redundantly Repress the Icos and Ox 40 Costimulator mRNAs and Control Follicular Helper T Roquin-1/-2 Cell Differentiation. Immunity 38 (2013) 1-14 | doi: 10.1016/j. The two genetic variants Roquin-1 and Roquin-2 are important 3 immuni.2012.12.004 components in the activation and differentiation of T cells. The proteins encoded by them are interchangeable in their molecular function, and defects in the Roquin-1 gene can cause autoimmune Lymphocytes CD4 T cell Tfh cell differentiation Further authors from Helmholtz Zentrum München: diseases. For the first time, scientists have now analyzed the Katharina Vogel, Stefanie Edel- complex interaction of the two proteins and have examined their mann, Katharina M. Jeltsch, activity as regulators of gene expression. Gitta A. Heinz, Sebastian C. The proteins Roquin-1 and Roquin-2 repress the Icos and Ox40 costimulator mRNAs and regulate Warth, Kai P. Hoefig, Claudia the differentiation of T cells. Lohs, Elisabeth Kremmer – Institute of Molecular Immu- nology Autoimmunity is defined as the inability of an organism to Jessica Zöller, Mathias Heiken- recognize its structural components as endogenous. This leads to wälder – Institute of Virology a pathological reaction of the immune system against endogenous Frauke Neff – Institute of molecules or tissues which is manifested as an autoimmune disease. Pathology Joel Schick, Wolfgang Wurst – The exact causes for the dysregulation are not yet known. Institute of Developmental Genetics Arie Geerlof – Institute of Structural Biology HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 82 83
BRIEF PROFILE BRIEF PROFILE DR. PHILIPP A. GREIF PROF. DR. WOLFGANG HIDDEMANN Scientific staff member Personalized Leukemia of the Clinical Cooperation Director of the Department of Group “Pathogenesis of Acute Internal Medicine III, Myeloid Leukemia” at University Hospital of Munich, Helmholtz Zentrum München Therapy Appears chair of Internal Medicine with a focus on hematology since 2012: Junior research and oncology at Ludwig- group leader, German Cancer Maximilians-Universität Consortium (DKTK), partner within Reach München, head of the Clinical site Munich Cooperation Group “Pathogene- 2010: Merit Award International sis of Acute Myeloid Leukemia” Society of Oncology and Biomarkers, Research Award Cancer is caused by mutations in the genome FLT3 receptor mutations in this leukemia group Normal cells Acute myeloid Acute myeloid 1992–1998: Director of the from the Anne Liese Gaebel due to different factors. The gene mutations provide a new target for personalized treatment leukemia leukemia + inhibitor Department of Hematology Foundation mostly affect the regulators of cellular metab- of the disease. Inhibitors of the FLT3 receptor and Oncology, University of since 2008: Resident physician, Göttingen olism or cell growth. As a consequence, the are already available and can now be adminis- Department of Internal Medicine 1986: Senior physician at the III, University Hospital of Munich cells undergo malignant transformation and tered to the affected patients. University Hospital Münster 2005-2008: Postdoc, Clinical Co- proliferate in an uncontrolled manner. Many The study was conducted by the clinical coop- 1978–1979: Research fellow operation Group “Pathogenesis of such gene mutations have been identified in eration group “Pathogenesis of Acute Myeloid N676K N676K at the Memorial Sloan Ketter- of Acute Myeloid Leukemia” at leukemia. Leukemia”, a joint institution of Helmholtz MAPK MAPK MAPK ing Cancer Center, New York Helmholtz Zentrum München 1976–1992: Clinical training 2004–2005: Human Genetics In about one third of patients with acute mye- Zentrum München and the Department of in the Department of Medicine Programme, World Health loid leukemia (AML) the malignant cells have Internal Medicine III at the University Hospital A, University of Münster Organization (WHO), Geneva a mutation in the growth-regulating receptor of Munich. The aim of the clinical cooperation 1975–1976: Medical assistant in FLT3. As the team of scientists headed by Dr. group (CCG) is to identify leukemia-causing the Institute of Pathology at the Philipp Greif and Professor Karsten Spieker- mutations and to investigate why certain mutations University of Münster, the Department of Medicine at the mann have now discovered by means of exome can cause leukemia. The head of the CCG Wolfgang University Hospital of Münster sequencing, blood cancer cells from a sub- Hiddemann emphasizes the importance of this and the Surgical Department at stantial number of patients in a subgroup of interdisciplinary collaboration: The results show the Mathias Spital Rheine AML (so-called core-binding factor leukemias) in an exemplary way how innovative research also carry mutations in this receptor. The gene methods, such as high-throughput DNA alterations at position N676 were previously sequencing, allow discoveries, even in structures unknown and now allow a new classification of that have already been thoroughly examined. this leukemia form, which is characterized by These insights into the molecular basis of a particularly high cell count. In addition, the disease open up new treatment options according to the researchers, the newly identified for patients.
Specific mutations of the FLT3 receptor may contribute to the Normal cell Original Publication: Sabrina Opatz et al.: Exome development of acute myeloid leukemia. The Flt3 receptor regulates The mutation N676K is a new target for the treatment of acute myeloid leukemia. Patients with Sequencing Identifies Recurring cell growth; activating gene mutations promote uncontrolled prolif- this mutation can be identified by this marker, and the uncontrolled cell growth can be inhibited FLT3 N676K Mutations eration of white blood cells. This finding of the clinical cooperation by inhibitors of the growth-regulating FLT3 receptor. Cancer cell in Core-Binding Factor group “Pathogenesis of Acute Myeloid Leukemia” can be used to Leukemia. Blood 122 (2013) develop a therapy by means of specific inhibitors that inhibit the 1761-1769 | doi: 10.1182/ blood-2013-01-476473 growth signal.
Further authors from Helmholtz Zentrum München: is the most common cancer of Harald Polzer, Tobias Herold, Acute myeloid leukemia (AML) Sebastian Vosberg, Stefan K. the hematopoietic system occurring in adults. Only about 25 to 30 Bohlander, Karsten Spieker- percent of the patients survive the first five years after diagnosis. mann – Clinical cooperation group Pathogenesis of Acute Myeloid Leukemia HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 84 85
BRIEF PROFILE PROF. DR. DIRK EICK Head of the research unit Further Decryption of Molecular Epigenetics at the Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Zentrum München the Epigenetic Code 1999–2008: Research group leader at the Institute of Clinical Proteins Molecular Biology and Tumor The central function of the enzyme RNA polymer amino acids repeated 52 times. As Dirk Eick and Genetics ase II is the transcription of genetic information his colleagues have now found, not only are 1983–1989: Postdoc, University Pol II of Freiburg, Habilitation stored in the DNA into mRNA, which then trans- the serine amino acids reversibly modified in Histones with DNA ports this information from the cell nucleus to the CTD by means of phosphorylation, but also the ribosomes and there regulates protein biosyn the amino acids threonine and tyrosine. The thesis. In addition, however, RNA polymerase II – combinatorics of how the large number of these CTD (carboxy as has recently been discovered – is also crucial three amino acids is altered in the RNA polymer- terminal domain) whenever epigenetic information is stored in ase II regulates important flows of information the cell and retrieved again. Scientists of the in the cell and is the central component for the Y S P T S P S research unit Molecular Genetics, together with regulation of gene expression in all multicellular P P colleagues from Ludwig-Maximilians-Universität organisms. The CTD of RNA polymerase II thus München and the Universities of Marseille and has the function of linking genetic and epigenetic Barcelona, have explored important new details information in the cell. This further decryption cABL kinase Polo-like kinase of these mechanisms. of epigenetic mechanisms enables a better With many slight alterations of amino acids, cells understanding of the molecular process of cell are able to store information in the chromatin differentiation, as well as pathological and of the cell, in order to transcribe this later when degenerative developments in the cells. Among needed or to delete it. The RNA polymerase II is other research questions, the scientists want to RNA Polymerase II (POL II) transcribes the information of all protein-coding genes into mRNA and directly involved in this process with its carboxy investigate how certain environmental factors is a central hub for storage and retrieval of epigenetic information in the cell. The carboxy terminal terminal domain (CTD) – a sequence of seven can influence the cells epigenetically. domain (CTD) thus links genetic and epigenetic information.
Original Publications: Corinna Hintermair et al.: Threonine-4 of Mammalian RNA Polymerase II CTD is Targeted by Polo-Like Kinase 3 and Required for Transcription- Scientists of the research unit Molecular Epigenetics, in collab- al Elongation. The EMBO Jour- oration with colleagues from other institutions, have decrypted nal 31 (2012) 2784-2797 | doi: mechanisms that control the cell nucleus enzyme RNA polymerase 10.1038/ emboj.2012.123 II so that selected genetic and epigenetic information is processed. Andreas Mayer et al.: CTD The elucidation of such processes is a basis for better understand- Tyrosine Phosphorylation ing diseases, and for developing new therapeutic approaches. Impairs Termination Factor Recruitment to RNA Polymerase II. Science 336 (2012) 1723 -1725 | doi: 10.1126/science.1219651
The term epigenetics refers to the genomic regulation mech- Further authors from anisms which are not specified in the DNA sequence. Epigenetic Helmholtz Zentrum München: modifications, e.g. the methylation of histone components of the Corinna Hintermair, Martin chromosomes, can contribute to determining the fate of genes and to Heidemann, Rob D. Chapman – Research unit Molecular a certain extent can be passed on to subsequent generations. Epigenetics Andrew Flatley, Elisabeth Kremmer – Institute of Molecu- lar Immunology HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 86 87
BRIEF PROFILE BRIEF PROFILE PD DR. TIM-MATTHIAS STROM DR. CHRISTIAN GIEGER Research group leader at the Intellectual Disability New Insights into the Leader of the research group Institute of Human Genetics, Genetic Epidemiology and Helmholtz Zentrum München KORA-gen, Institute of Genetic Epidemiology, Helmholtz 1992–2001: Physician, Medical Is Caused by Genetic Mechanisms of Zentrum München Genetics, University Hospital of Ludwig-Maximilians- 2010: Paula and Richard von Universität München Hertwig Award for Interdis 1987–1992: Physician, Chil- Spontaneous Mutation Red Blood Cell Formation ciplinary Cooperation dren’s Hospital of Technische since 2004: Research associate Universität München at Helmholtz Zentrum München and project leader of KORA-gen Severe congenital intellectual disability, which is products. In comparison to a control group, they Disturbances in red blood cell formation often and the Netherlands, the research groups led 1999–2004: Researcher in not associated with a known disease syndrome identified in the genomes of the patients a lead to anemia. This is a common condition by Christian Gieger and Janina Ried of the industry and at the Fraunhofer such as Down syndrome, is caused to a high per- significantly higher number of point mutations that can cause cognitive impairment, growth Institute of Genetic Epidemiology, Christine Institute St. Augustin 1994–1998: Research associate centage by new mutations in the genome of the and small insertions and/or deletions. In retardation, and impaired physical capacity. Meisinger of the Institute of Epidemiology II and at Ludwig-Maximilians- child and is not inherited from the parents to the particular, the number of mutations leading to Scientists of the Institutes of Genetic Epidemi- Angela Döring of the Institutes of Epidemiology Universität München child. This is the result of a study by researchers significant damage of the respective protein ology, Epidemiology I, and Epidemiology II I and II studied a total of six parameters of red from the Institute of Human Genetics, Helmholtz was increased. The mutations were found in of Helmholtz Zentrum München have been blood cells, including the number and size of the Zentrum München, which they carried out many different genes, and only in a few genes instrumental in the identification of a total of 75 erythrocytes and the hemoglobin values. Further together with partners from the network ‘Mental did the researchers find new mutations in more independent loci that play an important role in biological analyses provided insights into biolog- Retardation’ in the National Genome Research than one person. The authors of the study human red blood cell formation. For this pur- ical mechanisms and signaling pathways in the network (NGFN) and with researchers from the conclude that a large proportion of severe con- pose, a genome wide association study (GWAS) formation and function of erythrocytes, which Universities of Erlangen, Essen and Zurich. To genital intellectual disability is probably caused was carried out on 135 000 individuals. shall be studied in more detail in future research this end, the scientists studied the genomes of by new mutations. With the aid of exome For 43 of the identified 75 genes, no association projects. These findings may then also contribute 51 patients who were affected by congenital sequencing, intellectual disability will be able with parameters of erythrocytes (red blood cells) to a deeper understanding of genetic abnormal- intellectual disability and the genomes of their to be diagnosed much faster and more easily. had hitherto been detected. The identified genetic ities of blood cells and congenital forms of ane- parents. Tim Strom and Thomas Meitinger of The scientists assume that in the future, the loci contribute to the variance of the properties mia. In subsequent studies, the researchers want the Institute of Human Genetics carried out method will become a standard procedure. The of the erythrocytes in the general population. In to identify genetic factors influencing clinically exome sequencing for the mutation analyses in good news for the affected parents is that in collaboration with research groups from the UK relevant abnormalities of the red blood cells. which selectively the DNA segment was investi- future pregnancies there is only a slight risk of gated that encodes proteins and other functional having a child with an intellectual disability.
