Annual Report 2006 - Helmholtz Zentrum München · 2007-10-18 · Following Radiation Exposure ......

Annual Report 2006

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General information 2 Table of Contents

4 Preface

6 Chronicle: Looking Back at 2006

13 Structural and Development Plan

18 Clinical Cooperation Groups

19 Patents and Technology Transfer (PTT) Ascenion GmbH

20 Scientifi c Highlights

42 Translational Research

48 General Development

58 Asse Research Mine, Remlingen

59 Organisation Chart

60 GSF in Figures

62 Institutes / Addresses

63 Publications

64 Map

Scientifi c Highlights

Environmental Factors and Health

20 Hereditary Factors Modify Risk of Bone Tumour Following Radiation Exposure

21 Additional Mechanism of Action Found for Oxymetazoline

22 Reduction of Radiation Exposure in CT Angiography

23 Identifi cation of a New Mutation Enhances the Prevention of Inherited Tumours

24 Air Pollutants as a Cause of Middle Ear Infections

25 New Risk Factor for Obesity Discovered

26 New Insights Into a Signal Pathway of the Immune Response

Publisher:

GSF-Forschungszentrum für

Umwelt und Gesundheit, GmbH

in der Helmholtz-Gemeinschaft

(GSF-National Research Center for

Environment and Health

in the Helmholtz Association)

Ingolstädter Landstraße 185764 Neuherberg, GermanyTelephone: +49 - 89 / 31 87-0Telefax: +49 - 89 / 31 87-33 24e-mail: [email protected]: http://www.gsf.de

© GSF München 2007

Editors:

Monika Wiedemann, Michael van den Heuvel,Heinz-J. Haury

Graphical concept:

ADV Mediendienste, Augsburg

Typesetting, litho and

graphical adaptation:

ADV Mediendienste, Augsburg

Printed by:

Schoder Druck, Gersthofen/Augsburg

ISSN 0941-3847

Excerpts from the articles in this publication may be reproduced without further permission, provided that the institute concerned and the GSF are mentioned in the publication. We ask for a copy. All other rights are reserved.

Printed on chlorine-free bleached paper.

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Mechanistic Principles of Health and Disease

27 GSF Owns One of the Largest Libraries of Mutant Mouse Embryonic Stem Cells Worldwide

28 Switch for Self-renewal of Neural Stem Cells Discovered

29 New Genes Discovered for Hereditary Forms of Rickets

30 Protein Designability and Disease

31 Discovery of a Key Molecule for the Development of Dopaminergic Neurons

32 Identifi cation of a New Causal Gene for Cardiac Arrhythmias

33 Genes on Demand. International Initiative for Mutation of the Mouse Genome

34 “Genome Archaeology”: Evolutionary Changes of Genome Structures in Plants

Infection and Immunity

35 Identifi cation of Viral Glycoproteins as Functionally Important Antigens

36 DNA Repair Mechanisms Optimise One Path in Immune Defence

37 B-Cell Transformation by Epstein-Barr Virus: Molecular Steps Elucidated in a B-Cell Lymphoma Model

Ecosystems and Health

38 Principle of Resistance to Mildew in Barley Can Be Transferred to Other Plants

39 New Key Organisms in the Nitrogen Cycle

40 Bacteria and Plants in Dialogue – New Insights

41 Innovative Environmental Analysis with Antibodies

Translational Research42 Adoptive T Cell Therapy: New Perspectives for

Translational Research

44 Fighting Cancer with the Immune System

46 New Vaccination Strategy for the Prevention of Infections in Chronic Pulmonary Diseases

Cover image:

The cover image shows a lateral view of the head of a zebrafi sh embryo (Danio rerio) two days after fertilization. The nucleus and the cytoplasmic membrane of every cell were labeled using fl uorescent dyes. An optical section of the head was captured by laser scanning confocal microscopy. Such fl uorescent stainings reveal the details of the cellular architecture of the brain and the sensory organs. For example, they display the ordered cellular arrangement in the retina, the midbrain, hindbrain or the developing ear not readily visible in normally colorless zebrafi sh embryos.

Biological images are often of great aesthetics beyond their scientifi c content depicting the cellular choreography of developing life. To emphasize this art of embryogenesis the original picture was used for a montage inspired by Andy Warhol’s work. Such artistic versions are aimed at sharing the pleasure scientists fi nd in their work with the nonscientifi c audience. Similar images capturing specifi c moments from zebrafi sh embryonic development have been on display at art exhibitions at the Santa Barbara Museum of Art and the Gallery of the Graduate Center of the City University of New York.

Annual Report 2006

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n 2006, the GSF concentrated on sharpening its profi le, making its objectives clearer and redefi ning

its vision. In doing so we were able to rely on the outstanding research work we have done in recent years, and it was important to us to gather suggestions from all scientifi c levels and to discuss them openly both internally and externally. A very special vote of thanks goes out to everyone involved in this process, especially the members of the Scientifi c and Technical Board

for their often time-consuming but always expedient dialogue with us. The great dedication of everyone involved enabled us to formulate targets that everybody supports.

The GSF contributes to the foundation of Future Medicine and Health Care an explores environ-mental infl uences on human health. The focus of our scientifi c work is the question of how genetic predis-position, the biological system and environmental factors interact. We aim to elucidate the molecular mechanisms of environment-related ailments such as allergies and pulmonary conditions, to investigate effects of fi ne dust and aerosols, to examine the response of tumours to therapy and to gain a better under-

I

Professor Dr. Günther Wess Dr. Nikolaus Blum

PrefacePreface

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standing of the ecosystemic struc-ture of natural resources, such as plants, water and soil.

Translational research has been an important centre of attention in our scientifi c programme for many years. By expanding and improving the structure of the Clinical Coope-ration Groups we have added to our competencies in this fi eld while also further intensifying our already excellent cooperation with Munich‘s universities. This has helped us to refl ect many laboratory results in the clinical environment even more quickly and take clinical results back to the laboratory. Some of these exceptional pieces of work are presented in this report.

In the year under review the GSF was once again very successful at raising third-party funds. We are well above the average approval rate for EU projects.

We have continued unerringly on our path of promoting young scientists, particularly young woman scientists. This began with a doubling of kindergarten capa-cities, continued with the establish-ment of special female junior research groups and went all the way to the EU-funded “Pallas Athene” project for young woman scientists.

Political consulting has always been another important pillar of the GSF. Here too we have great successes to report such as the EU Fine Dust Directive that we helped initiate and the discussion triggered by us on revising the German radiation protection regulations.

Günther Wess

President and CEO

Nikolaus Blum

COO

In particular we would like to thank the entire GSF staff for their invaluable work, which is of course the basis for our future. We thank the Supervisory Board and the Scientifi c Advisory Board for their constructive and critical coopera-tion, and the Federal Ministry of Education and Research and the Bavarian State Government for providing funds.

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Looking Back at 2006


11 January

Tracking Down Programmed

Cell Death: GSF Junior Research

Group Examines the Mechanisms

of Apoptosis

On 12 January a tumour research group starts its work at the Depart-ment of Gene Vectors of the GSF National Research Center for Environment and Health. Under the leadership of PD Dr. Irmela Jere-mias, the group will investigate the mechanisms of apoptosis or programmed cell death. The junior research group position was specifi cally opened to women as one of the GSF activities for the promotion of young women scientists.

12 January

A Focus on Neural Networks:

Start of a New Junior Research

Group at the GSF

On 15 January a neurobiology research group starts its work at the

Institute of Developmental Genetics of the GSF-National Research Center for Environment and Health. Under the leadership of Dr. Andrea Huber Broesamle the group will investigate the mechanisms of the growth of axons, or nerve fi bres. The junior research group position was specifi cally opened to women as one of the GSF activities for the promotion of young women scientists.

18 January

GSF Takes the Lead in Raising

European Union Funds:

Scientists at the Research Center

Awarded Nearly 20 Million Euros

Since 2002

The European Union Research Framework Programme is probably the largest support programme in the world for research projects. The main aim of the 6th Framework Programme (2002-2006) is to strengthen and structure European research more effi ciently. Scientists from the GSF-National Research Center for Environment and Health also actively participate in the 6th Framework Programme. Shortly before it ended, they show that they have been extraordinarily successful in raising European Union funds: So far the GSF has received € 19.5 million, distributed over 47 accepted proposals. Altogether 33 per cent of the proposals submitted by GSF scientists in the fi rst to third calls in the 6th Framework Programme (between 2002 and the end of 2005) were successful. The GSF is among the most successful applicants in German research and its acceptance rate is clearly above the average of about 18 per cent throughout the European Union-.

19 January

New Methods in the Fight Against

Leukaemia and Malignant Tumours

International experts in leukaemia treatment, cancer research, and immunology meet from 22 to 25 January 2006 at the 7th International Symposium on Immunotherapy organised by the University of Munich together with the GSF-National Research Center for Environment and Health, the German José Carreras Leukaemia Foundation, and the Aktion Kno-chenmarkspende Bayern (Action for Bone Marrow Donation Bavaria). The aim of the symposium is the exchange of new fi ndings among clinical physicians and research scientists from around the world in order to develop new approaches to the treatment of leukaemia and malignant diseases related to blood formation.

1 February

New Administrative Managing

Director at the GSF-National

Research Center for Environment

and Health

On 1 February the Administrative Managing Director of the GSF-National Research Center for Environment and Health, Dr. Hans Jahreiß, joins the headquarters of the European Southern Observatory (ESO) in Garching near Munich as Head of Administration.

Dr. Irmela Jeremias

Dr. Andrea Huber Brösamle

Prof. Hans-Jochem Kolb

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His successor as Administrative Managing Director of the GSF is the lawyer Dr. Nikolaus Blum, who headed the Personnel Department of the Center until mid-1997.

9 February

GSF Most Important European

Research Establishment in the

Field of Air Pollutants

The GSF-National Research Center for Environment and Health is number one among European research establishments in air pollutant research. This is the result of a ranking of the most widely cited publications on air pollution over the past ten years, published by ‚Essential Science Indicators‘.

20 March

Chernobyl – 20 Years On

On the 20th Anniversary of the Chernobyl reactor disaster some 20 science journalists from Stuttgarter Zeitung, Süddeutsche Zeitung, Zeit, Welt, TAZ und ZDF (German Tele-vision) join scientists from the Gesellschaft für Anlagen- und Reaktorsicherheit (GRS, Society for Plant and Reactor Safety) and the GSF in a study tour to look at the impact in Belarus and the Ukraine. The journey is organised and carried out by the GRS and the GSF.

Dr. Hans

Jahreiß

Dr. Nikolaus Blum

22 March

German Cancer Award 2006 for

Martin Göttlicher

Today Professor Martin Göttlicher, Director of the Institute of Toxicology of the GSF-National Research Center for Environment and Health, receives the German Cancer Award from the Deutsche Krebsgesellschaft (German Cancer Society) for „important contributions to the study of the development, diagnosis or treatment of cancer“.

29 March

From Roentgen to Chernobyl –

Benefi ts and Risks of Radiation

„Radiation – from Roentgen to Chernobyl“ is the title of the new issue of the GSF magazine „mensch+umwelt“. With this 64-page magazine, the GSF-National Research Center for Environment and Health reaches out to the interested public looking for infor-mation on fundamental questions about the effects and risks of ionising radiation.

13 June

Excellent Neuroresearch at the

GSF: Dr. Laure Bally-Cuif Is

Awarded Heinz Meier-Leibnitz

Prize

Bally-Cuif convinces the selection committee with her outstanding achievements in the neurosciences. At the Institute of Developmental Genetics of the GSF-National Research Center for Environment and Health, she investigates which mechanisms and factors regulate the development of nerve cells and the nervous system as well as the function of the brain of vertebrates, focusing on the midbrain and hindbrain region of Zebrafi sh. The Heinz Meier-Leibnitz Prize has

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6 July

The Benefi ts of Science: European

Union Commissioner Markos

Kyprianou Visits the GSF-National

Research Center for Environment

and Health

Recent results and new approaches to health research are the focus of the visit of EU Commissioner Markos Kyprianou today, Thursday, to the GSF-National Research Center for Environment and Health. At the Neuherberg research facility, the Commissioner for Health and Consumer Protection gathers information about topics relevant to his departmental brief. The evalua-tion of health costs, smoking and health, the networking of epidemio-logical projects and the prospects for inhalation therapy were at the centre of interest.