Original Publication: Anita Rauch et al.: Range of Congenital intellectual disability, which is not associated with By means of a genome-wide association study (GWAS), researchers Genetic Mutations Associated a known disease syndrome, is often – so the results of exome have identified 75 gene loci that play a role in human red blood cell with Severe Non-Syndromic sequencing – caused by spontaneous mutations in the genome of formation, enabling them to take a closer look at hematological Original Publication: Sporadic Intellectual Disability: Pim van der Harst et al.: Seventy- an Exome Sequencing those affected. Since the mutations are thus not inherited, there is abnormalities such as anemia. Five Genetic Loci Influencing Study. The Lancet 380 (2012) low risk of recurrence in another pregnancy. the Human Red Blood Cell. 1674-82 | doi: 10.1016/S0140- Nature 492 (2012) 369-378 | doi: 6736(12)61480-9 10.1038/nature11677
Further authors from Intellectual disability (ID) affects about two percent of the Genome wide association studies (GWAS) are advanced Further authors from Helmholtz Zentrum München: population. Although most cases have an underlying genetic cause, analysis techniques used to detect genetic differences between Helmholtz Zentrum München: Elisabeth Graf, Thomas to date only a few genetic defects have been identified. healthy subjects and people with conditions such as anemia or Janina S. Ried – Institute of Meitinger, Thomas diabetes. The aim is to identify associations between genetic Genetic Epidemiology Schwarzmayr, Christine Meisinger – Institute variations and external characteristics and thus to identify genetic Thomas Wieland – Institute of of Epidemiology II Human Genetics risk factors for the development or course of a disease. Angela Döring – Institute of Harald Grallert – Research unit Epidemiology I, Institute of Molecular Epidemiology Epidemiology II Christa Meisinger – Institute of Thomas Illig – Research unit Epidemiology II Molecular Epidemiology HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 88 89
BRIEF PROFILE DR. MELANIE WALDENBERGER Leader of the research group DNA Methylation Plays Complex Diseases, Research Unit Molecular Epidemiology Institute of Epidemiology II Important Role in 2003–2012: Research associate at Ludwig-Maximilians- CpG Universität and Helmholtz Human Metabolism 1 methylation 1 variant in CpG site Zentrum München
2 variant in Aging processes, but also environmental and more than 457 000 positions in the DNA to detect coding region lifestyle factors such as smoking or diet cause epigenetic alterations and compared these with 5 biochemical modifications in the DNA during the concentrations of 649 different metabolites. The 3 biochemical course of a lifetime. This can lead to methylation analysis showed that methylation of 28 DNA seg- transformation(s) of the DNA components, whereby methyl groups ments changed a number of important metabolic 4 Concentra Genetic Gene are added without changing the actual DNA processes. tion(s) of 4 variant in gene- sequence. These processes, known as epigenetic In the respective DNA regions, already known variant(s) expression regulatory element metabolites changes, can impact gene function. Scientists disease-associated genes were also found, such of the Institute of Genetic Epidemiology and the as the gene TXNIP, which regulates glucose me- 5 methylation in gene- Research Unit Molecular Epidemiology carried tabolism and is associated with the development 6 regulatory element out an epigenome-wide association study to of diabetes mellitus. Consistent with this finding, determine if there are any associations – and altered concentrations of metabolites of the 6 availability of if so which associations – between epigenetic lipid and glucose metabolism were found in the gene-product processes and health consequences for the methylated TXNIP. Moreover, genes that can be Efficiency of metabolism. For this purpose, the team led by biochemically altered by smoking affect different 2 enzymatic 3 Christian Gieger and Melanie Waldenberger in metabolic activities. reactions collaboration with Karsten Suhre from Weill The study provides new insights into how Cornell Medical College in Qatar analyzed blood lifestyle factors can influence the metabolism Original Publication: Ann-Kristin Petersen et al.: samples of more than 1800 participants of the through DNA alterations. The results will be Epigenetics Meets Metabolom- KORA study (Cooperative Health Research in the used to develop new diagnostic and therapeutic ics: An Epigenome-Wide Augsburg Region). In the samples they analyzed approaches for lifestyle-related diseases. Association Study with Blood Serum Metabolic Traits. Human Molecular Genetics 23 (2014) 534-545 (Epub 2013 Sep 6) | doi: 10.1093/hmg/ddt430 Schematic view of processes through which genetic variance and CpG methylation can be Lifestyle factors can alter DNA and thus have an impact on the influenced in the metabolism. Possible feedback reactions are depicted by dashed lines. metabolism and cause disease. In an epigenome-wide association Further authors from study, scientists of Helmholtz Zentrum München have identified 28 Helmholtz Zentrum München: Ann-Kristin Petersen, Markus DNA alterations that are associated with metabolic changes. Brugger, Konstantin Strauch, – Institute of Genetic Epidemi- ology Sonja Zeilinger, Harald Grallert – Research Unit Molecular Epidemiology Biological functions of organisms are also controlled by higher- Gabi Kastenmüller, Werner level regulatory mechanisms, which are grouped under the term Römisch-Margl, Karsten Suhre – epigenetics. Epigenetic modifications, such as methylation of Institute of Bioinformatics and protein components of chromosomes, can help to determine the Systems Biology fate of genes and are passed on to some extent even to subsequent Annette Peters, Christine Meisinger, Institute of generations. Epidemiology II Jerzy Adamski, Institute of Experimental Genetics – Genome Analysis Center HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 90 91
BRIEF PROFILE BRIEF PROFILE DR. JAN KRUMSIEK PROF. DR. VASILIS NTZIACHRISTOS Leader of the research group Detecting the Identities of Imaging Modalities – Systems Metabolomics, Insti- Institute Director and chair of tute of Computational Biology, Biological and Medical Imaging Helmholtz Zentrum München at Helmholtz Zentrum München “Unknown Metabolites” two better than one and Technische Universität 2013 to the present: Helmholtz München Postdoc Program, Initiative and Networking Fund 2013: Gottfried Wilhelm 2013: Doctoral Award A combined analysis of genetic variants and Research in the Augsburg Region), the scientists Scientists of the Institute of Biological and to observe bone growth, obtain images of Leibniz Prize of the German Technische Universität Research Foundation actual metabolic changes shows relationships detected in the blood the biochemical identity Medical Imaging and the Institute of Experi- subcutaneous tumors in the neck area in high München and Helmholtz 2011: Erwin Schrödinger Prize Doctoral Award between risk factors and the development of of nine previously unknown metabolites and mental Genetics led by Vasilis Ntziachristos have resolution and to diagnose lung cancer. The of the Helmholtz Association 2012: Graduate Students‘ common diseases and thus provides evidence associated 97 compounds to specific metabolic achieved a milestone in imaging diagnostics: By new combination of the two methods enables and the Founders‘ Association Award Helmholtz Zentrum of standardized measurable biomarkers. Thus pathways, including risk factors for high blood combining two established, non-invasive imag- more precise diagnosis as to where the tissue for German Science, Basic München far, however, only such metabolites could be pressure and insulin resistance. A new marker ing techniques – X-ray computed tomography is pathologically changed than when the tech- Science Award of the Academy of Molecular Imaging (AMI) considered that the measuring devices recog- for impaired liver detoxification may in the future (XCT) and a camera-based hybrid fluorescence niques are used individually. 2010: Heinz Maier-Leibnitz BRIEF PROFILE nize. The research team led by Jan Krumsiek and be a chemical derivative of vitamin C whose molecular tomography (FMT) system – they suc- In further steps, the scientists want to refine Medal of Technische DR. GABI KASTENMÜLLER Gabi Kastenmüller of the Institute of Bioinfor- concentration is also genetically influenced. ceeded for the first time in obtaining a 360-de- this in-vivo method so that it can be used in Universität München matics and Systems Biology and the Institute This blood value can indicate to the physician gree view from the inside of a living organism. pre-clinical diagnosis in patients – for example 2008: European Research Leader of the research group of Computational Biology has developed a how effectively the liver detoxifies a patient’s With the combined XCT-FMT method, which in the early detection of tumors. The Institute Council Advanced Investigator Metabolomics at the Institute Award of Bioinformatics and Systems method to also identify unknown metabolites. body and thus aid in the selection of a suitable combines the advantages of the two proven of Biological and Medical Imaging explores in 2002–2007:Assistant Professor, Biology, Helmholtz Zentrum The application of the method on risk factors drug for this particular patient. Personalized imaging techniques, internal structures and vivo imaging technologies for the life sciences. Harvard University Medical München that have not been chemically characterized therapies that are based on a combination of organs can be examined in detail in the living It develops systems, theories and methods for School and Massachusetts until now allows conclusions to be drawn about genetic and biochemical risk factors can offer organism. For example, it is possible – due to imaging and image reconstruction as well as an- General Hospital since 2014: Honorary Lecturer, which processes influence the development of chances of an improvement the quality of life the 360° view – to exactly localize pathologically imal models for the testing of new technologies 2004: Top 100 of the World’s King‘s College London, UK Young Innovators 2009-2011: Postdoc, Institute disease, but also about the individual’s response or a cure of common diseases, such as type 2 altered tissue in vivo. Through the combination on the biological, pre-clinical and clinical level. until 2001: Postdoc, Harvard of Bioinformatics and Systems to drug therapies. On the basis of data from diabetes, which is currently incurable. of the two methods, significantly better results The aim is to provide innovative tools for the bio University Biology the KORA population study (Cooperative Health can be achieved than with a stand-alone medical laboratory, for diagnostics and for the 2010: Guest scientist at method. In living mice the scientists were able monitoring of therapies for human diseases. Metabolon Inc., USA 2009: PhD, Technische Universität München
Original Publication: Jan Krumsiek et al.: Mining the Scientists at the Institute of Bioinformatics and Systems Biology have Scientists of the Institute of Biological and Medical Imaging have Unknown: A Systems Approach developed a method to identify previously unknown metabolites in combined two well-established imaging techniques – X-ray based to Metabolite Identification the blood that may be associated with genetic variations. This could computed tomography and fluorescence molecular tomography – in Original Publication: Combining Genetic and Met- Angelique Ale et al.: FMT-XCT: abolic Information. PLoS Genet- be a further boost for the development of personalized therapies. such a way that a detailed 360-degree view of the inside of a living in Vivo Animal Studies With ics 8 (2012) e1003005 | doi: organism is possible. Hybrid Fluorescence Molecular 10.1371/journal.pgen.1003005 Tomography-X-Ray Computed Tomography. Nature Methods 9 (2012) 615-622 | doi: 10.1038/ Further authors from nmeth.2014 Helmholtz Zentrum München: Metabolomics is the study of the characteristic metabolic traits of In X-ray based computed tomography, different images Karsten Suhre, Brigitte Wägele, an organism that are present in the metabolites of a blood sample. taken with the aid of x-ray are assembled in the computer to provide Werner Römisch-Margl, Fabian The analysis is performed via mass spectrometry or magnetic three-dimensional visualization of the investigated structures. In Further authors from J. Theis – Institute of Bioinfor- resonance imaging. fluorescence tomography the distribution of a fluorescent Helmholtz Zentrum München: matics and Systems Biology Angelique Ale, Vladimir Ermo- substance which was administered prior to the test is shown three- Thomas Illig – Research Unit layev, Eva Herzog – Institute of Molecular Epidemiology dimensionally and non-invasively in the tissue and organs. Biological and Medical Jerzy Adamski – Institute of Imaging Experimental Genetics Christian Cohrs, Martin Hrabe Christian Gieger – Institute of de Angelis – Institute of Genetic Epidemiology Experimental Genetics HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 92 93
BRIEF PROFILE DR. RUI WANG-SATTLER Head of the research group Lifestyle Factors Affect Metabolism, Research Unit Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München Metabolite Profile 2007–2011: Senior scientist, Institute of Epidemiology, Helmholtz Zentrum München Cigarette smoking causes a multitude of changes led by Rui Wang-Sattler, Tao Xu, Jerzy Adamski 2010: Paula and Richard von 10 in metabolite concentration, which increase the and Annette Peters identified 21 smoking- Hertwig Award for Interdis ciplinary Cooperation risk of multiple diseases. When an individual related metabolites, which are enriched in amino Smokers 2000–2007: Postdoc scientist, quits smoking, smoking-related changes in acid and lipid pathways. 19 out of the 21 ornithine European Molecular Biology human serum metabolites are reversible. These metabolites were found to be reversible in 5 Former smokers Laboratory (EMBL) results are consistent with previous findings former smokers, including arginine, glutamate that the risk for cardiovascular disease – such and lyosphosphatidylcholines, which have Never smokers BRIEF PROFILE as a myocardial infarction – reduces after been previously preported to be associated 0 TAO XU smoking cessation. Scientists of the Research with the risk reduction of cardiovascular diseases. Unit Molecular Epidemiology, of the Institute of These results indicate the remarkable bene- 1st study 2nd study Doctoral student, Research Unit Epidemiology II and of the Institute of Experi- fits of smoking cessation and provide a link to 7 years Molecular Epidemiology, Institute of Epidemiology II, mental Genetics analyzed blood samples from cardiovascular disease benefits. Helmholtz Zentrum München more than 1 200 participants of the population- The identified smoking-related metabolites based Cooperative Health Research in the pinpointed disturbed pathways, which are 0.0 Region of Augsburg (KORA) cohort. Blood sam- useful to elucidate further health consequences ples and smoking status of these individuals of nicotine consumption. The study therefore
were collected at two time points: a baseline represents a meaningful metabolomics PC ae C38:6 -0,5 survey conducted between 1999 and 2001 and approach with which the molecular signatures a follow-up after seven years. Overall, through of lifestyle-related environmental exposures the analysis of the metabolite profiles, the team and diseases can be studied. -1
Original Publication: Tao Xu et al.: Effects of Smoking -1,5 and Smoking Cessation on Human Serum Metabolite Profile: Results from the KORA Cohort Study. BMC Medicine 11 1st study 2nd study (2013) 60 | doi: 10.1186/1741- 7 years 7015-11-60 Smoking-related changes in human serum metabolites are revers- ible after smoking cessation, consistent with the known cardiovas- cular risk reduction and other health consequences. Further authors from Helmholtz Zentrum München: Concentrations of the metabolite arginine and ornithine in the blood of smokers, former smokers Christina Holzapfel, Erik Bader, and never smokers: The data of the two studies were collected with an interval of seven years. Zhonghao Yu, Katrin Perstorfer, Marta Jaremek, Thomas Illig – Research Unit Molecular Epidemiology The Cooperative Health Research in the Region of Cornelia Prehn, Jerzy Adamski – Augsburg (KORA) has been studying the health of thousands of Institute of Experimental people from the Augsburg area for almost 30 years. The aim is to Genetics understand the effects of environmental factors, behavior and genes. Werner Roemisch-Margl, The core topics of the KORA studies are questions about the develop- Fabian Theis, Karsten Suhre – ment and course of chronic diseases, in particular heart attack and Institute of Bioinformatics and Systems Biology diabetes mellitus. To this end, research is conducted on risk factors H.-Erich Wichmann – Institute from health behavior, the environment and genetics. of Epidemiology I Karl H. Ladwig, Annette Peters Institute of Epidemiology II HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 94 95
BRIEF PROFILE PROF. DR. DR. FABIAN J. THEIS Director of the Institute of Bioinformatics for Computational Biology, Helmholtz Zentrum München, chair of Mathematical Models of Biological Systems Stem Cell Research of Technische Universität München
2008–2012: Junior group leader Scientists of the Institute of Computational these transcription factors. The pairings could at the Institute of Bioinformat- ERG Biology at Helmholtz Zentrum München, together be correlated positively or negatively with ics and Systems Biology, TEL ETO2 Helmholtz Zentrum München with colleagues from the Stem Cell Institute and characteristic stages of cell maturation and Functional 2010: Starting Grant of the the Institute for Medical Research of the Uni- therefore provided clues about the functions relationships European Research Committee versity of Cambridge, have identified important of the individual transcription factors and the SCL FLI1 (ERC) differentiation pathways of stem cells. The Munich cell fate. Within the expression patterns, the Direct protein- 2008: Habilitation scientists were responsible for the characteriza- scientists also found previously unrecognized 2006–2007: Bernstein Fellow protein interactions at the Bernstein Center for tion of transcriptional networks in blood stem and relationships between the factors Gata2, Gfi1 RUNX1 GATA1 Computational Neuroscience progenitor cells using high-throughput single-cell and Gfi1b. This is of particular importance Göttingen gene expression analysis. because especially for Gata2 and Gfi1, recently 2003–2006: Research stays in Out of a pool of nearly 600 single primary blood a correlation has been described with leukemia: Japan, USA, Finland stem and progenitor cells isolated from mouse Gata2 is thought to promote the formation of bone marrow, 18 transcription factors were malignant cell clones, whereas Gfi1 plays a PU.1 GATA2 BRIEF PROFILE identified which can cause a further differenti- more protective role. DR. FLORIAN BÜTTNER ation of the progenitor stem cells. Transcription The reconstruction of individual transcription factors are responsible for turning gene ex- factor profiles and the identification of their Leader of the research group Machine Learning, Institute pression “on” or “off”. By means of a statistical networks offer the opportunity not only to NFE2 GFI1 of Computational Biology, mapping technique known as dimensionality understand the physiological differentiation Helmholtz Zentrum München reduction, Florian Büttner and Fabian Theis and development of cells, but to better under- identified specific patterns in the pairings of stand degenerative and malignant processes. 2011–2012: Postdoc at the Institute of Bioinformatics and MITF GFI1B Systems Biology, Helmholtz Zentrum München 2007–2011: Assistant, The Institute of Cancer Research, University of London MEIS1 HHEX
LYL1 LDB1 In collaboration with the University of Cambridge, scientists of the LMO2 Institute of Computational Biology have identified important differen- tiation pathways of stem cells by means of expression patterns of transcription factors. Network of 18 transcription factors involved in the differentiation of bone marrow stem cells into various blood and immune cells
Cell differentiation is regulated by a complex interaction of external influences on the internal cell environment, in which Original Publication: so-called transcription factor-regulated-networks are of particular Victoria Moignard et al.: importance. Transcription factors are responsible for activating or Characterization of Transcrip- repressing gene expression. tional Networks in Blood Stem and Progenitor Cells Using High-Throughput Single-Cell Gene Expression Analysis. Nature Cell Biology 15 (2013) 363-372 | doi: 10.1038/ncb2709 HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 96 97
BRIEF PROFILE DR. KLAUS MAYER Head of the Department Mapping of the Casting Light on the Genome and Systems Biology of Plants, Helmholtz Zentrum München Barley and Bread Evolution of Nightshades 1999–2012: Research group leader at the Institute of Bioinformatics and Systems Biology Wheat Genomes The Tomato Genome Consortium (TGC), a group vegetable plants – both with regard to its eco- 1997–1999: Research associate of more than 300 scientists from 14 countries, nomic significance and the quantity produced. at the Munich Institute for Protein Sequences (MIPS), has sequenced the genome of the domesticated Members of the Solanaceae family are used as the Max Planck Institute of In the framework of the International Barley The findings are seen as an important basis to tomato and its closest wild relative (Solanum food, spices and as medicinal plants. The new Biochemistry, Munich Sequencing Consortium, scientists at the accelerate the breeding of barley varieties that pimpinellifolium). Together with other research sequences provide a reference to identify impor- 1993–1997: Research assistant, Helmholtz Zentrum München have made a e.g. show improved resistance or are better centers in Germany, Helmholtz Zentrum München tant genes in related species.The sequences also Ludwig-Maximilians-Universität München and the University of major contribution to deciphering and ana- adapted to climate change. At the same time, the was involved in the bioinformatics analysis and open up insights into the diversification of the Tübingen lyzing the barley genome and to develop new barley genome served the researchers as model annotation of the genome sequences. tomato and the adaptation to new environmental approaches for molecular breeding. for the more complex bread wheat genome. The research group led by Klaus Mayer at the conditions. The research of the International Barley Se- Here the team headed by Klaus Mayer, together Department of Plant Genome and Systems Biology They reveal that 60 million years ago tripli- quencing Consortium, which along with other with British scientists from the Universities of was responsible for data management, database cation of the tomato genome occurred. After partners, includes scientists led by Klaus Mayer Bristol und Liverpool and the John Innes Centre infrastructure and dissemination as well as gene that, a large part of the triplicated genes were at the Department of Plant Genome and Systems carried out and published a first genome analy- family and comparative genome analyses. The lost. However, some exist even until today and Biology, provides a detailed view into the barley sis. Along with rice and corn, wheat is the most sequences provide the most detailed insights to control the most important breeding traits of genome. For the first time a high-resolution important cereal crop. The bread wheat genome date into the tomato genome. Thus, the approx- the tomato including strength, fleshiness and genome overview was created for a genome that is hexaploid (contains six copies) and contains imately 35 000 genes of the tomato with their fruit coloring. by far exceeds the size of the human genome. approximately 96 000 genes. Due to its size and genomic position and a large portion of their The results are an important basis for further In addition, the team was able to gain insight complexity, it has not yet been fully sequenced. likely functions are now known. research to optimize the production of toma- into gene regulation and make comparisons The now published genome gene atlas is an The tomato is a member of the Solanaceae toes and other crops. The resistance to pests, between wild barley and cultivated strains. important step towards understanding the or nightshade family. The Solanaceae family diseases and drought, which in part have been Thus, an in-depth molecular understanding interplay of the different genome copies of this includes potatoes, bell peppers and eggplant. lost during the domestication of the plant, is of of the inventory of cereal genomes and a first cereal and to enable molecular breeding even Worldwide, it is the most important family of particular importance. glimpse into molecular circuits was obtained. for wheat.