9 – 14 July

„nano“ Camp 2006: Experiencing

Science as an Adventure

Discover, investigate, experiment wildly: twelve young people have the chance to experience science as an adventure at the „nano“-Camp from 9 to 14 July 2006. In the Year of Computer Science the 3sat future magazine „nano“ and the Munich Research Center for Environment and Health (GSF) invites 16- to 18-year-olds to the fi fth „nano“-Camp. For one week they do not go to school, but learn a lot every day anyway. They also appear on television: „nano“ shows daily what they experienced and investigated.

11 July

„Pallas Athene“: Opening

Meeting with Minister of State

Christa Stewens

Minister of State Christa Stewens gives the go-ahead for the initiative „Women in Science – Science for Women“ at the GSF-National Research Center for Environment and Health. In presentations on various topics outstanding women

been awarded to young scientists in recognition of outstanding achieve-ments since 1977. The prize is worth € 16,000 and is intended to help the winners to pursue their scientifi c career.

23 June

Environment Prize for Bavarian

High School Graduates

On Tuesday 27 June 2006, the Undersecretary of since 1977 Dr. Otmar Bernhard awards the prizes in this year‘s „Carl Friedrich von Martius Environment Prize“ to ten Bavarian high school graduates in a celebration at the GSF Research Center, Neuherberg. There were a total of 101 entries in the competi-tion, out of which four girls and six boys were awarded prizes worth a total of € 7,500 for their school research papers. The participants had to work on environmental or health topics. The prize is awarded in commemoration of the Bavarian tropical researcher and physician Carl Friedrich Philipp von Martius (1794 – 1868).

Minister of State Christa Stewens

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scientists will describe individual projects to representatives from industry, science and politics. The event is intended to draw particular attention to the work of women scientists and to give them more support. It is part of a programme supported by the European Union with a total of € 220,000 under the category Science and Society in which the GSF-National Research Center for Environment and Health participates together with fi ve other centres from the Helmholtz Associa-tion.

8 September

HASSIP 06: Biomathematicians

from All Over the World Meet at

Neuherberg

The Institute of Biomathematics and Biometry of the GSF-National Research Center for Environment and Health holds an international workshop on ‚Multiscale Methods, Sparse Decompositions and Parsi-monious Statistics‘ from 11–14 September 2006. The workshop is designed as the fi nal event of the European Research and Training Network on Harmonic Analysis and Statistics for Signal and Image Processing (HASSIP), and deals with the linking ofmethods of harmonic analysis and statistical modelling for image and signal processing.

18 September

Effects of Fine Particles and Traffi c

Pollution on Health:

Two New Publications on Mortality and Respiratory Disease in 4800 Women from North Rhine-WestphaliaAn important paper on the impacts

21 September

100 Years of the Asse II

Research Mine

More than 400 visitors celebrated the 100th anniversary of the estab-lishment of the Asse mine. In his commemorative address the Director, Guenther Kappei, outlines the eventful history of the mine from the mining of potash and salt to the fi nal disposal of low- and medium-level radioactive waste and fi nally the preparation for closure.

7 September

International Initiative for the

Elucidation of the Function of All

Genes Started

The Conditional Mouse Muta -genesis Project EUCOMM, funded by the European community with € 13 million, and its Canadian partner project NorCOMM receive support from the USA: today, 7 September, is the start of the American National Institutes of Health Knockout Mouse Project (KOMP). The three large projects will work in close co-operation to mutate virtually all the genes of the mouse genome, so that mouse models can be used to elucidate the functions of all genes.

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of fi ne particles and traffi c pollution on mortality in Germany appears in the September issue of the scientifi c journal ‚Epidemiology‘. These new results support a recently published study on the occurrence of respira-tory disease.

22 September

Munich Children –

What Risks Are They Really

Exposed to? The GSF-National

Research Center and Münchener

Rück Stiftung (Munich Re Founda-

tion) Invite to a Discussion

The GSF-National Research Center for Environment and Health and the Münchener Rück Stiftung organise a panel discussion in Munich on Thursday evening on the topic ‚Munich children – what risks are they really exposed to?‘ Interested Munich residents and representa-tives of environmental and health authorities and from politics and the industry are invited. The evening is the fi rst of a series of discussion forums with which the two organi-sers – science and industry working together –pursue the common goal of raising the awareness of the Munich population of genuine risks.

9 October

New Gene Discovered for Heredi-

tary Form of Rickets

Scientists from the GSF-National Research Center for Environment and Health have identifi ed mutations causing a specifi c form of hereditary rickets due to phosphate defi ciency. As the research team of the human geneticist Dr. Tim Strom reports in the renowned scientifi c journal Nature Genetics, the mutations occur in a gene on chromosome 4 which is responsible for the pro-duction of dentin matrix protein.

Dr. Tim Strom

29 September

Invitation to the Panel Discussion

‚Soupy Air in the City – Do Fine

Particles Make the Residents of

Munich Sick?‘

On Thursday, 5 October the GSF-Research Center continues its series of panel discussions with the Münchener Rück Stiftung on ‚Risks for Munich Residents‘. The second evening is devoted to a topic that has recently moved to the forefront again following the recent European Union resolutions: ‚Soupy Air in the City – Do Fine Particles Make the Residents of Munich Sick?‘

2 October

Lysimeter Workshop at the GSF-

National Research Center for

Environment and Health

An international workshop on ‚Lysimeters for Global Change Research: Biological Processes and the Environmental Fate of Pollut-ants‘ is held from 4 – 6 October at the GSF-National Research Center for Environment and Health. Over the three days nationally and internationally renowned scientists discuss current developments in the fi eld.

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9 November

The Next Flu Wave is Bound to

Come – How Well is Munich

Prepared for an Epidemic?

The GSF continues its panel discus-sions with the Münchener Rück Stiftung on ‚Risks for Munich Residents‘. Experts and citizens discuss the topic ‚If and when it comes -- How well is Munich prepared for an epidemic?‘ at the Bavarian State Library. What are the health risks from infectious di-seases? Bird fl u and infl uenza – how dangerous are they? How well prepared are the city and the State of Bavaria for a pandemic? How are physicians and hospitals preparing for an emergency? Vaccination, reserve stocks of drugs, and more – what really helps?

20 November

Dialogue Between Art and Sci-

ence: Works by the Artist Dirk

Rathke at the GSF-National

Research Center

The GSF continues its series of dialogues between art and science with room designs and visual objects by the artist Dirk Rathke. The exhibition focuses on the

presentation of the concept of temporary locally-fi xed wall paint-ings. Rathke studied in Berlin at the Hochschule der Künste until 1997 and then as a master class student with Raimund Girke and Kuno Gonschior. He has created several room designs and visual objects in Germany and Switzerland.

21 November

Start of „School Goes to Re-

search“

Today the GSF and the Munich Bertolt-Brecht-Gymnasium (state grammar/high school) present their project for sustainable basic scientifi c education. To start with, the young researchers will collect scientifi c data on the relationship between temperature and sunlight up to the middle of February 2007 at their school. The project will run for fi ve years.

29 November

Great Responsibility for

Politicians and Journalists in

Dealing with Risks:

Invitation to a Discussion from the GSF-National Research Center for Environment and Health and Münchener Rück Stiftung The focus in the fi fth and last of the panel discussions in the series ‚Risks for Munich Residents‘ organised by the GSF-National Research Center for Environment and Health and the Münchener Rück Stiftung is not the risks as such, but how to deal with them. More than 120 representatives of local authorities, physicians, teachers and other interested Munich residents follow the invitation and join the discussion with high-ranking representatives from science, politics and the media.

6 December

Excellent Fine Particle Measure-

ment: Aerosol Measurement

Station is „Leitprojekt 2006 des

Kompetenzzentrums Umwelt“

(Lead Project 2006 of the Bavarian

Competence Centre for the

Environment)

The Augsburg aerosol monitoring station of the GSF-National Research Center for Environment and Health

Dirk Rathke

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14 December

Polonium-210:

No Dangerous Contamination

Found in Aircraft Passengers

After traces of polonium were found in three British Airways airplanes, the GSF-National Research Center for Environment and Health and the Forschungszentrum Karlsruhe offered to carry out polonium analyses of people where there were grounds for suspicion. Since then both centres have held a large number of discussions with those affected and in a few cases carried out polonium analyses. So far – as expected – no high levels of polonium contamination were found in any of the samples.

20 December

Future Forum Science at the GSF:

Ethics in Medicine and Biology

Yesterday renowned experts discussed the question ‚Ethics – a Question of Location?‘ at the GSF-National Research Center for Environment and Health as part of the Future Forum Science.

„The GSF addresses questions related to the broader society that arise as a result of our scientifi c research“, explains the Scientifi c Managing Director of the GSF, Professor Günther Wess. It is important to look further afi eld, far from science and any publications. Especially in research into the medicine of the future, a central focus of the GSF, the awareness of global connections, makes it possible to learn from other sciences and other countries.

and its project partners are awarded the title ‚Offi zielles Leitprojekt 2006 des Kompetenzzentrums Umwelt‘ (Offi cial Lead Project of the Bavarian Competence Centre for the Environ-ment) for its contribution to environ-mental and health protection. The GSF co-operation partners are the Wissenschaftszentrum Umwelt (WZU, Environment Science Centre) and the Chair of Solid-State Chemistry of the University of Augsburg, the University of Augs-burg, the Augsburg University of Applied Sciences (FH) and the Bavarian Institute of Applied Environmental Research and Technology (BIfA). At the GSF the Institutes of Epidemiology and Ecological Chemistry and the project fi eld Health Relevance of Aerosols are involved in the project.

7 December

GSF Scientist Is Awarded the

Gottfried Wilhelm Leibniz Prize

Award Highlights the Importance of Neuherberg Stem Cell ResearchToday the German Research Foundation (DFG) publishes the list of the winners of the Gottfried Wilhelm Leibniz Prize 2007, the most valuable German award for the promotion of science. One of the awards goes to the stem cell scientist Professor Magdalena Goetz from the GSF-National Research Center for Environment and Health and the Ludwig- Maximilians-University Munich.

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Structure and Development Plan

The GSF investigates the founda-tions on which the future of medicine and healthcare are based, as well as environmental systems. Here, our interdisciplinary research focuses on the environment‘s considerable infl uence on human health and its role in the emergence and development of many complex diseases that are and will continue to be among the main causes of mortality and morbidity in the world.

In the future, medicine will focus more and more on prevention. It will concentrate on personal risk factors and look for causal therapies. For this reason the GSF concentrates on interactions between individual genetic disposition, biological systems and environmental factors. Current research approaches are directed towards elucidating the molecular mechanisms of environ-mentally related illnesses, including allergies and lung diseases, the effects of radiation, fi ne dust and aerosols on homeostasis and the therapeutic sensitivity of tumours.

We investigate natural resources such as plants, water and soils using a holistic ecosystem approach. Future research on health and the environment will have to analyse fundamental processes of disease development, the damage to organisms and how they defend against and compensate for this. Such investigations involve many different indications and disciplines, and the GSF is in a position to conduct them successfully thanks to its extensive range of skills and

expertise, particularly in the areas of genome research, cell biology, bioinformatics, biomathematics, chemistry, physics, and medicine. The GSF brings together the fi elds of biomedicine and environmental research unlike any other organi-sation, both within the Helmholtz Association and worldwide. Using the close links that the GSF has with hospitals, it can analyse the molecular mechanisms of disease development and develop new individualised approaches in diagnostics, prevention, and causal therapy. We are continuing to develop this interdisciplinary and cross-indicational approach on the basis of the rapid advances being made in health and environmental research.

Structure and Development Plan of the GSF-National Research Center for Environment and Health

Strategic Approach

Ionising radiation made visible.

Natural radioactivity can be proven

using a mist chamber. Lines of

condensed water form along the

path of the particles.

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In the future we will pay particular attention to the areas of systems biology, chemical and structural biology, scientifi c data processing and modern image-processing techniques. For this, the GSF relies on excellent funda-mental research, internationally used experimental platforms, clinical co-operation groups and centres for translational medicine. The aim is to closely link research and clinical applications. As the national centre of competence, the GSF will also continue to carry out important tasks within the fi eld of radiation research and radiation protection.