Original Publication: The International Barley Sequencing Consortium, Klaus Mayer et al.: A Physical, Together with international partners, a team of the Department of With the participation of Helmholtz Zentrum München, the Tomato Genetic and Functional Sequence Plant Genome and Systems Biology has created ordered sequence Genome Consortium, a group of more than 300 scientists from 14 Assembly of the Barley resources of the highly complex genomes of barley and bread wheat. countries, has sequenced the tomato genome with its approximately Genome. Nature 491 (2012) 711- 716 | doi: 10.1038/nature11543 Both crops are of enormous importance. 35 000 genes. The Department of Plant Genome and Systems Biology Original Publication: manages a range of several plant genome databases, provided The Tomato Genome Consorti- Rachel Brenchley et al.: Analy- important infrastructure for the data management and carried out um: The Tomato Genome sis of the Bread Wheat Genome gene family and comparative genome analyses. Sequence Provides Insights into Using Whole-Genome Shotgun Fleshy Fruit Evolution. Nature Sequencing. Nature 491 (2012) 485 (2012) 635-641 | doi: 705-710 | doi: 10.1038/na- Barley is one of the earliest domesticated and most important cereal 10.1038/nature11119 ture11650 crops. The barley genome is diploid, contains slightly more than 26 000 genes and includes 5.1 billion base pairs (5.1 Gb). The bread In gene sequence annotation, the position of exons and introns, wheat genome, with 17 billion base pairs (17 Gb), is not only protein-encoding regions including the encoded protein and its Further authors from Further authors from Helmholtz Zentrum München: much larger but also contains considerably more genes – approx- possible functions, promoter elements and repetitive DNA elements is Helmholtz Zentrum München: Manuel Spannagl, Heidrun Thomas Nussbaumer, Heidrun imately 96 000. A wheat cell is hexaploid and has six copies of its attached (annotated) to the actual DNA sequence. Gundlach, Remy Bruggman – Gundlach, Mihaela Martis, chromosomes. Institute of Bioinformatics Manuel Spannagl, Matthias and Systems Biology/Munich Pfeifer – Department Plant Information Center for Protein Genome and Systems Biology Sequences (MIPS) HIGHLIGHTS 2012/2013 HIGHLIGHTS 2012/2013 98 99
BRIEF PROFILE PD DR. ANTON R. SCHÄFFNER Research group leader, How Roots Branch Out Institute of Biochemical Plant Pathology, Helmholtz Zentrum München
1996: Habilitation Plants initiate lateral root formation deep with- Agronomique in Montpellier, France, and the 1990–1997: Research in the primary root. For lateral roots to reach Universidad de Extremadura, Badajoz, Spain. group leader, Institute of the soil, they first must break through the rigid, Researchers at Helmholtz Zentrum München Biochemistry, Gene Center overlying tissue layers of the primary root. investigated in particular the phenotypes of of Ludwig-Maximilians- To initiate lateral root emergence, the plant plants whose aquaporin expression had been Universität München hormone auxin is required. This also stimu- genetically modified and determined the tempo- lates processes to weaken the cell walls. In the ral and spatial expression patterns of aquaporins current study, it was found that the increased in the emerging lateral root. The colleagues in Longitudinal section auxin concentration also causes aquaporin France contributed essential physiological data. of a root expression to change in the cell membranes Mathematical modeling based on the experi- of the new organ and the surrounding tis- mentally found expression patterns was also sue. Aquaporins facilitate water movement crucial; it enabled enabled the British partners across the cell membranes of plant cells. This to correctly predict the phenotypic findings. The regulation is also critical for how rapidly the consortium’s insights gained on the model plant newly initiated lateral roots can penetrate the Arabidopsis thaliana (thale cress), may be useful tissue. The researchers led by Anton Schäffner for plant breeding: Through the formation of at the Institute of Biochemical Plant Pathology lateral roots, plants not only have a better grip have conducted research on this topic together in the soil but can also absorb more water and with colleagues from the Centre for Integrative minerals. This is a great advantage for plant Plant Biology of the University of Nottingham in growth – especially with reduced water avail- the UK, the Institut Nationale de la Recherche ability in soils due to climate change.
Experimental system for lateral root formation: Lateral roots are specifically induced at the bend of the primary root, which is formed due to the changed direction of gravity after a 90° rotation of the plants. Thus, a synchronous development of the new organ can be achieved, which progresses through eight stages, as is depicted in the root longitudinal sections.
The expression of aquaporins is locally regulated by the increased auxin levels that initiate lateral root formation. These changes significantly affect the rate of lateral root emergence.
Original Publication: Benjamin Péret et al.: Auxin Regulates Aquaporin Function to Facilitate Lateral Root Emer- Aquaporins are proteins in the cell membrane of organisms that gence. Nature Cell Biology 14 regulate water permeability. Thus, they also influence the rate of (2012) 991-1006 | doi: 10.1038/ pressure changes within plant cells driving their expansion growth. ncb2573
Further authors from Helmholtz Zentrum München: Jin Zhao, Olivier Da Ines – Institute of Biochemical Plant Pathology Innovation and Translation To identify new target structures for drugs after bone marrow transplantation by adoptive Innovation management and the management of translational and clinical against diabetes, a strategic research collabora- T-cell transfer was recently completed and is projects at Helmholtz Zentrum München are dedicated to promote the tion was launched in 2013 between the Institute being evaluated. Further projects in or shortly improvement of health. They support the development of patient-oriented for Diabetes and Obesity and Sanofi Aventis prior to clinical trials include cell vaccination Deutschland GmbH. The research collaboration is in acute myeloid leukemia, NK-cell transfer in research towards concepts for clinical applications and drug development. initially designed to last for three years. non-small cell lung cancer and prophylactic CMV and EBV-specific T-cell transfer after stem cell Translational Research transplantation. Translational research, which aims at the benefit Since 2013, two clinical cooperation groups have for patients, is an essential element of the been participating in observational studies of Helmholtz Zentrum München turns promising Trianta Immunotherapies GmbH was founded in scientific strategy at the Center. The objective the German Center for Diabetes Research (DZD). scientific approaches from basic research into 2013 as a spin-off of the Institute of Molecular is to enable the reliable stratification of patient For the Prediabetes Lifestyle Intervention Study innovations. It ensures that all innovative know- Immunology and develops immunotherapies for groups and to develop preventive and treatment PLIS, these groups investigate whether lifestyle how being produced at the Center is protected the treatment of cancer. For its spin-off project, approaches tailored to the individual patient. changes with respect to diet and physical activity by patents and out-licensed for commerciali- the team led by Institute Director Prof. Dr. Key success factors are the close connection positively influence the risk for the development zation. Insights from basic research are further Dolores Schendel received an m4 award of the between excellent basic research, continuous of type 2 diabetes. Within the German Diabetes developed and applied in spin-offs and in collab- Bavarian Ministry of Economic Affairs endowed advancements in platform technologies and dif- Study DDS, a differentiated long-term obser- orations with competent industrial partners. with 500 000 euros. ferentiated model systems with large population vation of newly diagnosed diabetes patients is cohorts, and clearly defined patient populations. being carried out. In 2012 and 2013, four new companies were Dosimetrics GmbH was also founded in 2013. The The Center implements this principle in three In cooperation with the Department of Radiation launched as spin-offs from Helmholtz Zentrum company is a manufacturer and service provider translational centers, eleven clinical cooperation Oncology, Ludwig-Maximilians-Universi- München. Thus, the Center translates excellent of personal dose monitoring systems for ionizing groups and a translational project portfolio in tät München, the clinical cooperation group science into specific applications and creates radiation. Based on the research of the personal collaboration with clinical partners. "Personalized Radiotherapy in Head and Neck new impetus in the field of data management, dosimetry service at Helmholtz Zentrum München, Cancer" was established in 2013. It analyzes clinical imaging, immunotherapy and radiation the largest personal dosimetry service in Europe, Translational Centers molecular markers for predicting the efficacy of dosimetry. Dosimetrics provides technologies for easy detec- There are three regional translational centers radiotherapy for tumors of the head and neck area. tion and the rapid readouts of individual doses. in the fields of lung, diabetes and allergy Clueda AG, founded in 2012, is a software research that closely combine basic research, Translational Project Portfolio company that brings intelligent prediction, With the new start-up companies, Helmholtz technology platforms and clinical research in a To specifically strengthen the development of analysis and decision support tools to market Zentrum München has continued its successful long-term perspective. While both the Diabetes personalized preventive, diagnostic and therapeu- maturity for different industries. In 2013 the series of spin-offs. Since 1997, 18 spin-off com- Study Center and the Munich Allergy Research tic concepts, translational and have been funded company received the Best in Big Data Award panies from the Center have been founded. 15 Center collaborate with Technische Universität since 2012. A total of nine peer-reviewed projects of the weekly magazine Computerwoche for of these are currently active on the market and München, translational research in cooperation were supported by 2013. an analysis system it developed together with employ approximately 400 people. with Ludwig-Maximilians-Universität München a German investment bank. and the Asklepios Fachkliniken München-Gauting Cross-Program Initiative Personalized Medicine In the field of drug development, Helmholtz has been implemented at the Comprehensive In the newly established Helmholtz Initiative The start-up company SurgVision B.V., launched Zentrum München specifically promotes projects Pneumology Center since 2103, following the Personalized Medicine (iMed), the Center has in 2013, develops systems that enable molec- that are in the early phase of the value added successful appointment of the Chair of Clinical teamed up with four Helmholtz Health Research ular live imaging during surgical procedures. chain. The portfolio currently comprises devel- Pneumology at the University Hospital. Centers to establish a research-driven and A first clinical study on image-guided surgical opmental projects from the areas of diabetes, molecular systems medicine program which procedures for breast cancer patients is nearing neurodegeneration, autoimmune diseases and Clinical Cooperation Groups spans various indications. The initiative provides completion, additional indications are being cancer. The major aim is the identification and In eleven clinical cooperation groups, defined high-throughput and IT platforms for collab- evaluated. development of innovative drugs. Five of the 27 clinical-scientific hypotheses are elucidated with orative projects. The indications are cancer, SurgVision developed from a collaborative newly registered patents in 2012 and 2013 the aim of achieving clinical proof of concept. metabolic and cardiovascular diseases, diseases project between the Institute of Biological and refer to new compounds. The entire patent Four of them develop personalized cellular of the nervous system as well as lung diseases Medical Imaging and the University Medical portfolio of the Center currently covers 150 therapy approaches for clinical application. A and infectious diseases. Center Groningen, the Netherlands. patent families. phase I/II trial for treatment of CMV infection Innovation and 18 Translation Spin-Offs from the Center since 1997
Here we present two promising new approaches for prevention and therapy. INNOVATION AND TRANSLATION INNOVATION AND TRANSLATION 104 105
BRIEF PROFILE Many years of intensive preparatory work, coupled with determination and the necessary PROF. DR. DANIEL Antipsychotic Drugs Tested bit of luck led to this success. Since 2008, Daniel Krappmann, head of the research unit KRAPPMANN Cellular Signal Integration at the Institute of Molecular Toxicology and Pharmacology at Helmholtz Zentrum München, has been investigating the MALT1 protease, which he had Head of the research unit Cellular Signal Integration and recognized as a particularly interesting enzyme. “It is the only enzyme in this class in deputy director of the Institute against Malignant Lymphomas humans, and is thus very exclusive,” the 45-year-old biologist said. He not only analyzed of Molecular Toxicology, its enzymatic effectiveness, but using genetic methods, also explored the effects of the Helmholtz Zentrum München For Daniel Krappmann, in retrospect everything seems so clear and obvious. In view MALT1 protease on the immune system. In addition, his team, together with scientists from Technische Universität München, was able to show that aggressive lymphoma cells since 2014: of their groundbreaking findings, the excitement was palpable among Krappmann and Professor, are not viable without the activity of MALT1. his 15-member team until the study was published: The researchers discovered that Ludwig-Maximilians- Universität München specific drugs used since the 1950s to treat psychotic disorders can also be used as cancer After all this was known, Krappmann decided to look for compounds that can inhibit treatment against malignant lymphomas. The substances inhibit the enzyme MALT1 MALT1, since such substances would provide good starting points for drugs for the treat- 2011-2013: leading to the death of cancer cells. This could mean a breakthrough in cancer research. ment of lymphomas or autoimmune diseases. His doctoral candidate Daniel Nagel took on Funding through Helmholtz Validation Fund Grant the task and tested 18 000 substances in cooperation with the Leibniz-Institut für Mole- kulare Pharmakologie in Berlin. After many test runs and further analyses in cooperation since 2008: with Charité Universitätsmedizin Berlin, it became apparent that the long-known antipsy- Privatdozent, chotic drugs mepazine and thioridazine were among the best MALT1 inhibitors. Ludwig-Maximilians- Universität Munich
"It is a huge advantage that both drugs have long been in clinical use," said Krappmann. 2005-2008: "Many side effects have been extensively studied, and this allows us to quickly initiate Research group leader, clinical trials." These will now begin parallel to further trials that will be carried out on Institute of Toxicology, the effect of the substances in autoimmune diseases. Helmholtz Zentrum München 2005: Habilitation
According to Krappmann, Helmholtz Zentrum München offers excellent conditions 2002 -2005: for such research. Here researchers find expertise in a variety of disciplines, from Junior research group leader, biochemistry and immune research to preclinical testing. Meanwhile, a separate Max Delbrück Center, Berlin screening unit has been established for drug discovery at the Center. 1997-2002: Postdoc, Max Delbrück Center, Added to this was the financial support from the Helmholtz Validation Grant, the new Berlin funding instrument of the Helmholtz Association. The funding for the project amounted to around 950 000 euros, half of which came from the Helmholtz Association and the other half from Helmholtz Zentrum München. The financial support from this fund shall enable scientists from Helmholtz centers to develop their project ideas into commercial results within two years. That is exactly what happened in Krappmann’s project.