The GSF has the following organisational and procedural principles: grouping of projects in thematic fi elds for better inter-disciplinary coordination; indepen-dent institutes and departments to ensure scientifi c excellence (directors usually appointed jointly with universities); technology platforms that are used mutually by all institutes and fi nancing through the Helmholtz Association pro-gramme-oriented funding and by grants. The individual projects can be grouped into four complementary thematic fi elds. �

Environmental Factors and Health The fi eld of “Environmental Factors and Health” investigates the mechanisms of chemical and physical environmental factors, as well as the defence and compen-satory mechanisms of the organism. The main challenges here lie in the analysis of agents harmful to human health, such as chemical and physical environmental componen-ts, and in identifying the genetic basis and development mechanisms of human diseases. The aim is to identify particularly relevant compo-nents of biological systems and to characterise individual susceptibility to environmental factors. This creates a knowledge base for the prevention, diagnosis and therapy of ailments. This thematic fi eld brings together internationally recognised institutes that work in the area of epidemiology using databases and platforms such as KORA, in radiation and aerosol research and in toxicology.

Biobanks will play an important role in the coming years, archiving samples from both epidemio-logically registered population collectives and from genetically defi ned models from mouse projects. Future research will focus on the role of environmental factors in the development of cancer and, in particular, on furthering our competence in researching the biological effects of ionising radiation in a Munich centre for radiation research.

We will also put an emphasis on inhalation research, using our existing expertise on the effects of air pollutants to build up a main research focus on infl ammatory and allergic lung diseases and the effects of pollutants on the cardio-vascular system. The GSF is also establishing an interdisciplinary pneumology centre as a Helmholtz translational centre with institutes of experimental and clinical pneu-mology. And we are also looking into aspects of health economics and public health research. �

Wonders of nature. Leafhoppers

produce brochosomes to protect

themselves against water

droplets. Brochosomes have been

found in fi ne-dust samples taken

from the air.

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The focus in the fi eld of “Mecha nistic Principles of Health and Disease” is on the molecular mechanisms of hereditary diseases, development and neurobiological questions and the role of stem cells. We characterise the function of the genomes of model organisms, for example mice and zebra fi sh, and extrapolate the results to analogous mechanisms in humans.

The major results expected in the next fi ve to ten years include the development of mouse models for human diseases, the detailed characterisation of these in the German Mouse Clinic and better accessibility to human genotypes. These advances will lead to a completely new information situation, which will require new instruments and structures both with regard to the experimental and genetic-epidemiological approach and for data analysis. The possi-bilities offered by chemical biology and the elucidation of functional modules will play a substantial role in this and lead us more and more into the realms of systems biology, which will contribute to the creation of mathematical models and simulations of disease processes.

The strength of the thematic fi eld lies in joining experimental and theoretical groups. From mono-genetic to complex diseases, which are particularly infl uenced by environmental factors, there are leading international research projects in many fi elds. These are not only pursued in the laboratory, but also in silico.

The GSF has initiated research consortia like the German Gene Trap Consortium and the ENU Muta- genesis Programme, which have achieved international prominence. The same applies to the bioinfor-matics annotation databases. As a central instrument, the German Mouse Clinic II for “genome-environment interactions” is to be extended both for the GSF and as an international platform. Here, specifi c changes will be made in the environmental conditions using genetically defi ned mouse models, so that their molecular effects can be investigated.

An intensive collaboration within the GSF, especially with the fi eld of Environmental Factors and Health, will take us to the next stage in the systematic research into genome-environment interactions. �

Infection and Immunity The focus in the fi eld of “Infection and Immunity” is on the develop-ment of new immune and gene therapeutic strategies for the treat-ment of malignant tumour diseases and chronic virus infections. This research is primarily concerned with tumour diseases of the haemato-poietic system.

We systematically characterise molecular mechanisms and genetic alterations that can be caused, for example, by viral infections or the reorganisation of existing genetic material. Using viral model systems, for example those based on the Epstein Barr virus and HIV, we investigate the interactions of viruses with their human target cells and the contribution of these viruses to the development of tumours and multifactorial diseases. The elucidation of principles of cell growth, virus replication, and signal transfer by cellular and viral receptors will contribute substan-tially to understanding of the

Foundations of the medicine of the

future. One of the greatest challenges

in AIDS research is developing a

vaccination that stimulates the

immune system to fi ght HIV (fi g.

scanning electron microscopic picture).

Scientists at the GSF Institute for

Molecular Virology achieved initial

successes with a serum based on a

genetically modifi ed vaccine virus.

Mechanistic Principles of Health and Disease

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Ecosystems and Health

One of the research focuses at the

GSF is on ecosystems that ensure the

sustenance of humans for the future.

The ecological consequences of growing

energy plants such as rape and maize

are investigated at the experimental

facility in Scheyern.

Clean water through research. The GSF

Institute for Ground-Water Ecology

looks into the reduction and transport

of contaminants in ground water and

their effects on ecosystems.

The outdoor lab. Lysimeters are

stainless steel cylinders with a porous

fl oor plate that contain soil from the

original location. The plants in lysi-

meters are used to investigate how

various environmental factors infl uence

growth or how herbicides are removed

from soil.

The thematic fi eld “Ecosystems and Health” looks at the complex interactions between abiotic and biotic components in environmental ecosystems and their infl uence on the quality of the most important components of human diet: plants and water. An important goal here is to reduce the use of chemicals in agriculture and to optimise the use of soil and water self-purifi cation potential by regulating microbial processes.

In microbial ecology, the description of microbial communities has reached a point at which compelling questions are being raised about the function and activity of organisms in their respective environments (particu-larly in soils and ground-water). Further, microbes do not exist isolated in their environment; rather they interact in a complex manner with other organisms such as protozoa, plants, and humans, which opens up completely new

areas of research. Thus in this thematic fi eld the emphasis will be on the interactions between micro-organisms and plants as well as microbial ecology.

The disciplines of plant patho-logy and microbial ecology established in these two areas are in the process of interlinking and starting to address new queries related to biological systems that go beyond their own thematic limits. We will continue to establish interdisciplinary foci on the inter-actions between micro-organisms and plants in the rhizosphere, and on the activation of plant immunity. In the long term, this thematic fi eld contributes to the prevention of environmental diseases through research into environmental processes that are a prerequisite for a healthy basis to life, for example drinking water, soils, and foodstuffs free of pollutants. �

development of these diseases and will deliver new hypotheses for therapeutic approaches.

A further important focus in this thematic fi eld is research into questions of how malignant cells avoid immune defence and affect immune regulation. Building on this, approaches for targeted modulation of the immune system for treating tumours can be developed on the basis of in vitro studies and animal models. The networking of the thematic fi eld with both Munich universities through clinical co-operation groups, in which biomedical basic research is effectively linked with clinical research, is exemplary here. The establishment of a GMP (good manufacturing practice) laboratory will strengthen the transfer of new strategies for the prevention, diagnosis, and therapy of infectious and malignant illnesses into clinical practice. This facility, unique in the Munich area, will help us clinically test cell-based therapeutic approaches. �

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Supporting Activities

national and international advisory commissions also guarantees that new research results are included in the development of new guidelines and legal measures. �

The creation of centres of excellence to promote top research requires interdisciplinary cooperation and a coordinated research strategy. They will further strengthen the existing co-operation with the Munich universities, other Helmholtz centres, and leading international institutions. The international experimental research platforms, such as the German Mouse Clinic, the Genome Analysis Centre and the environmental simulation facilities, and the technology transfer centres are an important tool in building these networks, and for closely linking research and application. Particular value is placed on the training and advance-ment of the next generation of scientists and on personnel develop-ment. We have implemented a number of measures to ensure equality of opportunity. Cooperation with industry will be developed further using new business models. We also aim to further the exploitation of new technologies and application of results in practice, for example by establishing spin-off companies. The work of GSF scientists in

Translational research up close.

This brochure, published in 2006,

informs about how the GSF Research

Centre for Environment and Health

uses its fi ndings in clinical applications

and how it incorporates the expertise

from the clinic into its biomedical

research work.

There are GSF scientists in many committees

and commissions, such as the International

Commission on Radiation Protection (ICRP) and

the United Nations Scientifi c Committee on the

Effects of Atomic Radiation (UNSCEAR).

� 18

CCG

Clinical Cooperation Groups

The clinical cooperation groups are established as time-limited projects based on excellent existing scientifi c collaborations and are integrated in the research themes of the GSF.

Antigen-specific Immunotherapy

Environmental Dermatology and Allergology

Haematopoietic Cell Transplants

Immunoregulation in Childhood

Immunotherapy of Urological Tumours

Innate Immunity

Inflammatory Diseases of the Lung

Molecular Neurogenetics

Molecular Oncology

Osteosarcoma

Paediatric Tumour Immunology

Pathogenesis of Acute Myeloid Leukaemia

Tumour Therapy with Hyperthermia

Allergy trigger.

A picture of

birch pollen taken

through an

electron micro-

scope.

Putting the heat on tumours.

The SIGMA_EYE_MR Applicator

combines hyperthermia and nuclear

magnetic resonance (NMR).

Prof. Dr. Rolf D. Issels presented

the results of the world‘s fi rst ever

randomised phase-III study in

June 2007. They prove the effi cacy

and superiority of combined

treatment method (hyperthermia

plus chemotherapy) to chemo-

therapy alone.

The following cooperation groups have been established together with Ludwig Maximilians University, the Technical University, the Max-Planck Institute of Psychiatry (all in Munich) and the Asklepios Specialist Clinics in Munich-Gauting:

19 �

PTT and Ascenion

CC

G –

PT

T –

Asc

enio

n

Within the GSF, PTT represents the central interface between scientifi c research and industry. PTT gives legal advice and support to GSF

Patents and Technology Transfer (PTT)

Ascenion is an agency for intellec-tual property asset management focused on the life sciences. In co-operation with the PTT, Ascenion helps GSF scientists evaluate the market potential of their research results and develop and execute optimal marketing strategies such as licensing, cooperation, sale or founding a new company. Ascenion holds equity in several spin-offs and can thus benefi t from the corporate growth and future success of these

Ascenion GmbH

ventures. Revenues from licence agreements or the sale of equity are channelled back to the inventors and research institutions.

Ascenion is a 100% subsidiary of the Life-Science Foundation for the Promotion of Science and Research and the exclusive commercialisation partner of 12 life-science institutes in the Helmholtz and Leibniz Associations and of Hanover Medical School.

Successful knowledge transfer from

research to practice. The spin-off

company Isodetect GmbH was founded

at the GSF and the Helmholtz Centre

for Environmental Research in collabo-

ration with Ascenion GmbH. Isodetect

investigates stable isotopes in residual

contaminations and proves the natural

reduction of harmful substances in

polluted areas. Using bacteria traps

(BACTRAP®; Foto) the isotopic

composition of microbial biomass is

investigated at a location due for

rehabilitation. The absorption of the

isotopic market into the bacterial

biomass shows that the bacteria have

degraded the pollutant and that a

biological self-cleansing process is

taking place.

scientists on all patent matters including invention disclosure, patent applications and their coordination with inventors and

patent attorneys. Outside the GSF, PTT collaborates closely with Ascenion GmbH with the aim of initiating industry co-operations and maintaining contacts with existing and/or potential licensees. PTT currently manages around 115 patent families in Germany and abroad.

� 20

Thematic Field: Environmental Factors and Health

ue to the additive interaction of several susceptibility loci a hereditary predisposition for

radiation-induced bone tumours (osteosarcomas) may develop in mice. In man, this type of tumour is becoming increasingly important as a secondary tumour following child -hood radiation therapy. Our search for inherited susceptibility factors in mice shows, that the accidental co-segregation of high-risk alleles from both parental animals results in a signifi cant increase in the individual bone tumour risk in some of their progeny.

A hereditary infl uence on the risk of bone tumour development following radiation exposure has only been known for a few rare hereditary diseases which lead to a high frequency of a number of tumours in some families. Due to their severe effects, which often affect very young patients, however,

the mutations underlying these so-called familial cancer syndromes are rarely found in the population.

In genetic tests of radiation-induced bone tumours in various mouse strains we could identify chromosome sections which had been unknown, and which only increase the frequency of this type of cancer, when they are combined. In these instances an accidental combination of risk alleles from both parents may result in a heredit-ary predisposition for these bone tumours, which had not been seen in previous generations.

Translating our fi ndings to the situation in the human population one might expect to fi nd hyper-sensitive person which, in contrast

Hereditary Factors Modify Risk of Bone Tumour Following Radiation ExposureInstitute of Pathology

Dr. Michael Rosemann

Institute of Pathology

Telephone +49 - 89 / 31 87-26 28

[email protected]

D

Cumulative osteosarcoma incidence

following injection with the bone-

seeking alpha-emitter thorium227

shows that a combination of suscepti-

bility loci from the parental BALB/c and

CBA/CA strains (dotted lines) may occur

in the F2 generation (solid lines), which

results in a hypersensitive (5 x S) or

hyperresistant (5 x R) phenotype in the

offspring.

0

0.2

0.4

0.6

0.8

1

0 200 400 600 800

Latency period/days

Tu

mo

ur

incid

en

ce

5 x S

CBA

BALB

5 x R

to the case of familial cancer syndromes mentioned, are not characterized by the existence of close relatives with early or frequent tumor incidences. Therefore, the examination of a family history may not be very promising. More characteristic indications of a hereditary predisposition, however, would be: Unusually young age of tumour development or patients with multiple tumours.

This work brought us a good deal closer to the aim of determi-ning such a hereditary predispositi-on by a molecular test, before any clinical symptoms are manifested.

Literature:

� Rosemann, M., Kuosaite, V., Kremer, M., Favor, J., Quintanilla-Martinez, L., Atkinson, M.J.: Multilocus inheritance determines predisposition to alpha-radiation induced bone tumour-igenesis in mice. Int. J. Cancer 118, 2132-2138, 2006.

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illions of people – suffer-ing from colds and a runny nose – self-medi-

cate with a diversity of nose sprays known from advertisements. One of these preparations (Nasivin) contains oxymetazoline as active ingredient. The patients are using the well-known property of oxy-metazoline to reduce swelling of mucous membranes. In addition, a signifi cant antiviral and anti-infl ammatory effect has been observed in in-vitro studies.

In a study supported by Merck Selbstmedikation GmbH, Darm-stadt, a research group from the GSF-Institute for Inhalation Biology found that oxymetazoline inhibits the release of infl ammatory promoting signal substances in alveolar macrophages, the phago-cytic cells of the immune system, and at the same time promotes synthesis of anti-infl ammatory signal molecules. Oxymetazoline was also able to markedly reduce the oxidative burst elicited experi-

mentally in the cells by the treat-ment with ultrafi ne carbon particles. The oxidative burst is the result of reactions to produce highly reactive oxygen radicals in the cell for chemical detoxifi cation; but it also represents an immense oxidative stress for the cell.

These new studies are very interesting because they show that oxymetazoline possesses not only decongestant properties but in addition is able to inhibit the infl ammatory response and the oxidative stress occurring during a cold. Studies will continue in order to increase our understanding of these fi ndings.

Literature:

� Beck-Speier, I. et al.: J. Pharmacol. Exp. Therap. 31, 843-851 (2006)

Additional Mechanism of Action Found for Oxymetazoline

Institute of Inhalation Biology

Dr. Ingrid Beck-Speier


Telephone +49 - 89 / 31 87-25 52

[email protected]

M

Electronmicroscopic

image of an alveolar

macrophage, taken up

agglomerates of

ultrafi ne carbon

particles within 1 h in

its phagolysosomes.

800 nm

� 22


igh resolution computed tomography is a very promising technology for

non-invasive examination of the coronary arteries (angiography). Scientists at the „Deutsches Herz-zentrum“ working with colleagues from the GSF-Institute of Radiation Protection have shown that by using appropriate examination protocols, the radiation exposure can be reduced by up to 64% compared with the standard protocol.

Multislice computed tomography is a non-invasive technology suitable to accurately identify coronary artery narrowings and calcifi ed and non-calcifi ed plaque at high resolution. However, at present CT investigations tend to be asso-ciated with a relatively high radia-tion exposure for the patient. High-resolution CT imaging is used increasingly as the diagnostic technology of choice because of its high information content, thus it is important to try and reduce the associated radiation exposure.

A retrospective analysis of the radiation dose for 1035 patients undergoing coronary CT angiogra-phy (CTA) with 16 or 64 slice CT, performed by the scientists showed that by using optimised scan protocols like ECG-dependent dose modulation in combination with reduced tube voltage, it was possible to reduce the radiation dose by as much as 64%. The results show that – despite the increased radiation dose for coronary CTA that is in

principle associated with the increase in spatial and temporal resolution of 64-slice CTA – opti-mised and dose-saving examination protocols can contribute to a substantial reduction in the medical radiation exposure of the popu-lation.

Literature:

� Hausleiter, J. et al.: Circulation 113, 1305-1310 (2006)

Reduction of Radiation Exposure in CT Angiography

Institute of Radiation Protection

Maria Zankl


Telephone +49 - 89 / 31 87-27 92

[email protected]

H

Multi-slice CT angiography (CTA)

Promising technology for imaging patients with

suspected coronary artery disease

– However: patient dose generally high with CT– Compared to 16-slice CT, 64-slice CT results in

an increase of spatial and temporal resolution as well as patient dose

Retrospective study of

– patient doses of 16- and 64-slice CTA in clinical practice (1035 patients)

– infl uence of different examination protocols on patient dose and diagnostic image quality (260 patients)

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ultiple endocrine neoplasia (MEN) is a generic term for a rare, inherited disease, in

which tumours can arise in internal hormone producing (endocrine) organs. Organs that can be affected by tumours include the thyroid gland, pituitary gland, pancreas, and adrenal gland. So far mutations have been identifi ed in two different genes which cause predisposition to tumour development and that are inherited as autosomal dominant traits. This means that statistically the disease will be passed on to every second child if one parent is a carrier. Once it is known that the gene mutation is present in a family, tumours can be identifi ed at an early stage through early and regular investigation and treatment is more effective. However, many MEN patients don‘t display mutations in either of the known genes. Scien-tists from the Institute of Pathology working together with colleagues from the University of Goettingen have identifi ed a further gene – Cdkn1b – in a rat model of MEN that can lead to the development of multiple endocrine tumors also in humans. The gene codes for a protein (p27kip1) that has a regula-tory function in the cell cycle and can thus affect cell division. Thus genetic counselling of affected families can now use a third gene to further support prevention of MEN. Furthermore, the rat model offers a

promising experimental system in which the development of endocrine tumours can be investigated further and potential targets for new therapy identifi ed.

Literature:

� Pellegata, N. S. et al.: Proc. Natl. Acad. Sci. USA 103, 15 558-15 563 (2006)

Identifi cation of a New Mutation Enhances the Prevention of Inherited TumoursInstitute of Pathology

Dr. Natalia Pellegata


Telephone +49 - 89 / 31 87-26 33

[email protected]

M

Biological material

Novel tumor markers for the diagnosis and prognosis of human NE tumors

NE tumors

DNA RNA Proteins

Rat modelA translational

research approach to

study neuroendocrine

(NE) tumors.

� 24


study published by GSF epidemiologists together with Dutch colleagues

identifi es for the fi rst time an association between the occurrence of middle ear infection or infl amma-tion (otitis media) in children and traffi c related air pollutants.

It has been known for a long time, that environmental factors such as exposure to environmental tobacco smoke play a role in the development of middle ear infec-tions in infants and young children. In two prospective studies, data from 4150 Dutch children and 670 Munich children were collected from the time of pregnancy onwards starting in 1997-1999. The individual burden of traffi c-related ambient air pollutants resulting from each child‘s local environment was modelled on the basis of spatial

measurements of ambient air pollutants, including fi ne particles and nitrogen dioxide, and data of the Geographic Information System (GIS) such as distance to major roads, traffi c volume and population density. Information about the occurrence of middle ear infections in the fi rst two years of life was collected by questioning parents. Possible risk factors like socio-economic status of the parents, parental allergies, and exposure to environmental tobacco smoke were taken into account. Both the Dutch and the German study group showed a clear correlation between the occurrence of disease and the exposure to the traffi c-related air pollutants: fi ne particles and nitro-gen dioxide. The scientists suspect that the same mechanisms of action are responsible for the association

between air pollutants and otitis media as are assumed for passive smoking and otitis media.

In view of the fact that traffi c-related air pollutants are a constant source of exposure, and that middle ear infections are among the most common acute infections in infants and have a variety of late effects on health, these results have far-reaching implications for the risk assessment of exposure to fi ne particles.

Literature:

� Brauer, M. et al.: Environ. Health Persp. 114, 1414-1418 (2006)

Air Pollutants as a Cause of Middle Ear Infections

Institute of Epidemiology

Dr. Joachim Heinrich


[email protected]

A

Life time prevalence: 75% in children

below 3 years; most common infections

in childhood and a common reason for a

doctor consultation; main reason for

antibiotic course in early childhood;

increasing trend of incidence

Complications: Hearing loss, language

development, and life quality are limited.

Risk factors: Exposure to environmental

tobacco smoke, ambient air pollutants as

risk factors are rarely investigated yet.

Bacterial (60%) or viral (40%) infections of

the middle ear, infl ammatory swalling of

the mucosa, infection route via nose and

throat area.

acoustic meatus

eardrum

ossicle

tympanum

cochlea

nose and throat area

eustachiantube

internal ear

middle ear

external ear

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t is currently estimated that 40 to 70 per cent of all cases of obesity are linked with an underlying

genetic component. Meanwhile many chromosomal loci and genes are known, whose activation or elimination is linked with the development of obesity (adiposity). However, only a fraction of these genes can cause overweight by themselves, it is the combination of various genetic factors as well as a lifestyle with a high-energy diet and lack of exercise which makes us put on too much weight. Among other things adiposity is associated with an elevated risk of high blood pressure, type 2 diabetes, heart attack and some cancers. A genetic variant has now been identifi ed, which is found in approx. 10 per cent of the population and which increases the risk of overweight and adiposity in children and adults.

An analysis of a total of about 100,000 gene variants in the human genotype from samples of the Framingham Study carried out by a group of scientists from Boston University (Prof. Christman) looked

specifi cally for characteristics which are found more frequently among overweight people. A change in the genotype was discovered near a gene which controls the fat metabo-lism. The gene variant classifi ed as rs7566605 is on chromosome 2 in the immediate vicinity of the “insulin-induced gene2” (INSIG2) and is found in people of both Western European and Afro-Ameri-can descent. The protein product of the INSIG 2 gene slows down the synthesis of fatty acids and choleste-rol. The changed activity of this gene could result in more fat being deposited in the tissue. In a repre-sentative sample of approx. 4000 people from the Augsburg Region (KORA) scientists from the GSF Institutes of Epidemiology and Human Genetics could show that people who carry this gene variant are signifi cantly heavier (measured by body mass index) than those who do not carry it. In parallel a team from the University of Duisburg-Essen studied this gene variant in almost 400 severely overweight children and their parents. It could be shown that the risk variant is

signifi cantly more often passed on by parents to their overweight children.

This insight can contribute to the elucidation of the molecular pro-cesses leading to overweight, which, in turn, is a prerequisite for the development of effective medication to help patients suffering from adiposity.

New Risk Factor for Obesity Discovered

Institutes of Epidemiology and Human Genetics, Genome Analysis Centre

I

C/C INSIG2 G/G Balance of sequence

variants in the INSIG2

gene:

In a comparison of large groups of people (n > 1000) sequence variant C in the INSIG2 gene is associated with signifi cantly higher weight than sequence variant G.

Prof. Dr. Thomas Meitinger (left)

Institute of Human Genetics

Telephone +49 - 89 / 31 87-32 16

[email protected]

Prof. Dr. Dr. Heinz-Erich Wichmann


Telephone +49 - 89 / 31 87-40 66

[email protected]

Literature:

� Herbert, A., Gerry, N.P., McQueen, M.B., Heid, I.M., Pfeufer, A., Illig, T., Wichmann, H.-E., Meitinger, T., Hunter, D., Hu, F.B., Colditz, G., Hinney, A., Hebebrand, J., Koberwitz, K., Zhu, X., Cooper, R., Ardlie, K., Lyon, H., Hirschhorn, J.N., Laird, N.M., Lenburg, M.E., Lange, C., Christman, M.F.: A common genetic variant 10 kb upstream of INSIG2 is associated with adult and childhood obesity. Science 312, 279-283, 2006.