The successful identification of a MALT1 inhibitor will also raise the awareness of the pharmaceutical industry for developments and projects within the Helmholtz Association and, over the medium term, significantly promote strategic partnerships. Thus, innovative solutions for patients and even personalized medicine approaches will become possible: Publications: “In the future, special biomarkers may enable the identification of patients who respond to Daniel Nagel et al.: Pharmaco- treatment with a MALT 1 inhibitor,” said Daniel Krappmann. “Our long-term goal is quite logic Inhibition of MALT1 clear – to replace standard treatment with personalized treatment, i.e. with a treatment Protease by Phenothiazines as a Therapeutic Approach for protocol designed for the individual patient.” the Treatment of Aggressive ABC-DLBCL. Cancer Cell 22 All in all, a great success for Innovation Management at Helmholtz Zentrum München. (2012) 825–837 | doi: 10.1016/j. Here in an exemplary way, basic research findings are translated into applications – thus ccr.2012.11.002 increasing the value creation of the Center immensely. “It is only possible to pursue such Florian Schlauderer et al.: research approaches consistently in an interdisciplinary research environment,” Krapp Daniel Krappmann is studying the MALT 1 protease enzyme as new approach for Structural Analysis of Phenothi- the treatment of malignant lymphomas. With support from the Helmholtz Validation mann said. “With our study we have shown that it really can be done!“ azine Derivatives as Allosteric Grant and the Department of Innovation Management, the team of the research unit Inhibitors of the MALT1 Cellular Signal Integration led by Krappmann found potential enzyme inhibitors, Paracaspase. Angew. Chem. which then were licensed for therapeutic further development. Image: signaling Int. Ed. 52, 10384–10387 (2013) | doi: 10.1002/anie.201304290 protein visualized with an immunofluorescence microscope. INNOVATION AND TRANSLATION INNOVATION AND TRANSLATION 106 107
BRIEF PROFILE At the Institute of Diabetes Research at Helmholtz Zentrum München, scientists under the DR. FLORIAN HAUPT Spearhead of direction of Anette-Gabriele Ziegler are seeking to find the causes of type 1 diabetes, to elucidate the disease course and to combat the disease. Type 1 diabetes – in contrast to Trial coordinator of the the much more frequent type 2 diabetes – is triggered by an autoimmune process. As a diabetes trials INIT II and TEENDIAB and research result of genetic alterations or environmental influences, the insulin-producing cells – the associate at the Institute of Diabetes Prevention beta cells in the pancreas – are destroyed. Often children and adolescents are affected. Diabetes Research, Helmholtz When approximately 80 percent of these cells have failed, there is a dramatic rise in Zentrum München The incidence of a disease is rising, and no one knows why: For years doctors have blood glucose levels leading to the outbreak of the disease. Without insulin treatment, the outcome of the disease would be fatal. 2011-2012: observed that the number of cases of type 1 diabetes in children – especially young Research associate, children – and adolescents is rising throughout the world. In Germany, the rate of Ludwig-Maximilians- The physician Ruth Chmiel and the biologist Florian Haupt are working at the Institute Universität München new cases is currently increasing by three to five percent annually. The causes for of Diabetes Research to develop a vaccine against the dangerous disease. “By detect- this increase are still unknown; possible culprits may be environmental factors that ing certain antibodies in the blood we can diagnose the dysregulation of the immune 2011: have an effect in the womb or in early childhood, for example early nutrition, viral system, which ultimately leads to the outbreak of the disease, at an early stage,” said PhD degree, Visiting Scientist, SYKE Finnish Environment infections or changes in the immune system through improved hygiene, but also the Ruth Chmiel. “Practically all individuals in whom two or more of these antibodies Institute, Helsinki development of the microbiome of the digestive system in early childhood and the have been detected develop type 1 diabetes within 15 to 20 years after diagnosis. If detected early, there is still time for preventive immunotherapy.” 2009-2011: bacterial colonization of the intestine. Case Manager for Vascular Within the framework of the Intranasal Insulin Trial (INIT II) and the Oral Insulin Trial, Surgery, Kliniken Südostbayern, Klinikum Traunstein the two scientists select appropriate German candidates who can participate in the trial of such a vaccine. Whoever has close relatives with type 1 diabetes and in whose blood the characteristic autoantibodies can be detected can take part in the trial. BRIEF PROFILE The subjects take one capsule with insulin daily or are treated with intranasal insulin RUTH CHMIEL spray once a week. “The immune system of the body can thus gradually get used to Trial physician and research the insulin,” explained Chmiel. “It acts directly on the nasal mucosa and in this way associate at the Institute of does not disturb the metabolism.” Diabetes Research, Helmholtz Zentrum München First successes of the vaccine have already been confirmed: Evaluations of a trial in the U.S. have shown that through the oral administration of insulin in young children 2009-2012: Dissertation, Institute of and in individuals with high autoantibody titers, the onset of diabetes can be delayed Diabetes Research, Helmholtz significantly. Zentrum München and Research Group Diabetes, The trials in Munich will be accompanied by projects that address fundamental questions. Klinikum rechts der Isar, Tech- nische Universität München “In translational projects at Helmholtz Zentrum München, we are studying how changes in the metabolism affect the development of type 1 diabetes,“ said Florian Haupt. “In addition, cells of the immune system are being analyzed to elucidate the underlying disease processes.” Helmholtz Zentrum München is now right at the interface of basic research and the translation of the findings into medical practice. The Institute of Diabetes Research is, so-to-speak, the spearhead of diabetes research in Germany. Publications: Stefanie Krause et al.: IA-2 Autoantibody Affinity in Children at Risk for Type 1 Diabetes. Clinical Immunology 145 (2012) 224–229 | doi: 10.1016/j. clim.2012.09.010
Jennifer Raab et al.: Continuous Rise of Insulin Resistance Before and After the Onset of Puberty in Children at Increased Risk for Type 1 Diabetes – a The physician Ruth Chmiel and the biologist Florian Haupt explore new avenues for Cross-Sectional Analysis. the prevention of type 1 diabetes. Through the oral and intranasal administration of Diabetes Metab Res Rev. insulin (in the image: insulin crystals) they are seeking to delay the onset of type 1 29(2013)631-635 | doi: 10.1002/ dmrr.2438 diabetes in risk patients. Talent Management
RGE T GROUP
TA S
Talented scientists and outstanding staff are elemental to the success of
Helmholtz Zentrum München. Excellent researchers and competent staff in
science management and in the administration and technical infrastructure
require a strategic human resources management. This includes human
resources development which is systematically oriented on the needs of
various target groups and on the Center’s strategy.
Individual
Team
qualifying
workshops
measures
Continuing
HUMAN RESOURCES Training
education and
DEVELOPMENT programs training
The focus of Human Resources Development at in and adjusted to particular organizational
Helmholtz Zentrum München is on the promo- units, such as project and time management
tion of young scientists and high potentials, or systematic personnel selection. Individual
especially in the areas of professional, methodo- training courses and support for managers and
logical, social and leadership skills. potential executives were also expanded. In this
It is complemented by a wide range of continuing context the implementation of an internal devel-
education and training courses. Both levels take opmental program for managers and manage-
into account the increasing complexity of today’s ment trainees plays an important role.
research, which takes place in an international
environment in cross-linked infrastructures. Based on individual advisory consultations,
Mentoring Coaching external training programs are also offered In 2012 and 2013, human resources development and arranged. For the qualification of science
activities at the Center increased dynamically managers and administrators the training
due to the consistent orientation towards needs program of the Center for Science Management and demand. More than 150 internal training (ZWM) in Speyer and the Helmholtz Manage-
events are held per year. Besides scientific topics, ment Academy are especially suitable.
language and computer courses and training in
management and social skills are predominant. Coaching and differentiated mentoring programs S T E R AT T U R supplement the portfolio of effective develop- E G Y F H E F U Furthermore, in the past two years, more than ment measures. These include – in addition O R T 70 moderated team workshops were held under to the individual support provided by Human supervision of Human Resources Development. Resources Development – offers of the Helmholtz The workshops mainly focused on leadership Association such as the mentoring program and cooperation topics as well as changes in for young women in science, the shadowing processes, structures, roles and responsibilities. program for employees in the administrative- The team approach was also applied to specific technical area and a cross-company mentoring training topics that have to be implemented program in the Munich region. Continuing Education and 3400 Training participants in seminars and training courses
As examples, we present two participants in the “Munich Leadership Development in Science” program, which Helmholtz Zentrum München helped to initiate. TALENT MANAGEMENT TALENT MANAGEMENT 112 113
Recruiting and “Professionalism, leadership and management skills as well as social competence are the four important qualities that characterize good science managers.” Uwe Bott Promoting Talent in Science Administration
BRIEF PROFILE Science is not created in a vacuum, quite the contrary: Funds have to be BARBARA FERWAGNER acquired and managed; laboratories must be operated and services
Barbara Ferwagner is project organized; scientists and specialists in various fields have to be recruited coordinator in the Department and hired. Only if the framework conditions are suitable, can researchers of Operations & Support. From 2011 to the beginning of 2014 utilize their capabilities in an optimal way. That is why efficient management is she was assistant to the CFO. needed. “In a research center such as ours, the administration must navigate She came to Helmholtz Zentrum between world-class science with high dynamics on the one hand and the München in 2004, where she first was financial and project relatively rigid requirements of the public service sector on the other,” said management assistant at the Uwe Bott, who heads Human Resources Development at Helmholtz Zentrum Institute of Experimental Genet- ics. Barbara Ferwagner studied München. Both sides have to be taken into account: the researchers who want business engineering at the to remain as flexible as possible and who want to avoid spending too much University of Applied Sciences Munich. time on administrative tasks, and the administrators who often must comply with rigid official structures and who are not particularly well paid.