� 26


he enzyme IKKβ acts as both an activator and an inhibitor of the initiation of immune

responses. This surprising discovery was reported by a group from the Institute of Toxicology working together with the Institute of Molecular Immunology of the Technical University, Munich, and the Harvard Medical School in Boston. The CBM complex is a high molecular protein complex which plays a central role in the triggering

of defence reactions, for example in response to pathogenic agents. Formation of this complex lies at the start of the signal cascade that leads to proliferation of defence cells and release of messenger molecules by the immune system. The IKKβ protein plays an essential role in the formation of the CBM complex, but over time it also causes a chemical change in one component. Thereby IKKβ induces the decay of the complex and thus an attenuation of signal propagation. The scientists suspect that the dual function of IKKβ may contribute to balance lymphocyte activation both by boosting and by slowing down immune reactions.

The newly discovered mecha-nism of action of IKKβ could offer a target for the treatment of diseases in which the immune activation is accelerated, for example in autoim-mune diseases or distinct lympho-

mas. By activating or enhancing the decay of the CBM complex, it may be possible to prevent overreaction of the immune system, as in auto-immune diseases, or proliferation of cancer cells, as in lymphomas. In a future project it is aimed to specifi cally interfere with the protein-protein interactions that are involved in the signaling process.

Literature:

� Wegener, E. et al.: Mol. Cell 23, 13-23 (2006)

New Insights Into a Signal Pathway of the Immune Response

Institute of Toxicology

Dr. Daniel Krappmann


Telephone +49 - 89 / 31 87-34 61

[email protected]

T

Association of Bcl10 with fi laments.

Bcl10 proteins are integral components

of the CBM complex. Green-fl uorescent

Bcl10 proteins bind to fi lament-like

structures outside the nucleus (blue).

The analysis of the functions of Bcl10

represents a central focus of the reserch

team headed by Dr. Daniel Krappmann.

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Thematic Field: Mechanistic Principles of Health and Disease

T echnologies for high-through-put mutagenesis are a prerequisite for the develop-

ment of large numbers of animal models of human diseases. Current mouse models of human diseases are mostly based on mutations of the respective genes. Analyzing these mouse models makes it possible to elucidate the biological functions of different genes, in particular, their involvement in the development of human diseases. This also provides a starting point for the discovery of novel therapies.

For example, the mouse models of Parkinson‘s disease are used to investigate the causes of the disease and the role of environmental factors on the severity of the symptoms.

Gene trapping is a leading technology for high-throughput mutagenesis. It involves using a gene trap vector to create insertio-nal mutations that are distributed randomly over the genome. As a mutagen, gene trap vectors inacti-vate a trapped gene while simul-taneously reporting its expression. The inserted gene trap vector also provides a unique signal for the identifi cation of the trapped gene. The cell lines generated by this

GSF Owns One of the Largest Libraries of Mutant Mouse Embryonic Stem Cells WorldwideInstitute of Developmental Genetics

Prof. Dr. Wolfgang Wurst

Director of the Institute of

Developmental Genetics

Telephone +49 - 89 / 31 87-41 10

[email protected]

technology can then be used to create transgenic mice as animal models for particular human diseases. This resource will provide researchers invaluable tools to study human diseases.

GSF Institute of Developmental Genetics has so far generated one of the largest academic libraries of mutant mouse embryonic stem cells worldwide. The library contains more than 67,000 molecularly characterized mutant embryonic stem cell lines that represent more than 6,300 different genes of the mouse. 417 of these genes are associated with human diseases such as Alzheimer‘s Disease, Parkinson‘s Disease, colon and breast cancer, Chorea Huntington, and nephritic syndrome. These cell lines are freely available for the academic community and can be requested from the International or the German gene trap consortia.

Literature:

� Hansen, J. et al.: Proc Natl Acad Sci USA 100: 9918-22 (2003)

Team leader Dr. Roland Friedel

is inserting a cell culture plate with

mutant embryonic stem cells into an

automated colony picker.

� 28


tem cells are multipotent and form different progenitor cells in the developing embryo or

in the adult organism. Stem cells also have the characteristic ability of self renewal. If this ability is missing, the number of stem cells decreases continuously during development and no stem cells can then persist into adulthood. Until now the factors that regulate the self renewal of neural stem cells in the developing brain were unknown. Now scientists from the GSF-Institute of Stem Cell Research have shown that the GTPase cdc42 is the key molecule for the self renewal of neural stem cells. GTPases are small molecular switches that activate other proteins when they are bound to the energy carrier guanosine triphosphate (GTP). If GTP is

converted into the low energy form guanosine diphosphate (GDP), the proteins are no longer activated.

The scientists were able to show that cdc42 regulates the self renewal of stem cells in the developing forebrain. Interestingly, cdc42 is enriched at one pole of the neural stem cells and hence is likely to be asymmetrically distributed when the stem cells divide. In this case one daughter cell remains a neural stem cell, while the second develops into a neural progenitor cell from which neurons are generated. If cdc42 is genetically deleted in these cells, the stem cells lose the ability to divide asymmetrically and thus to renew themselves. Instead only neural progenitor cells are formed, which eventually leads to a reduction in the number of neural stem cells.

This research provides a new stimulus for stem cell research: Aging of stem cells is linked to the fact that they gradually loose the ability to self-renew. The exciting fi ndings of cdc42-regulated self-renewal of neural stem cells prompt the hope that stimulation via cdc42 may help to activate self renewal in aging neural stem cells.

Literature:

� Capello, S. et al.: Nature Neuroscience 9, 1099-1107 (2006)

Switch for Self-renewal of Neural Stem Cells Discovered

Institute of Stem Cell Research

Prof. Dr. Magdalena Götz,

Director of Institute of

Stem Cell Research

Telephone +49 - 89 / 31 87-37 50

[email protected]

S

Section through the

forebrain of a 14-day

mouse embryo.

Cells in the M phase

of cell division in red

(PH3+).

Cover of the above

publication.

Cdc42

PH3

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ickets is a metabolic disturb-ance in children that is caused by vitamin D or phosphate

defi ciency. As a result of nowadays vitamin D prophylaxis, most of the rickets cases observed are caused by phosphate defi ciency. Scientists from the GSF Institute of Human Genetics have now identifi ed mutations in 2 genes, that cause specifi c forms of hereditary rickets which result from phosphate defi ciency.

The mutations occur in a gene on chromsome 4 (DMP1) which is responsible for the production of dentin matrix protein, which is mainly found in the mineralised bone matrix (1). Mutations of this

gene lead to phosphate defi ciency, hypophosphatemia. In this meta-bolic disease excretion of phosphate via the kidney is increased and phosphate is thus no longer avail-able for bone development. The results so far show, however, that mutations in other genes can also lead to this disease. Mutations in another gene that is responsible for the formation of a renal phosphate transport protein have already been identifi ed and thus contributes to the regulation of phosphate home-ostasis (SLC34A3) (2). Interest focuses on a protein that apparently plays a central role in the regulation of phosphate homeostasis since its serum levels are altered in individu-als with the relevant gene mutation.

The results indicate that the identifi ed genes are part of a yet unknown metabolic pathway which is essential for the balance in phosphate metabolism. This metabolic pathway could be the key to develop new approaches for the therapy of this disease. Further inverstigations of the scientists are focused on the elucidation of these molecular events.

Literature:

� Lorenz-Depiereux, B. et al.: Nature Genetics 38, 1248-1250 (2006)

� Lorenz-Depiereux, B. et al.: American Journal of Human Genetics 78, 193-201 (2006)

New Genes Discovered for Hereditary Forms of Rickets


Dr. Bettina Lorenz-Depiereux


Telephone +49 - 89 / 31 87-42 13

[email protected]

R

Typical signs of rickets:

The X-ray of an 18 months

old child shows bowing of

the long bones of the lower

extremities and widening

of the metaphysis.

� 30


iological structures often occur at different frequencies.Some structures are more

widespread than others. Why are some structures more successful than others? We investigate this question with respect to protein domains.

Based on the designability

hypothesis, robustness against mutation is a deciding factor of success of the structure. Mutations affecting proteins may involve substitutions, deletions, insertions and even duplications of sequences encoding and regulating the protein. Protein domains sharing overall structural similarity are termed „folds“. We estimate the designabi-lity of a particular fold by the number of families known to form that fold.

In accordance with our hypothe-sis, we found that folds predicted to be more designable are on average not only more widespread in human, mouse and yeast but have proliferated at a greater rate since the time of the common ancestor of these organisms.

Current research also suggests that most, if not all, known heredita-ry disease causing mutations in coding regions affect protein structure. Because more designable structures are expected to be more robust against mutations, we investigated whether hereditary disease-related proteins were predicted to be less designable.

We fi nd that relatively large numbers of proteins annotated with OMIM (Online Mendelian Inhe-

ritance in Man) associated diseases have folds with low numbers of families. In particular, protein structures of a lesser predicted designability were found to be associated with very frequent diseases.

Our results suggest that designa-bility is an important determinant of the distribution of structures in nature and their relation to human disease.

Literature:

� Wong P., Frishman D.: Designability, Distribution, and Disease. PLoS Comput. Biol. 2, e40, 2006.

Protein Designability and Disease

Institute of Bioinformatics

Philip Wong


Telephone +49 - 89 / 31 87-35 77

[email protected]

B

Example of a protein

with the highly ordered

c.37 fold (P-loop with

nucleoside hydrolase)

with 22 known families.

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arkinson’s Disease (PD) is the second most common neurodegenerative disease in

elderly people. Treatment of PD is diffi cult and purely symptomatic. In light of the demographic develop-ment of our society, fi nding new and effective therapies for PD has become also of considerable economic relevance. One approach, for example, is the development of cell replacement therapies. To this end, the molecular cues underlying

the development of neuronal populations have to be unravelled. The hallmark of PD is the degenera-tion of neurons producing dopa-mine, a key neurotransmitter of the brain. Scientists at the GSF Institute of Developmental Genetics have now shown that the secreted glycoprotein Wnt1 is a key molecule for the development of precisely these neurons in the midbrain.

Wnt1 regulates a genetic net-work including two transcription

Discovery of a Key Molecule for the Development of Dopaminergic Neurons Institute of Developmental Genetics

Dr. Nilima Prakash

Institute of Developmental

Genetics

Telephone +49 - 89 / 31 87-22 75

[email protected]

factors, which is essential for the establishment of the corresponding progenitor domain during embryo-nic development. Furthermore, Wnt1 appears to control the termi-nal differentiation of dopaminergic neurons in the midbrain at later stages of embryogenesis. These results suggest the signal trans-duction pathway controlled by Wnt1 to be a very promising target for novel therapeutic approaches in the treatment of PD. One approach would be, for example, the design of therapeutic ‚small molecules’ that can activate the Wnt1 signal transduction pathway in the adult brain and thereby promote the differentiation of neural stem cells into dopaminergic neurons.

Literature:

� Prakash, N. et al.: Development 133, 1:89-98 (2006)

P

By contrast to

wild-type (wt) mice,

Wnt1-/- (knock-out)

mice lack the gene

for Wnt1. Hence

dopamine-synthesiz-

ing cells (green) do

not differentiate

correctly in these

mice, i.e. they do not

produce a crucial

factor (Pitx3, red)

required for their

survival.

Wnt1 controls the

establishment of the

midbrain dopamin-

ergic progenitor

domain during early

embryonic develop-

ment (A) and their

differentiation

into dopaminergic

neu rons at later

stages (B).

A B

E9.5-10.5 E12.5

Nkx2-2

Otx2

Wnt1Shh

Wnt1

Pitx3

mDA neuronsmDA progenitor domain

� 32


n 2005 367,361 people died of cardiovascular diseases in Germany (1). In approx. 95 % of

these cases the cause of death was a macroscopic heart disease, e.g. a heart attack. These diseases are very responsive to treatment, so that a fatal outcome can often be prevented or delayed by years. In the remaining 5 % of all cases diagnosis, therapy and prevention are more diffi cult. In those cases sudden cardiac death occurs – often without any preliminary warning – i.e. a directly life-threaten ing arrhythmia of the cardiac cham-bers. Although it tends to occur more frequently in young people and high-performing athletes, neither the blood analysis nor the ECG nor the heart ultrasound imaging allows any reliable risk forecasts.