However, to be successful in international com- institutions in the Munich region, who already project management, budgeting, and employee course must cover many aspects.” Her goal is BRIEF PROFILE DR. UWE BOTT petition, new processes and structures must have or will soon have budget and staff respon- motivation, among other topics. Barbara to make it as easy as possible for the scientists be developed, and there is a special need for sibility.” Ferwagner finds the concept of the course con- and to largely relieve them of administrative Dr. Uwe Bott heads the De- science managers who are keen in solving very One of the participants of the course, Barbara vincing, since the basic principles of a variety of duties. “We are establishing a new adminis partment of Human Resources specific problems in this area. “At Helmholtz Ferwagner, has been working since March in the skills are taught. trative structure at Helmholtz Zentrum Development at Helmholtz Zentrum München. He studied Zentrum München we have established a number Department of Operations & Support. In her pre- In addition to the qualification in management München for this purpose to ensure that each education, psychology and of options in which employees can take part vious positions at Helmholtz Zentrum München responsibilities, her colleague Theresia institute has a primary contact person who sports science at the Univer- in continuing education and training courses she was able to gain experience in a number of Schmitt, who has been working as project coordinates all the further details.” sity of Düsseldorf, completed and develop further in this area,” said Bott. different areas. “In order to qualify for leader coordinator since 2011 in the Department of Uwe Bott underlines how important it is to his doctorate and worked “We offer around 150 Center-internal training ship roles, it is necessary to step out once from Operations and Support, sees a significant have transparent processes and to avoid and conducted research in the treatment and training of events, which in part are intensive courses on the microcosm of one’s own center and to added value of the ZWM program in building having different people responsible for the chronically ill patients. From management topics such as scientific project discuss similar issues with colleagues from other networks at the science location Munich. Her same topics. “That is why good science 1999 to 2011 Uwe Bott was BRIEF PROFILE management. There are also seminars and academic institutions,” she said. “There are so supervisor recommended her for the program managers are so essential,” he said. “The four responsible for Human THERESIA SCHMITT workshops in which employees acquire specific many different cultures and ways of organizing and – just as for Barbara Ferwagner – Helm- aspects – professionalism, leadership and Resources Development at knowledge and skills and practice the transfer of science administration. This exchange with other holtz Zentrum München assumes the costs; the management skills as well as social compe- the German Aerospace Theresia Schmitt has worked Center (DLR). learning objectives into daily work. Our center colleagues represents a great added value of the participants themselves must devote the nec- tence – must be covered already in the training since 2011 as project coor- dinator in the Department also participates in the Helmholtz Management program.” In principle, the challenges are always essary time by means of holidays or flextime. phase. Once this requirement profile is clearly of Operations & Support. Academy, whose purpose is to promote under the same: leading people, managing resources, The thirty-two year-old business graduate with defined, it is easier to select the appropriate Prior to that she worked for standing between science and the administration. developing strategies, communicating and a specialization in health economics likes the executives and to give them systematic training.” three years as a business In addition, we have intensified our cooperation implementing, balancing interests, organizing interdisciplinary work: “In science management consultant. Theresia Schmitt with the Center for Science Management (ZWM) majorities, making and carrying out decisions. at our center many aspects intertwine: business studied business administra- tion at Ludwig-Maximilians- Speyer; since October, five of our employees The day to day work requires from leaders a wide administration, medical and legal topics as well Universität München and spent have been participating in the one-year range of management skills and the ability to as topics of company consulting such as process one semester at the Università program ‘Munich Leadership Development in relate these to the special characteristics of sci- optimization or organizational structures. That Commerciale Luigi Bocconi in Science’. It is aimed at academic and adminis- ence management. The ZWM program therefore is exciting and varied. Every day you can deal Milan. trative leaders from universities and research offers modules on leadership and self-leadership, with something new, which is why the training Facts & Figures 2234 2012/2013 employees
More than three fourths of the employees are science staff. The proportion of women in leadership positions is 51 percent at the research group and junior research group level. FACTS & FIGURES 2012/2013 FACTS & FIGURES 2012/2013 116 117
Scientists’ disciplines Biology
Staff Mathematics 1 % 4 % Computer Science Helmholtz Zentrum München is an attractive employer for a broad spectrum 4 % Agricultural Science/ of science-oriented professions. The Center’s dynamic development and 2 % its international work environment make it an interesting place to work 8 % Forestry 3 % both for renowned researchers and for novice scientists and administrators. Epidemiology/Health 40 % Science In 2012, Helmholtz Zentrum München employed the compatibility of work and family both for Geology/ a total of 2148 people from 65 different countries. men and women in equal measure, child care 8 % Environmental Science In 2013 the number of employees increased to options for employees' children on the research 2234; the percentage of employees financed via campus are continually being expanded. Engineering third-party funding dropped from 29 percent to In 2012 and 2013 women made up 59 percent of 25 percent. Over three quarters of the staff work the workforce. The overall proportion of women Physics/Biophysics in the scientific area; in 2012 these included 330 in leadership positions is 34 percent; 51 percent 15 % doctoral students, 186 postdocs and 503 scien- of the research groups and junior research Chemistry/Biochemistry tists. In 2013 the scientific staff was made up groups are headed by women. of 328 doctoral students, 200 postdocs and 535 No MINT Subjects scientists. Research activities focus on the areas Vocational Training of biology, biochemistry, physics and medicine. In addition to the promotion of young scientists, 15 % 8 % Helmholtz Zentrum München is engaged in Equal Opportunities vocational training and offers a broad spectrum 1 % Medicine Helmholtz Zentrum München views equal oppor- of vocational training disciplines. At the end tunities for men and women to be an integral part of 2012 there were 61 vocational trainees; at the 6 % Veterinary Medicine of its corporate culture. It promotes the careers of end of 2013 there were 63 trainees in commer- women employees and creates equal framework cial and technical vocations as well as future Other conditions for professional success. To improve animal keepers. Disciplines
Women in Leadership Positions Distribution of staff by area of work
76 % Percentage of women in leadership 34 % 13 % Science positions 5113 % 49 % 66 % Infrastructure Percentage of women 11 % as leaders of research Administration groups or junior research groups
As of: December 31, 2013 FACTS & FIGURES 2012/2013 FACTS & FIGURES 2012/2013 118 119 Finances 2012 Institutional funding 2012
15.1 million In 2012, the overall budget of Helmholtz Zentrum München amounted to euros approximately 211 million euros, with 165 million euros coming from Personnel costs 16.5 million institutional funding provided by the Federal Government and the Free State euros Material costs of Bavaria at a ratio of 90:10. External funds from national and international 69.1 research grants amounted to 45.9 million euros, including the funds that Costs for third-party were forwarded to third parties. 21.8 million million subsidies euros euros Ongoing investments
42.8 Construction and million procurements euros > 2.5 million euros
Total financing and funding sources 2012 External funding according to source 2012
0.8 million euros Institutional funds from Federal Government the Federal Government project funding 5.3 Institutional million State Government euros funds from the Free 45.9 project funding State of Bavaria million 12.0 euros million German Research Third-party funds 6.7 million euros Foundation (DFG) euros Helmholtz Association 16.5 million euros Other national sources 148.8 4.3 million 0.6 million euros euros Federal bureaus million 9.0 million euros EU euros 4.8 million euros Funds forwarded
Industry (international)
0.4 million euros 2.0 million euros Contract research FACTS & FIGURES 2012/2013 FACTS & FIGURES 2012/2013 120 121 Finances 2013 Institutional funding 2013
15.0 million In 2013, the overall budget of Helmholtz Zentrum München amounted to 11.4 euros million approximately 224 million euros, with 172 million euros coming from euros Personnel costs institutional funding provided by the Federal Government and the Free State Material costs of Bavaria at a ratio of 90:10. External funds from national and international 75.8 research grants amounted to 51.7 million euros, including the funds that 23.2 million million Costs for third-party were forwarded to third parties. euros euros subsidies Ongoing investments 46.8 million Construction and euros procurements > 2.5 million euros
Total financing and funding sources 2013 External funding according to source 2013 Federal Government 1.1 million euros project funding Institutional funds from the Federal Government 0.8 million euros State Government project funding Institutional 6.7 million 10.0 funds from the Free 51.7 euros 0.7 million euros German Research State of Bavaria million million Foundation (DFG) euros euros Third-party funds Helmholtz Association
3.5 million Other national sources 17.2 million 12.6 euros euros 155.0 million Federal bureaus euros 5.4 million million euros EU
euros Funds forwarded
8.3 million Industry (international) euros 2.0 million euros 0.6 million euros Contract research
Business operations FACTS & FIGURES 2012/2013 FACTS & FIGURES 2012/2013 122 123 Project Funding and Research Cooperations
Helmholtz Zentrum München successfully takes part in in calls for proposals In 2013 Dr. Martin Elsner and Dr. Tillmann Through its participation in programs of the by the Federal Ministry of Education and Research, the European Research Lüders each received an ERC Consolidator Federal Ministry of Education and Research Framework Programme, the German Research Foundation (DFG), the Grant. The two research group leaders at the (BMBF), Helmholtz Zentrum München makes Institute of Groundwater Ecology are to receive significant contributions to current issues of Helmholtz Association of German Research Centres and other public and a total of 3.85 million euros funded by the great social and economic importance. The private organizations. In 2012 the acquired third-party funding amounted European Research Council for their research. Center was thus able to solicit considerable to 39.2 million euros, and in 2013 the amount was 39.1 million euros. research funds in 2012 and 2013. Particularly Prof. Dr. Magdalena Götz, director of the noteworthy are the German Plant Phenotyping Institute of Stem Cell Research and Chair of Network (DPPN) with 6.1 million euros in fund- Physiological Genomics at Ludwig-Maximil- ing and two competence networks on radiation In public funding for Helmholtz Zentrum Helmholtz Zentrum München was particularly ians-Universität, received an ERC Advanced research coordinated by the Center, together München, the Federal Government ranks first successful in acquiring grants from the European Grant endowed with 2.38 million euros for her amounting to 2.1 million euros. with approximately 12 million euros per year, Research Council (ERC). The Center has a total research on molecular mechanisms regulating followed by the European Union with almost of 12 ERC grantees with a funding volume of neurogenesis. The grant for Magdalena Götz The BMBF research network on photonics 9 million euros and the German Research 15.9 million euros and thus assumes a leading is one of the few Advanced Grants awarded “Ultrasensitive detection and manipulation Foundation (DFG) with more than 4 million euros. position among the Helmholtz Centres. to German women researchers in 2013: From of cells and/or tissues and their molecular At the end of 2013 there were more than 350 Researchers at the Center who apply for grants 2400 submitted project proposals, 37 male components” is coordinated by Helmholtz third-party agreements for research funding. receive intensive coaching and support from and only 4 female Principal Investigators from Zentrum München. From the BMBF funding staff members of the Department of Program Germany were awarded a grant. initiative “e:Med – Measures to Establish Systems By the end of 2013, Helmholtz Zentrum München Planning and Management. Medicine” the Center receives 2.0 million euros contributed to almost 430 proposals in the 7th While the average success rate for Starting Scientists of Helmholtz Zentrum München were for its research contributions on heart attack, Research Framework Programme of the Euro- Grants and Consolidator Grants is 13.9 percent extraordinarily successful in the last call for stomach cancer, neurodegeneration and alcohol pean Union. This resulted in 113 projects with in the EU, Helmholtz Zentrum München received proposals on the topic of Health within the 7th addiction. Within the framework of the 2nd fund- approximately 63 million euros in funds from the nine grants for a total of 34 proposals – a Research Framework Programme. From nine ing phase of the BMBF Competence Networks on EU for the Center. success rate of 26.5 percent. proposals submitted by the Center in the second Obesity and Diabetes, the Center receives a total phase, six projects were approved with a total of 0.8 million euros in funds. The German Center funding volume of more than 3 million euros. for Infectious Disease Research (DZIF) forwards 2.7 million euros in funding to Helmholtz ERC Grants at Helmholtz Zentrum München For his contributions to German-French Zentrum München for its research projects. cooperation in the field of pneumology, Oliver Eickelberg was awarded the Gay Lussac-Hum- Significant projects supported byresearch Number Funding [in millions of euros] boldt Research Award 2013. Under his leader- foundations include the Max Eder Junior ship, the Helmholtz-INSERM-Alliance for the Research Group “Therapeutic Inhibition of Auto- Starting Grants 7 9.02 Cure of Chronic Lung Disease was founded, crine Signals in Breast Cancer Stem Cells” led by [brought to the Center] 1 0.53 which evolved from an initiative of the research Dr. Christina Scheel, which is funded by the ministries of both countries. German Cancer Aid with 0.7 million euros, and a Consolidator Grants 2 3.85 network on Parkinson research coordinated by the Center, which is led by Dr. Christian Johannes Advanced Grants 1 2.38 Gloeckner; this network is funded by the Michael [as cooperation partner] 1 0.08 J. Fox-Foundation with 0.5 million U.S. dollars.