Over the last decade several genetic arrhythmias have been elucidated with the help of family

surveys. This intensifi ed the search for genetic factors for sudden cardiac death. It is diffi cult to examine large postmortal patient groups, but one parameter of the electrocardiogram (ECG), the QT interval, shows a clear association with sudden cardiac death.

Therefore, we investigated the genetics of the QT interval in the normal population. For this purpose the two KORA surveys F3 and S4 with a total of 6,500 parti cipants as well as another 1,800 subjects from the Framing-ham Heart Study in the US were examined. We discovered a clear association with gene variants in the promoter of the NOS1AP gene, which codes for the nNOS activa-tor protein (2). A frequent gene variant extends the QT interval by 3.5 ms (heterozygous genes) in 50 % of the population and by 7 ms (homozygous genes) in 10 % of the population. This makes it

the strongest known genetic factor for an ECG change.

Some fi rst studies of a cohort of people who died of sudden cardiac death also showed an association in this respect. The risk of heterozygous carriers of the gene variant was 30 per cent higher than that of other people and that of homozygous carriers was nearly twice that of other people. We are currently conduct-ing functional tests to elucidate the molecular mechanisms under-lying this association.

Identifi cation of a New Causal Gene for Cardiac Arrhythmias


Dr. med. Arne Pfeufer


Telephone +49 - 89 / 31 87-35 45

[email protected]

I

Level of signifi cance for sequence variants infl uencing the QT interval:

Each dot stands for one of 100,000 sequence variants in the human genome (x-axis from chromosome 1 to the X chromosome). The corresponding P-values are plotted on the y-axis. The dot marked with a circle corresponds to the signal in the NOSAP1 gene on chomosome 1.

Literature:

� (1) www.destatis.de

� (2) Arking, D.E., Pfeufer, A., Post, W., Kao, W.H.L., Newton-Cheh, C., Ikeda, M., West, K., Kashuk, C., Akyol, M., Perz, S., Jalilzadeh, S., Illig, T., Gieger, C., Guo, C.Y., Larson, M.G., Wichmann, H.E., Marbán, E., O‘Donnell, C.J., Hirschhorn, J.N., Kääb, S., Spooner, P.M., Meitinger, M., Chakravarti, A.: A common genetic variant in the NOS regulator NOS1AP modulates cardiac repolarization, Nature Genetics, 2006; 38:644-651.

6

5

4

3

2

1

0

Chr. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 1819 202122 X

-lo

g (

P-v

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W hat’s wrong with our genes when we face disease? An international

research consortium wants to answer this question. In the next three to fi ve years scientists will alter virtually all genes of the mouse genome to enable, via generation of mouse models, the functional analysis of human disease-related genes. The mouse genome is 99% identical to the human genome, rendering the mouse an ideal model organism. The mutation of mouse genes allows scientists to gain insight into the mechanisms of genetically determined diseases like Morbus Parkinson, cancer, and cardiovascular diseases.

The international research consortium will use both directed and random approaches to mutate all the mouse genes. The directed mutagenesis strategy, conditional gene targeting, is used to delete genes via homologous recombinati-on, that is, by exchange of DNA sequences. The random approach for gene inactivation, conditional gene trapping, includes the applica-tion of a so-called reporter gene whose expression can easily be detected in the mutant organism. The loss of function of the mutated genes allows characterizing their role in the healthy organism. Three research projects, all using targeted mouse gene inactivation strategies, are planning to closely collaborate

in an international effort: the European EUCOMM project and its Canadian partner project NorCOMM were joined in September by another research team, the KOMP project of the American National Institutes of Health (NIH). EUCOMM is funded by the European Commu-nity with € 13 million and is coordi-nated by Professor Wolfgang Wurst, Director of the GSF Institute of Developmental Genetics.

Prior to the establishment of the international research consortium, scientists had to confront a quite unsystematic, fragmented research situation. Some 6,000 of the appro-ximately 25,000 mouse genes were considered to be mutated and available. However, for a large proportion of these genes double or multiple naming had occurred. Furthermore, only 500 of these genes were conditionally mutated, i.e. alterable in a time- and space-controlled manner. In addition, the cost of developing individual mouse models was quite high. “A commit-tee of the international consortium will now coordinate its joint activities and control completeness and effi ciency of the mutagenesis effort”, says EUCOMM Project Manager Dr. Cornelia Kaloff, GSF-Institute of Developmental Genetics.

A large proportion of the required technology was developed by Professor Wurst and his colleagues in conjunction with the International Gene Trap Consortium and the Wellcome Trust Sanger Institute, Hinxton, UK. Very soon, the inter-national scientifi c community will be able to, via a central database,

obtain mouse embryonic stem cells with single mutated genes rapidly and at a reasonable price to create mouse models for any desired genetically determined disease.

Literature:

� J. Auwerx et al.: The European dimension for the mouse genome mutagenesis program. Nat. Genet. 36 (2004) 925-927

Genes on Demand.International Initiative for Mutation of the Mouse GenomeInstitute of Developmental Genetics

Dr. Cornelia Kaloff

EUCOMM Project Manager,


Genetics

Telephone +49 - 89 / 31 87-22 75

[email protected]

www.eucomm.org

� 34


he “Plant Genome Research” group headed by Dr. Klaus Mayer studied effects and

consequences of so-called poly-ploidization events. The fusion of two different genomes, so-called polyploidization, is very common in plants and occurs rather frequently in the course of evolution. The originally diploid set of chromo-somes can be multiplied. Organisms with tetraploid, hexaploid or octaploid sets of chromosomes are known. During the course of evolution these are often reduced to a diploid set of chromosomes, a typical ploidy state for e.g. animals. As a consequence of iterative polyploidisation and subsequent reorganisation towards a diploid genome often duplicated regions with corresponding genetic infor-mation can be found in the res-pective genome. This also applies to maize, which emerged from an ancestor with a tetraploid set of chromosomes nearly fi ve million years ago.

The GSF scientists compared corresponding, duplicated regions from two maize chromosomes These regions were also compared against the corresponding region in in the rice genome. They addressed questions about similarities and dissimilarities between the dupli-cated maize regions on one hand, and between the regions in maize and rice on the other. Unexpected and very dramatic changes in genome structure have been observed. In maize for parts of the investigated regions individual building blocks were lost, in other

regions building blocks were inserted or rearranged. As a conse-quence, the two corresponding regions are of strikingly different size. However, c lear regularities for these changes cannot be deter -mined yet.

Approx. ten per cent of the genes in the investigated maize regions do not have a corresponding gene in the rice genome and additional 20 per cent are found at different locations in the genome. The genes are surprisingly mobile within the maize genome: 20 to 25 per cent have been relocated to a different site. In the investigated regions two thirds of the original genes located on the tetraploid set of chromoso-mes disappeared .

Thus, due to the remarkable dynamics of polyploidisation and reduplication a high proportion of corresponding genes is located at non-corresponding locations in the genome. Modern plant breeding, which tries to specifi cally breed plants with certain properties, can make use of this insight. Understan-ding the sequence of the genetic building blocks and the dynamics and regularities that shape the maize genome will also be of highest importance to sequence and decode the genomes of important cereal plants such as wheat and barley.

Literature:

� Bruggmann, R., Bharti, A.K., Gundlach, H., Lai, J., Young, S., Pontaroli, A.C., Wei, F., Haberer, G., Fuks, G., Du, C., Raymond, C., Estep, M.C., Liu, R., Bennetzen, J.L., Chan, A.P., Rabinowicz, P.D., Quackenbush, J., Barbazuk, W.B., Wing, R.A., Birren, B., Nusbaum, C., Rounsley, S., Mayer, K.F.X. and Messing, J.: Uneven chromosome contraction and expansion in the maize genome Genome Res., Oct 2006; 16: 1241-1251

“Genome Archaeology”: Evolutionary Changes of Genome Structures in Plants


Dr. Klaus Mayer


Telephone +49 - 89 / 31 87-35 84

[email protected]

T

Duplicated regions in the genome of

maize are evolutionary remainders of

ancient polyploidisation events.

Comparisons of these regions with

corresponding regions in rice give

important clues towards genome

dynamics and plasticity in evolution.

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Thematic Field: Infection and Immunity

-cells provide protective immunity against EBV. CD4+ T-helper cells are a sub-

group of T-cells, that make a major contribution to orchestrating the body‘s immune response. Scientists from the GSF Institute of Clinical Molecular Biology, in collaboration with the Clinical Co-operation Group Paediatric Tumour Immunology, have shown that T-helper cells specifi c for glycoproteins of the virus coat can directly destroy B-cells transformed by EBV. When B-cells are infected, virus coat proteins are left behind on the cell surface. Thus coat protein specifi c T-helper cells can recognise and destroy cells infected with EBV

before virus replication takes place or a latent infection is established.

These results establish the existence of a new role for glycopro-tein specifi c T-helper cells in the control of EBV infection which is very signifi cant for the future development of immunisation strategies.

The identifi cation of viral glyco-proteins as functionally signifi cant antigens in the development of an immune response could also be important for the prevention and therapy of other infections elicited by coated viruses.

Literature:

� Adhikary, D. et al.: J. Exp. Med. 203, 995-1006 (2006)

Identifi cation of Viral Glycoproteins as Functionally Important Antigens

Institute of Clinical Molecular Biology and Tumor Genetics

Dr. Josef Mautner

Clinical Cooperation Groups PTI

Telephone +49 - 89 / 70 99-518

[email protected]

EBV

CD21

Nucleus

Endosome

CD4+

Recognition of EBV-infected B-cells by

glycoprotein-specifi c T-helper cells.

During the infection of B cells, proteins of the viral envelope are retained at the cells surface and subsequently cleaved into peptides in endosomes/lysosomes. These peptides are presented on the cell surface by MHC class II molecules for recognition by glycoprotein-specifi c CD4+ T-helper cells. Glycoprotein-specifi c T-helper cells control the spread -ing of virus infection by lysing EBV-infected cells before the virus is able to replicate in the infected cell.

T

� 36


lg hypermutation

hypermutation

error-pronepolymerase

ubiquitin

abasic site

DNA (Ig gene locus)

PCNA

ur immune system has to fi ght off many pathogens everyday. To do this, the

B-cells in the immune system produce specifi c antibodies that are exactly designed for a particular pathogen. Scientists from the GSF-Institute of Molecular Radiobiology have shown for the fi rst time that a molecular mechanism which usually serves the repair of damaged DNA enables cells of the immune system to produce a great variety of antibodies.

Hypermutation, a millionfold increased natural mutation rate – is elicited by a B-cell specifi c enzyme, AID. This enzyme causes a particular DNA component (a base) to be transformed into a different one. This ‚false‘ base is cut out of the DNA, which leads to a gap. The scientists were able to show that the subsequent steps in hypermutation use a mechanism that is also responsible for the repair of damaged DNA. If the B-cell DNA has gaps, a protein called PCNA is linked with another protein called ubiquitin. This process activates particular emergency repair enzy-mes which fi ll the gap. In B-cells this leads to an increased mutation rate because the activated emergency enzymes are likely to build in a different base, out of the four possible, from the original one – leading to a point mutation. Some point mutations result in an increase in the affi nity of the resultant antibodies against the pathogen so that they can fi ght it off more strongly.

The results show that in the B-cells of the immune system, the pathway of the PCNA-ubiquitinisati-

on is so altered that increased mutation rates occur in specifi c parts of the antibody gene. This is positive on the one hand because it leads to an effi cient increase in the antibody variety. On the other hand, there is the risk that in some cases uncont-rolled mutations on the ‚wrong‘ genes can contribute to the develop-ment of cancer in B-cells.

Literature:

� Arakawa H. et al.: PLoS Biology 4, 1947-1956 (2006)

DNA Repair Mechanisms Optimise One Path in Immune Defence

Institute of Molecular Radiation Biology

Hiroshi Arakawa

Institute of Molecular

Radiation Biology

Telephone +49 - 89 / 31 87-40 77

[email protected]

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ver 95% of the population is infected with Epstein-Barr-Virus (EBV) by the age of 30.

The virus infects the mucous membranes in the nasal cavity and causes glandular fever (infectious mononucleosis or kissing disease). Following the primary infection, the virus can persist throughout life in B lymphocytes, transform these cells into malignant cells, and lead to the development of B cell lymphomas. The transition from latent infection to transformation is an extremely complex molecular process. Scientists from the GSF Depart-ment of Gene Vectors together with colleagues from the University of Wisconsin in the USA have identifi ed a gene region, which is essential for the transformation of B cells.

It has long been known that the gene that codes for the EBV nuclear antigen 1 (EBNA1) is essential for replication of the viral genome within the infected cell. Using

targeted molecular alterations in a region of the EBNA1 gene, it has now been shown that this region is essential for the transcription of several transforming EBV genes. Thus EBNA1 is also critically invol-ved in the transformation of the latent infected cell into a malignant cell.

Thus EBNA1 provides a potenti-ally very interesting target molecule for antiviral and cancer therapy.

Literature:

� Altmann, M. et al.: Proc. Natl. Acad. Sci. USA 103, 14188-14193 (2006)

B-Cell Transformation by Epstein-Barr Virus: Molecular Steps Elucidated in a B-Cell Lymphoma Model Department of Gene Vectors

Prof. Dr.

Wolfgang Hammerschmidt

Department of Gene Vectors

Telephone +49 - 89 / 31 87-15 06

[email protected]

O

Electron micrograph of a viral particle

of Epstein-Barr virus. The well-structured

viral capsid is surrounded by a loose

membrane. The capsid contains the

genetic viral information that can cause

transformation of a cell infected with

EVB.

� 38

Thematic Field: Ecosystems and Health

n a joint project of Stanford University, the Institute of Biochemical Plant Pathology and

the Cologne Max-Planck-Institute for Plant Breeding Research we could show that a mechanism existing in barley for the resistance to mildew may also be functional in other crop plants.

Mildew fungi are economically relevant plant pathogens causing enormous crop losses throughout the world every year. Interestingly enough, conventionally grown mutants of barley with a defect in a particular gene, which, therefore, do not have a functional so-called Mlo protein, are completely resistant to the attacks of the barley mildew. Although this type of mildew resistance of barley was described more than 60 years ago and has been used intensively for 25 years (currently more than 50 % of the

barley grown in Germany is of the MIo type), no other plant species or mutant with a similarly effective immunity to mildew was known until recently. This led to the conclusion that MIo resistance is a barley-specifi c phenomenon.

Now, genetic studies with the model plant thale cress, or mouse-ear cress, (Arabidopsis thaliana) showed that due to the absence of 3 different MIo genes the mildew resistance also works against an Arabidopsis-specifi c mildew in this case.

The signifi cance of this result is that the immunity caused by the absence of MIo, therefore, must have been conserved at least since the phylogenetic split of monocoty-ledonous and diploblastic plants (approx. 200 million years ago). Thus, it should also basically be possible to produce mildew-resistant mutants of any higher plant species.

Literature:

� Consonni, C., Humphry, M., Hartmann, A., Livaja, M., Durner, J., Westphal, L., Vogel, J., Lipka, V., Schulze-Lefert, P., Somerville, S.C., Panstruga, R.: Conserved requirement for a plant host cell protein in powdery mildew pathogenesis. Nature Genetics 38, 716-720 (2006)

Principle of Resistance to Mildew in Barley Can Be Transferred to Other Plants

Institute of Biochemical Plant Pathology

I

Prof. Dr. Jörg Durner

(Acting) Director of the

Institute of Biochemical

Plant Pathology

Telephone +49 - 89 / 31 87-34 34

[email protected]

Mildew-affected barley

The genetically fully decoded wild fi eld

herb Arabidopsis thaliana is often used

as a model to understand processes or

mechanisms in crop plants.

The mildew fungus can also grow on

the model plant Arabidopsis thaliana

(leaf on the right). On the left a leaf of

an Arabidopsis mutant resistant to

mildew.

© M

ax-P

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Res

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mmonium oxidation is the fi rst step in nitrifi cation, a key step in the global

nitrogen cycle which leads to the formation of nitrate. Nitrate is an essential nutritional element for plants. However when nitrate is leached from the soil it can lead to contamination of groundwater, particularly if it is present in high concentrations, which are not used by the plant. Therefore the kinetic of nitrate formation is of great importance.

Until now it was thought that Gram negative bacteria (proteo-bacteria) are mainly responsible for the ammonium oxidation. Scientists from the GSF Institute of Soil Ecology, working with other international research groups, have successfully identifi ed micro-organisms belonging to Archaea as key organisms in this process. These organisms build their own domain in the phylogenetic tree of life besides Bacteria and Eukarya.

As until now none of these organisms has been cultured from soil, molecular and biomarker approaches were used to show the importance of this group of organisms for the transformation of ammonium. It could be shown that in soils from different climatic zones ammonium oxidizing archaea were

more abundant compared to the functional redundant group of ammonium oxidizing proteobacteria and that the appropriate metabolic pathway for ammonium oxidation is induced. Thus archaea, more precise crenarchaeota, are clearly the most common ammonium oxidisers in the global soil system and make a considerably higher contribution to nitrate formation than their bacterial counterparts.

These new fi ndings are very important for agricultural practice, as now it will be possible to look for ways to stimulate the activity of these archaea using targeted agri -cultural management techniques. In this way the application of nitrate fertilisers could be reduced, and with it the resulting potential environmental impact.

New Key Organisms in the Nitrogen Cycle

Institute of Soil Ecology

A

Dr. Michael Schloter


Telephone +49 - 89 / 31 87-23 04

[email protected]

Metabolome(metabolites)

Microbialactivities

Proteome(proteins)

Transcriptome(mRNA)

Genome(DNA)

Turnover process

Microbial

potentials Microbial functions

Interplay between microbial genetic

ressources, geen expression und turnover

processes in ecosystems.

Literature:

� Leininger, S. et al.: Nature 442, 806-809 (2006)

� 40


he question of how bacteria and plants communicate with each other and what

advantages the two sides gain from this is being investigated by a number of GSF Institutes in the fi eld of environment in the project ‚Molecular interactions in the rhizosphere‘. The focus of interest is on N-acylhomoserine lactones (AHL), a group of bacterial signal molecules that root-associated bacteria use to communicate with each other. AHL production is also widespread among human patho-genic bacteria. In addition to the density of the bacterial community, especially the spatial distribution plays a decisive role for communi-cation. A ‚calling distance‘ of up to 78 thousandths of a millimetre was identifi ed on plant roots, more than 50 times the average bacterial cell size. In particular, the occurrence of cell aggregates is decisive for high rates of production of signal molecules. But plants also react to these bacterial signal molecules. The project was able to show that AHL molecules elicit plant defence reactions as well as systemic resistance to damaging fungi. The experimental data are supple-mented by a mathematical model developed by GSF mathematicians and researchers which enables the actual amount of signal substances produced by the bacteria to be

determined in time and space, and the regulatory network involved to be analysed.

The knowledge gained on the communication of bacteria among each other and with other organisms offers a range of applications. In the area of health, new therapeutic substances may be possible based on the destruction of bacterial communication during pathogene-sis. These promise a more sustain-able effect than antibiotics because it is unlikely that resistance would be developed. In agriculture, one possible use that is being investi-gated intensively at the GSF in fi eld experiments is the application of bacteria or their signal substances to control plant diseases or stimulate plant defence mechanisms.

Literature:

� Gantner S. et al.: FEMS Microbiol. Ecol. 56, 188-194 (2006).

� Schuhegger R. et al.: Plant Cell Environ. 29, 909-918 (2006).

Bacteria and Plants in Dialogue – New Insights

Department Microbe Plant Interaction

T

Prof. Dr. Anton Hartmann

Department Microbe Plant

Interaction

Telephone +49 - 89 / 31 87-41 09

[email protected]

N-Acylhomoserin lacton

Experimental determination of the

distances between AHL-producing and

AHL-detecting bacteria at the root

surface using confocal laser scanning

microscopy and geostatistical analysis.

n = 892 Maximum calling distance = 78 um

0 10 20 30 40 50 60 70 80Calling distance = 78 um

150

100

50

0Fre

qu

en

cy

40 45 50 55 60 65 70 75

25 µm4 35 66 95 127

X coordinate (um)

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mmunochemical analysis methods using monoclonal antibodies offer effective and cost

reducing possibilities for the rapid detection of pollutants in environ-mental compartments like water and soils. Scientists from the GSF Institute of Ecological Chemistry and the GSF Institute of Molecular Immunology together developed different monoclonal antibodies for low molecular weight pollutants and used them in various analytical techniques. They can be employed, for example, for direct analysis of pollutants in a sample or during its preparation for further analysis. The main focus is on pollutants like the herbicides Isoproturon or Diuron that are commonly used in Europe. Using these new methods, Isoprotu-ron has been successfully detected with high selectivity and sensitivity (ppt range) in surface water, and Diuron in effl uent from a sewage plant.

A further focus is on the produc-tion of monoclonal antibodies for DDT and its isomers. These new

antibodies were integrated into an optical immunosensor. Using this, DDT was analysed in different water samples, including from the Nairobi River in Kenya. The sensor has the additional potential of being able to analyse a number of compounds simultaneously. The fi rst experi-

ments along these lines have been successful (see Figur).

The technologies developed in this way are not only useful in the fi eld of environmental analysis. There are potential applications in the analysis of foodstuffs, and medical diagnosis. For the latter a new EU project (CARE-MAN) has already started. Among other activities in this project, selective monoclonal antibodies for target structures are being produced that were identifi ed as markers for fi ve main areas of disease (cardio-vascular disease, cancer, thyroid disorders, coagulation disorder, and chronic and acute infl ammation).

Literature:

� Krämer, P.M. et al., in: Rational Environmental Management of Agrochemicals: Risk, Assessment, Monitoring, and Remediation Action. Eds. Ivan R. Kennedy et al., Chapter 12, ACS Symposium Series 966. American Chemical Society, Washington, DC, USA, in press

PD Dr. Petra Krämer

Institute of Ecological Chemistry

Telephone +49 - 89 / 31 87-27 72

[email protected]

I

Dr. Elisabeth Kremmer

Institute of

Molecular Immunology

Telephone +49 - 89 / 70 99-321

[email protected]

The optical immunosensor consists of a bench top instrument (left, shown with open

cover), single-use plastic chips (details, top left), and a laptop (right). The latter is used

for instrument control and registration, storage and evaluation of the results. This

example shows a simultaneous measurement of three analytes (Isoproturon, Diuron,

and Phenothrin). For the selective recognition of the analytes of interest, monoclonal

antibodies (mAbs) – labelled with one fl uorescent dye – are used. Analyte derivative-

protein-conjugates, which are immobilised on the chip surface (spots on the chip, top

left) and analyte in solution compete for the antigen binding sites of the mAbs. Laser

light is used for the excitation of the fl uorescent dye, and the fl uorescence emission is

measured in a photomultiplier. The analyte allocation is carried out through the

position of the signal on the chip surface, see demonstration on the laptop screen

(unpublished results, Master thesis Christina Räuber, IÖC (TUM), 2006).

Innovative Environmental Analysis with Antibodies

Institute of Ecological Chemistry andInstitute of Molecular Immunology

� 42


fforts to destroy tumour cells with the help of the immune system have a long tradition

at the GSF. They began with Professor H.J. Kolb’s pioneering work which showed that donor lymphocyte infusions (DLI) in patients who had undergone allogeneic bone marrow transplan-tation led to a clear regression of chronic myeloid leukaemia (CML), which lasted for many years.

Unfortunately the “graft-versus-leukaemia” effect is often accompa-nied by a “graft-versus-host” reaction, which is often fatal. Furthermore, the DLI approach was most successful for the treatment of slowly growing malignant tumours, such as CML, since in this case enough time is available for a

Adoptive T Cell Therapy: New Perspectives for Translational Research

Institute of Molecular Immunology

E

Immune monitoring

ELISPOT is used to quantify the immune response of specifi c T-lymphocytes using their cytokine production. A colour reaction makes the activated lymphocytes (spots) visible (picture on the right), their number is used as a standard for the reactivity of T cell responses and, thus, allows a standardised assessment of the immune reaction in the course of the therapy.

ELISPOT

before after

developing immune response to gather suffi cient strength for tumour rejection.