Total: 12 15.9 FACTS & FIGURES 2012/2013 FACTS & FIGURES 2012/2013 124 125
Helmholtz Zentrum München has close contacts For Helmholtz Zentrum München, projects In 2012 and 2013 a total of 20 new projects were approved with the two Munich universities and the funded by the German Research Foundation by the Initiative and Networking Fund (IVF) of the Helmholtz Max Planck Institutes of Biochemistry and of comprise an important component of the Neurobiology. The success of this cooperation is externally funded research activities. This Association of German Research Centres: shown in nine Collaborative Research Centres/ especially applies to young, outstanding junior Transregios of the German Research Foundation research group leaders, who are funded (DFG), in which Helmholtz Zentrum München through the Emmy Noether Program of the The Helmholtz Alliance ICEMED (Imaging and Curing Environmental Metabolic Diseases), coor participates with 34 subprojects. Along with DFG. In 2012/2013 the Center established three dinated by Prof. Dr. Matthias Tschöp and including 18 partners, is being funded with a total Berlin, Munich plays a prominent role as cluster new junior research groups with a total volume of 15 million euros until 2017. Of these funds, four million euros are to remain at Helmholtz location for the life sciences in Germany. of more than 4.5 million euros through this Zentrum München. funding program.
The Center is a partner in the Helmholtz Alliance Preclinical Comprehensive Cancer Center (PCCC), in the Helmholtz Alliance Remote Sensing and Earth System Dynamics and the special project Synthetic Biology, altogether funded with 0.8 million euros. Participation of Helmholtz Zentrum München in DFG-funded projects 2012/2013 The Helmholtz Research School of Radiation Sciences (RS2) receives funding amounting to 1.8 million euros. Funding program Projects Four new Helmholtz Young Investigator Groups are to receive 625 000 euros each over five years. 7 Collaborative Research Centres and 2 Transregios 34
In the framework of the Helmholtz Postdoctoral Program, three projects are to receive 100 000 10 priority programs 13 euros each over three years, and two additional projects from the research field Health are to receive 150 000 euros each. 7 research groups 7
Within the framework of the W2/W3 program for women professors, Dr. Irmela Jeremias has Leibniz Prize 1 received a W2 position to conduct research on “Diseases of the Immune System – Personalized Medicine Targeting Leukemia Stem Cells”. Junior research groups in the Emmy Noether Program 3
Two Helmholtz International Research Groups at the Institute of Diabetes Research and the Individual grants 39 Institute of Lung Biology are being funded with 280 000 euros.
As part of the Helmholtz-Alberta Initiative “Infectious Diseases Research”, the Institute of Virology under the direction of Prof. Dr. Ulrike Protzer has been awarded 0.2 million euros for research projects. International Cooperation Two of the Helmholtz International Fellow Awards, which are endowed with 20 000 euros each and were awarded for the first time in 2013, went to cooperation partners of Helmholtz In 2012/2013, Helmholtz Zentrum München Canada, China and Japan. Within Europe, Center Zentrum München: Prof. Dr. Harald von Boehmer of Harvard Medical School in Boston, and participated in approximately 1200 internation- scientists collaborate particularly often with Prof. Dr. Naftali Kaminski of the University of Pittsburgh. al scientific collaborations with universities, scientists from the UK, France, Italy, Austria, the non-university research institutions and indus- Netherlands, Switzerland and Spain. Dr. Jan Krumsiek, Institute of Computational Biology, has received the Helmholtz Doctoral try partners in over 60 countries. A special element of the Center’s international Student Award in the research field Health, which is endowed with 5000 euros. These partnerships may, but need not necessar- activities is the Helmholtz-Israel cooperation ily have a contractual basis. In 2013, there were on personalized medicine, which was launched more than 270 cases of international funding or in 2013 and in which Helmholtz Zentrum cooperation agreements, often with multiple München and four other biomedical Helmholtz partners. centers and scientific institutions in Israel have International cooperation serves the exchange joined together. The objective of the long-term between scientists on the basis of guest stays cooperation is to develop new strategies for and collaborative research or publications. personalized medicine in the field of diagnosis, The U.S. tops the list by far in the number of treatment and prevention of widespread common non-European cooperative projects, followed by diseases such as diabetes. 39 Organization Scientific Institutes and Research Units
In the fields of Environmental and Radiation Sciences, eleven institutes and research units have joined to form departments; five institutes comprise the Helmholtz Diabetes Center. ORGANIZATION ORGANIZATION 128 129
Chronic Lung Diseases and Allergies TOPIC 3 Institutes and Research Units INSTITUTE OF EPIDEMIOLOGY (EPI I) INSTITUTE OF LUNG BIOLOGY (iLBD) INSTITUTE OF ALLERGY RESEARCH (IAF) Director (acting): Dr. Joachim Director: Prof. Dr. Oliver Eickelberg Heinrich oliver.eickelberg@ Director: Prof. Dr. Carsten TOPIC 1 Systemic Analysis of Genetic and Environmental Factors with an Impact on Health [email protected] helmholtz-muenchen.de Schmidt-Weber T 089 3187 4150 T 089 3187 4666 schmidt-weber@ Chair of Experimental Pneumology helmholtz-muenchen.de INSTITUTE OF EPIDEMIOLOGY II INSTITUTE OF EXPERIMENTAL INSTITUTE OF HUMAN GENETICS at LMU T 089 3187 3081 (EPI II) GENETICS (IEG) (IHG) Chair of Molecular Allergology and Environmental Research at TUM Director: Prof. Dr. Annette Peters – also Topic 2 – Director: Prof. Dr. Thomas Meitinger [email protected] Director: Prof. Dr. Martin Hrabe de [email protected] T 089 3187 4566 Angelis T 089 3187 3294 Mechanisms of Genetic and Environmental Influences on Health and Diseases TOPIC 4 [email protected] Chair of Human Genetics at TUM T 089 3187 3502 INSTITUTE OF GENETIC Chair of Experimental Genetics at INSTITUTE OF STEM CELL RESEARCH UNIT CELLULAR SIGNAL INSTITUTE OF VIROLOGY (VIRO) EPIDEMIOLOGY (IGE) TUM INSTITUTE OF DEVELOPMENTAL RESEARCH (ISF) INTEGRATION (AZS) GENETICS (IDG) Director: Prof. Dr. Ulrike Protzer Director: Prof. Dr. Konstantin Strauch Director: Prof. Dr. Magdalena Götz Head: Prof. Dr. Daniel Krappmann [email protected] [email protected] GENOME ANALYSIS CENTER (GAC) – also Topic 4 – magdalena.goetz@ daniel.krappmann@ T 089 3187 3004 T 089 3187 2838 Director: Prof. Dr. Wolfgang Wurst helmholtz-muenchen.de helmholtz-muenchen.de Chair of Virology at TUM Chair of Genetic Epidemiology at LMU Service platform [email protected] T 089 3187 3750 T 089 3187 3461 Head: Prof. Dr. Jerzy Adamski T 089 3187 4110 Chair of Physiological Genomics RESEARCH UNIT GENE VECTORS [email protected] Chair of Developmental Genetics at at LMU (AGV) RESEARCH UNIT MOLECULAR T 089 3187 3155 TUM INSTITUTE OF CLINICAL MOLECULAR EPIDEMIOLOGY (AME) BIOLOGY AND TUMOR GENETICS Head: Prof. Dr. Wolfgang Hammerschmidt RESEARCH UNIT SENSORY BIOLOGY (KMOLBI) hammerschmidt@ Head: Dr. Christian Gieger RESEARCH UNIT COMPARATIVE AND ORGANOGENESIS (SBO) helmholtz-muenchen.de christian.gieger@ MEDICINE (AVM) Director (acting): Prof. Dr. Wolfgang T 089 3187 1506 helmholtz-muenchen.de Head: Dr. Hernan Lopez-Schier Hammerschmidt T 089 3187 4106 Head: PD Dr. Markus Brielmeier hernan.lopez-schier@ hammerschmidt@ DEPARTMENT OF RADIATION SCIENCES [email protected] helmholtz-muenchen.de helmholtz-muenchen.de T 089 3187 2837 T 089 3187 2187 T 089 3187 1506 Speaker: Dr. Peter Jacob
RESEARCH UNIT MEDICAL RADIATION INSTITUTE OF PATHOLOGY (PATH) RESEARCH UNIT MOLECULAR PHYSICS AND DIAGNOSTICS (AMSD) Diabetes: Pathophysiology, Prevention and Therapy EPIGENETICS (MEG) TOPIC 2 Director: Prof. Dr. Heinz Höfler Head: Prof. Dr. Christoph Hoeschen [email protected] Head: Prof. Dr. Dirk Eick christoph.hoeschen@ T 089 4140 4161 [email protected] helmholtz-muenchen.de HELMHOLTZ DIABETES CENTER (HDC) INSTITUTE FOR DIABETES AND INSTITUTE OF DIABETES RESEARCH Chair of General Pathology and T 089 3187 1512 T 089 3187 4560 OBESITY (IDO) AND METABOLIC DISEASES OF Pathological Anatomy at TUM Speaker: Prof. Dr. Matthias Tschöp HELMHOLTZ ZENTRUM MÜNCHEN AT INSTITUTE OF RADIATION BIOLOGY (ISB) Director: Prof. Dr. Matthias Tschöp THE UNIVERSITY OF TÜBINGEN (IDM) INSTITUTE OF MOLECULAR matthias.tschoep@ RESEARCH UNIT ANALYTICAL IMMUNOLOGY (IMI) Director: Prof. Dr. Michael Atkinson INSTITUTE OF DIABETES helmholtz-muenchen.de Director: Prof. Dr. Hans-Ulrich Häring PATHOLOGY (AAP) [email protected] RESEARCH (IDF) T 089 3187 2103 hans-ulrich.haering@ Director (acting): T 089 3187 2983 Chair of Metabolic Diseases at TUM med.uni-tuebingen.de Head: Prof. Dr. Axel Karl Walch Prof. Dr. Ralph Mocikat Chair of Radiation Biology at TUM Director: Prof. Dr. Anette-Gabriele T 07071 298 2735 [email protected] [email protected] Ziegler Medical Director, University Hospital T 089 3187 2739 T 089 3187 1301 INSTITUTE OF RADIATION anette-g.ziegler@ INSTITUTE OF DIABETES AND Tübingen, Medical Department IV PROTECTION (ISS) helmholtz-muenchen.de REGENERATION RESEARCH (IDR) T 089 3187 3405 INSTITUTE OF MOLECULAR TOXICOL- RESEARCH UNIT MOLECULAR Director (acting): Dr. Peter Jacob Chair of Diabetes and Gestational Director: Prof. Dr. Heiko Lickert OGY AND PHARMACOLOGY (TOXI) IMMUNE REGULATION (AMIR) [email protected] Diabetes at TUM [email protected] T 089 3187 4020 T 089 3187 3760 Director: Prof. Dr. Martin Göttlicher Head: Dr. Vigo Heissmeyer Chair of Diabetes Research/Beta Cell martin.goettlicher@ vigo.heissmeyer@ RESEARCH UNIT RADIATION Biology at TUM helmholtz-muenchen.de helmholtz-muenchen.de CYTOGENETICS (ZYTO) T 089 3187 2446 T 089 3187 1214 Chair of Toxicology and Head: Prof. Dr. Horst Zitzelsberger Environmental Hygiene at TUM [email protected] T 089 3187 3421 ORGANIZATION ORGANIZATION 130 131 Institutes and Research Units Translational Centers and Clinical Cooperation Groups TREATMENT CENTER FOR DIABETES CLINICAL COOPERATION GROUPS Innate Immunity in Tumor Biology PREVENTION STUDIES PATHOMECHANISMS AND Head: Prof. Dr. Gabriele Multhoff THERAPEUTIC TARGETS gabriele.multhoff@ Head: Prof. Dr. Anette-Gabriele helmholtz-muenchen.de TOPIC 5 New Technologies for Biomedical Discoveries Ziegler Pathogenesis of Acute Myeloid T 089 4140 4514 anette-g.ziegler@ Leukemia Institute of Pathology; Clinical partner: helmholtz-muenchen.de Head: Prof. Dr. Wolfgang Department of Radiotherapy and INSTITUTE OF STRUCTURAL BIOLOGY Chair of Genome-oriented Bioinfor- RESEARCH UNIT SCIENTIFIC T 089 3187 3405 Hiddemann Radiooncology at TUM (STB) matics at TUM COMPUTING (ASC) wolfgang.hiddemann@ helmholtz-muenchen.de Immune Oncology Director: Prof. Dr. Michael Sattler Head: PD Dr. Wolfgang Graf zu Castell- COMPREHENSIVE PNEUMOLOGY T 089 7095 2551 Head: Dr. Andreas Moosmann [email protected] RESEARCH UNIT PLANT GENOME Rüdenhausen CENTER (CPC) Institute of Clinical Molecular Biology andreas.moosmann@ T 089 289 13867 AND SYSTEMS BIOLOGY (PGSB) [email protected] and Tumor Genetics; Clinical partner: helmholtz-muenchen.de Chair of Biomolecular NMR-Spectros- T 089 3187 2946 Scientific Director: Prof. Dr. Oliver Dept. of Internal Medicine III at LMU; T 089 3187 1231 copy at TUM Head: Dr. Klaus Mayer Eickelberg University Hospital Munich, Gross- Research Unit Gene Vectors, Clinical [email protected] oliver.eickelberg@ hadern Campus partner: Dept. of Internal Medicine III T 089 3187 3584 INSTITUTE OF HEALTH ECONOMICS helmholtz-muenchen.de of LMU; University Hospital Munich, INSTITUTE OF BIOLOGICAL AND AND HEALTH CARE MANAGEMENT T 089 3187 4666 Osteosarcoma Grosshadern Campus MEDICAL IMAGING (IBMI) (IGM) Institute of Lung Biology; Clinical Head: PD Dr. Michaela Nathrath INSTITUTE OF COMPUTATIONAL partners: University Hospital Munich, michaela.nathrath@ Immunotherapy Director: Prof. Dr. Vasilis Ntziachristos BIOLOGY (ICB) Director: Prof. Dr. Reiner Leidl Asklepios Specialist Hospital, helmholtz-muenchen.de Head: PD Dr. Marion Subklewe v.ntziachristos@ [email protected] Munich-Gauting T 089 3187 2312 marion.subklewe@ helmholtz-muenchen.de Director: Prof. Dr. Dr. Fabian Theis T 089 3187 4168 Institute of Pathology; Clinical partner: helmholtz-muenchen.de T 089 3187 3852 [email protected] Chair of Health Economics and Health Children's Hospital and Polyclinic for T 089 3187 1412 Chair of Biological Imaging at TUM T 089 3187 4159 Care Management at LMU MUNICH ALLERGY RESEARCH Children's and Youth Medicine, TUM Institute of Molecular Immunology; Chair of Mathematical Modeling of CENTER (MARC) Klinikum Schwabing StKM GmbH Clinical partner: Dept. of Internal Biological Systems at TUM Medicine III of LMU; University Hospi- INSTITUTE OF BIOINFORMATICS AND DEPARTMENT OF PROTEIN ANALYTICS Head: Prof. Dr. Carsten tal Munich, Grosshadern Campus SYSTEMS BIOLOGY (IBIS) (PROT) Schmidt-Weber CLINICAL COOPERATION GROUPS schmidt-weber@ INNOVATIVE THERAPIES Personalized Radiotherapy Director: Prof. Dr. Hans-Werner Mewes Head: Prof. Dr. Marius Ueffing helmholtz-muenchen.de Head: Dr. Anna Friedl [email protected] marius.ueffing@ 089 4140 3081 Pediatric Tumor Immunology [email protected] 089 3187 3580 helmholtz-muenchen.de Institute of Allergy Research; Head: Prof. Dr. Uta Behrends T 089 3187 2447 T 089 3187 3567 Clinical partners: Dept. of uta.behrends@ Research Unit Radiation Cytogenetics; Dermatology and Allergology at TUM, helmholtz-muenchen.de Clinical partner: Dept. of Radiation ZAUM – Center for Allergy and Envi- T 089 3068 3076 Therapy and Radiooncology of LMU; Helmholtz Research Program Terrestrial Environment ronment Institute of Clinical Molecular Biology University Hospital Munich and Tumor Genetics; Clinical partner: Children's Hospital and Polyclinic for Platform Immune Monitoring DEPARTMENT OF ENVIRONMENTAL COOPERATION GROUP COMPREHEN- RESEARCH UNIT MICROBE-PLANT CLINICAL COOPERATION GROUPS Children's and Youth Medicine,TUM Head: Prof. Dr. Dolores Schendel SCIENCES (DES) SIVE MOLECULAR ANALYTICS (CMA) INTERACTIONS (AMP) DIABETES Klinikum Schwabing StKM GmbH [email protected] T 089 3187 1301 Speaker: Prof. Dr. Jörg Durner Head: Prof. Dr. Ralf Zimmermann Head: Prof. Dr. Anton Hartmann Subclassification of Type 2 Diabetes Antigen-Specific Immunotherapy Institute of Molecular Immunology; ralf.zimmermann@ anton.hartmann@ and Risk Estimation by Metabolic and Head: Prof. Dr. Dirk Busch Clinical partner: Dept. of Internal INSTITUTE OF BIOCHEMICAL helmholtz-muenchen.de helmholtz-muenchen.de Genetic Marker Profiles [email protected] Medicine III of LMU; University Hospi- PLANT PATHOLOGY (BIOP) T 089 3187 4544 T 089 3187 4109 Head: Prof. Dr. Jochen Seißler T 089 4140 4120 tal Munich, Grosshadern Campus jochen.seissler@ nstitute of Virology; Director: Prof. Dr. Jörg Durner INSTITUTE OF SOIL ECOLOGY RESEARCH UNIT ANALYTICAL BIOGE- helmholtz-muenchen.de Clinical partner: Institute of Medical [email protected] OCHEMISTRY (BGC) T 089 3187 3502 Microbiology, Immunology and T 089 3187 3434 Director: Prof. Dr. Jean Charles Munch Institute of Experimental Genetics; Hygiene at TUM Chair of Biochemical Plant [email protected] Head: PD Dr. Philippe Clinical partners: University Hospital Pathology at TUM T 089 3187 4064 Schmitt-Kopplin Munich, City Campus Chair of Soil Ecology at TUM schmitt-kopplin@ helmholtz-muenchen.de Interaction of Diet and Genetics in RESEARCH UNIT ENVIRONMENTAL INSTITUTE OF GROUNDWATER T 089 3187 3246 Type 2 Diabetes Mellitus SIMULATION (EUS) ECOLOGY (IGOE) Leitung: Prof. Dr. Hans Hauner RESEARCH UNIT ENVIRONMENTAL [email protected] Head: Prof. Dr. Jörg-Peter Schnitzler Director: Prof. Dr. Rainer Meckenstock GENOMICS (EGEN) T 089 3187 3502 [email protected] rainer.meckenstock@ Institute of Experimental Genetics; T 089 3187 2413 helmholtz-muenchen.de Head: Prof. Dr. Michael Schloter Clinical partner: Else-Kröner- T 089 3187 2561 [email protected] Fresenius Center for Nutritional Chair of Groundwater Ecology at TUM T 089 3187 2304 Medicine, TUM ORGANIZATION 132 Organization
Helmholtz Zentrum München is a research institution of the Federal Government and the Free State of Bavaria. The partners are the Federal Republic of Germany, represented by the Federal Minister of Education and Research, and the Free State of Bavaria, represented by the Bavarian State Minister of Finance, Regional Development and Regional Identity.
The bodies of the company are the Assembly of Partners, the Supervisory Board and the Board of Directors. The Scientific Advisory Board, which is made up of external members, advises Helmholtz Zentrum München on scientific issues. Scientists are represented in the Management Committee by the program and topic speakers. The Scientific Review Committee as expert body also advises the Board of Directors on important scientific matters.
Members of the Board of Directors
Prof. Dr. Günther Wess Dr. Nikolaus Blum CEO CFO
Dr. Alfons Enhsen CTO
Members of the Supervisory Board
Chair MinR Dr. Christian Greipl MinDir’in Bärbel Brumme-Bothe Federal Ministry for the Environment, Nature Federal Ministry of Education and Research Conservation and Nuclear Safety
Vice Chair MinR Ulrich Reithmann MDirig. Dr. Ronald Mertz Bavarian State Ministry of Finance, Regional Bavarian State Ministry of Economic Affairs and Development and Regional Identity Media, Energy and Technology
MinR’in Maria Becker Federal Ministry of Health
As of June 2014/ Within the framework of the new Partnership Agreement, changes in the composition of the Supervisory Board are being made. Members of the Scientific Advisory Board
Chair Professor Stephanie J. London Professor Hillel Koren National Institute of Environmental Environmental Health, LLC Durham, Health Sciences, Research Triangle Park, North North Carolina, USA Carolina, USA
Vice Chair Dr. Manfred Rösner Professor Steve Brown mroe-consulting, Eppstein, Germany MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, UK Professor Sisko Salomaa STUK, Radiation and Nuclear Safety Authority, Professor Amnon Altman Research and Environmental Surveillance, Head, Division of Cell Biology, La Jolla Institute Helsinki, Finland for Allergy & Immunology, California, USA Professor Christine Foyer Professor Elizabeth Fisher Centre for Plant Sciences, University of Leeds, UK UCL Institute of Neurology, London, UK Professor Bernhard Wehrli Professor Edda Klipp ETH Zurich, Institute of Biogeochemistry and Humboldt-Universität zu Berlin, Department of Pollutant Dynamics, Switzerland Biology, Germany Professor Stephen C. Woods Professor Geoff J. Laurent Department of Psychiatry, University of Centre for Cell Therapy and Regenerative Medi- Cincinnati, Ohio, USA cine, University of Western Australia, Nedlands, Australia
Professor Edward H. Leiter The Jackson Laboratory, Bar Harbor, Maine, USA
Professor Urban Lendahl Department of Cell and Molecular Biology (CMB), Karolinska Institutet, Stockholm, Sweden IMPRINT
Published by: Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH)
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Editors and Authors: Sonja Opitz, Cordula Klemm, Sonja Duggen, Dr. Nadja Becker, Corporate Communications Dr. Hans Guldner, Dr. Brigitte Röthlein [email protected]
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The Helmholtz Association of German Research Centres is Germany’s largest scientific research organization. Altogether, 36 000 people currently work in its 18 scientific-technical and biological-medical research centers. The Association’s annual budget amounts to more than 3.8 billion euros.
The mission of the Helmholtz Association is research to make a major contribution to solving grand challenges which face society, science and industry. To succeed in meeting these responsibilities, the Association concentrates its work in six research fields: Energy, Earth and Environment, Health, Aeronautics, Space and Transport, Key Technologies and Structure of Matter.
For each of these fields, scientists develop research programs which are evaluated by international experts. Their evaluation forms the basis for the program-oriented funding given to Helmholtz research. Within the six research fields, Helmholtz scientists cooperate with each other and with external partners – working across disciplinary, organizational and national borders. Helmholtz Zentrum München German Research Center for Environmental Health (GmbH)
Ingolstädter Landstrasse 1 D-85764 Neuherberg Germany
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