In order to stimulate a similarly effective immune response against uncontrolled infections in transplant patients, fast growing leukaemias, or even solid tumours, it is essential to have technologies which enable the rapid generation of antigen-specifi c T-cells on the one hand, and which, on the other hand, also allow large numbers of adoptively

Sterile cell sorting

T-cell receptor analyses

Multiparameter cytometry

Investigation of the T-cell receptor diversity

Identification of special cell populations by antibody staining

Quantification of cytokines and identification of human leukocyte antigens

ELISPOT quantification of the immune response of specific T-lymphocytes using their cytokine production

Live cell imaging

Monitoring Processes in the GSF Platform

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transferred cells to be given to recipients, in order to prevent the both problems of time limits for the development of an effective immune response and the risk of “graft-versus-host” disease. These T-cells need to have receptors with suffi cient avidity to recognise and destroy tumour cells effectively and they should be transferred into an in vivo environment that supports their further expansion, function, and survival. Important breakthroughs during the last few years prove the increasing signi-fi cance of adoptive T-cell therapy for the effective treatment of infections and tumour diseases. However, to achieve the necessary technological development common action is required. Therefore, 14 research groups, seven each from Munich and Berlin, have started their

Prof. Dr. Dolores J. Schendel

Director of the Institute of

Molecular Immunology

Telephone +49 - 89 / 31 87-301

[email protected]

collaboration in a transregional collaborative research centre (SFB-TR) with the aim of defi ning the ‘Principles and Applications of Adoptive T Cell Therapy‘. Thomas Blankenstein from Berlin und Dolores Schendel from Munich are coordinating this SFB-TR, which was offi cially initiated in July 2006. Six of the Munich projects are led by GSF scientists, demonstrating the competence of the GSF in this area of research. The activities of the SFB-TR are fully embedded in the GSF research programme. They supplement the clinical objectives of a number of clinical co-operation groups and are fi rmly focused on future developments in ‘Immune Monitoring‘.

For this reason this joint SFB-TR initiative broadens the GSF’s efforts to further promote cooperation with local university hospitals in the long run, thereby opening up possibilities for an exciting new era of the immune therapy of tumours and infectious diseases, with the aim of transferring fundamental research into the hospitals and even opening up therapeutic concepts for diseases like asthma, allergy and autoimmu-nity in the future.

� 44


eukaemias are due to disturbed blood formation in the bone marrow, an excessive pro-

duction of immature cells with no function. It is the aim of the therapy to destroy the degenerate cells in the bone marrow and replace them with healthy blood forming cells of a donor. In 1975 the current head of the Clinical Cooperation Group (KKG) “Hematopoietic Cell Trans-plants”, Prof. Kolb, carried out the fi rst successful bone marrow transplantation in Germany together with colleagues from the Munich Schwabing Hospital. T-cells which trigger a dangerous immune reaction of the donor against the recipient, can be removed from the donated bone marrow beforehand. Before the purged donor bone marrow can be transplanted, the patient’s diseased bone marrow must be destroyed. This is done by radiation and chemotherapy.

Unfortunately even after most intensive radiation and chemo-therapy individual leukaemia cells are left in the organism, which means that the disease can fl are up again (relapse), if the T-cells were removed. So there is a dilemma between the reaction against healthy organs of the patient on the one hand, a graft-versus-host reaction which can destroy the skin, the intestine and the liver and must,

Fighting Cancer with the Immune System

Clinical Cooperation Group Hematopoietic Cell Transplants

L therefore, be avoided, and the reaction against the patient’s leukaemia, which is highly desirable. A solution to this dilemma was suggested by experiments on dogs, in which the blood formation of the recipient is switched off by the transfusion of lymphocytes of the donor 2 months and later after the transplantation of T-cell-deprived bone marrow, without triggering a graft-versus-host reaction.

This principle could be success-fully applied in patients with relapsing leukaemia; as soon as chimerism and immune tolerance had been induced, donor lympho-cytes could be transfused to treat the relapsed disease, without causing a severe graft-versus-host reaction. These donor T-cells recognise the leukaemia cells as being foreign cells and destroy them without the need for more radiation

isotype control anti-canine CD34

Day 0

Day 6

Day 9

CD

34

0.11 0.16

1.24 64.13

3.96 65.88

Expression of stem cell antigen CD34 after coculture with the

mouse cell line OP9

Production of

hematopoietic stem cells

from embryonic stem cells

in dogs.

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or chemotherapy. Although chemo-therapy and irradiation are still indispensable to the preparation of any bone marrow transplantation, the KKG could show that the quantity and thus the burden on the patient can be reduced considerably by subsequent adoptive immune therapy. The principle of immune therapy with T-cells from a healthy donor – after the establishment of the immune system of the donor from the stem cell transplantation – is also suitable for the treatment of other types of tumour diseases. However, the immune reaction against other types of tumour must be facilitated, since these are more diffi cult to recognise and attack than leukaemias. Tumour-specifi c anti -bodies and T-cells, but also T-cells armed with specifi c receptors by genetic therapy, can be used to destroy degenerate cells. Genetic therapy basically offers excellent possibilities for the treatment of leukaemia and malignant tumours, in the case of congenital diseases the disease gene can be replaced by a healthy gene in stem cells. But genetic therapy must also be further developed in animals similar to humans to reach a stage at which it can be applied to human patients effectively and without any severe complications.

Literature:

� Schmid, C., Schleuning, M., Schwerdtfeger, R., Hertenstein, B., Mischak-Weissinger, E., Bunjes, D., Harsdorf, S.V., Scheid, C., Holtick, U., Greinix, H., Keil, F., Schneider, B., Sandherr, M., Bug, G., Tischer, J., Ledderose, G., Hallek, M., Hiddemann, W., Kolb, H.J.: Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood. 2006 Aug 1;108(3):1092-9. Epub 2006 Mar 21.

8.0%

tetramer control

Donor

Patient

day 3

Patient

day 6

Patient

day 10

0.4%

2.3%

5.3%

CD

8

Tetramer

GLC/HLA-A2

(BMLF1)

Expansion of

EBV-specifi c T-cells

in vivo.

Prof. Dr. Hans-Jochem Kolb

Telephone +49 - 89 / 70 95-42 41

[email protected]

� 46


hronic obstructive pulmonary disease (COPD) leads to a progressive reduction in

pulmonary function. This can result in severe breathing diffi culty due to narrowing of the airways and destruction of lung tissue. Smoking is the major risk factor, but in the developing countries the inhalation of smoke from the open fi replaces in poorly ventilated rooms is an additional factor. According to the World Health Organization (WHO), COPD is the fi fth most common cause of death world-wide, and it will be the fourth most common

cause by 2030. Approx. fi ve million people are estimated to be currently affected by the disease in Germany.

Patients with COPD have an increased susceptibility to lung infections. These infections result in the further deterioration of the lung structure and function. For this reason, vaccinations against infl uenza and pneumococci are recommended in order to protect COPD patients from these infections. With the common vaccination methods against pneumococci,

New Vaccination Strategy for the Prevention of Infections in Chronic Pulmonary Diseases

Clinical Cooperation Group ‘Infl ammatory Lung Diseases‘

C however, only a partial protection can be achieved.

The Clinical Cooperation Group ‘Infl ammatory Lung Diseases‘ is working on an innovative procedure for introducing vaccines directly into the lung by means of inhalation. This involves the generation of an aerosol from the liquid vaccine and the use of the AKITA device, which ensures controlled breathing during inhalation (AKITA® = “Apparatur zur kontrollierten Inhalation therapeu-tischer Aerosole“ (device for the controlled inhalation of therapeutic aerosols), see picture). This ap-proach leads to optimum deposition of the vaccine in the lung. The KKG has conducted previously two randomised studies with this method: a fi rst one with healthy volunteers (Menzel et al) and a second one with COPD patients (see Meyer et al).

Inhalation of a vaccine: in

the new vaccination strategy

the vaccine is atomised and

inhaled. The AKITA device

(in the front) ensures that the

inhalation proceeds slowly

and that the vaccine is ideally

deposited in the lung.

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These studies showed good tolerance of the inhalative vaccina-tion: The most frequent side-effects were fatigue and a slight rise in body temperature. These are, however, desired reactions, which are due to a strong immune reac-tion.

This strong immune reaction was then also manifested in a good antibody response to the sugar structures of the pneumococci. When the immunoglobulin G antibody response in the blood of the COPD patients was measured, the reaction following inhalative immunisation was comparable to the reaction seen after the commonly employed intramuscular injection.

Streptococcus pneumoniae

This project was carried out by the Clinical Cooperation Group in cooperation with the Asklepios Fachklinik für Pneumologie in Gauting near Muenchen and the spin-off company Inamed, also Gauting. The aim of the inhalative vaccination strategy is not only to generate a systemic immuno-globulin G response , but also to develop a potent specifi c local immunity in the lung.

Therefore, follow-up studies will investigate the development of local immunity, i.e. the formation of Immunoglobulin A. Immunoglobulin A is THE CRUCIAL DEFENCE MOLECULE found on the mucous membranes of the lung and in saliva. Therefore, in this new study samples of saliva are taken before and after the vaccination, which are then analysed for IgA directed against pneumococci. If this

additional development of local immunity is successful, the inhala-tion vaccina tion of COPD patients can be extended to include other microbial pathogens and help protect these patients more effi ciently from life-threatening infections.

Literature:

� Menzel, M., Muellinger, B., Weber, N., Haeussinger, K., Ziegler-Heitbrock, L.: Inhalative Vaccination with Pneumococcal Polysaccharide in Healthy Volunteers, Vaccine, 23: 5113, 2005

� Meyer, P., Menzel, M., Muellinger, B., Weber, N., Haeussinger, K., Ziegler-Heitbrock, L.: Inhalative Vaccination with Pneumococcal Polysaccharide in Patients with Chronic Obstructive Pulmonary Disease, Vaccine, 24: 5832, 2006

Prof. Dr. med. Ziegler-Heitbrock,

Head Clinical Trials

Telephone +49 - 89 / 31 87-18 89

[email protected]

Pneumococci in the blood

The red circles are the red blood cells, and the dark blue dots are the

pneumococci, which are typically found in pairs. This historical picture was

taken from Muir‘s Bacteriological Atlas, van Rooyen, published by

Livingstone, Edinburgh, 1937.

� 48

General Development

s a research institution of the Federal Republic of Germany and the Free State

of Bavaria, the GSF is a member of the Helmholtz Association1, Germany‘s biggest public research organisation. It investigates the foundations of the medicine and medical care of the future as well as ecosystems of substantial signi-fi cance to health. The GSF has existed since 1960 and it has been a GmbH (German limited liability company) since 1964.

Its bodies are the Assembly of Partners, the Supervisory Board, the Board of Directors and the Scientifi c and Technical Board. By appointing members to the Supervisory Board and to the Scientifi c and Technical Board the scientifi c and technical staff are also involved in funda-mental decisions. On scientifi c questions the institution also obtains the advice of the Scientifi c Advisory Board, which consists of external members.

PartnersThe partners of the GSF 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 Finances.

Necessary funding is provided by the federal government and the government of Bavaria (in the latter case by the Bavarian Ministry of Education, Science and the Arts) at a ratio of 90 : 10 in accordance with the Framework Agreement on Research Promotion (Rahmen-vereinbarung Forschungsförderung) of 28/11/1975 and the Implementa-tion Agreement of 26/6/1978.

As an exception to this arrange-ment the federal government pays all the funds required for the ASSE Research Mine in Lower Saxony as well as for the GSF‘s activities as a project agency of the BMBF (PT-GSF).

Supervisory BoardThe Supervisory Board oversees the lawfulness, appropriateness and economic effi ciency of the manage-ment. It decides upon general research objectives and on impor-tant matters of research policy and fi nancial matters of the GSF. It lays down the basic principles for performance control. The Supervi-sory Board is composed of 12 honorary members.

The Supervisory Board has the following members:

MinDir Dr. Peter Lange –Chairman of the Supervisory Board –Federal Ministry of Education and Research

MinDirig Dr. Adalbert Weiß –Deputy Chairman of the Supervisory Board –Bavarian State Ministry of Science, Research and the Arts

MinR Klaus HerzogBavarian State Ministry of Finance

MinDirig Dr. Karl Eugen HuthmacherFederal Ministry of the Environment, Conservation and Reactor Safety

MinR Hermann RiehlFederal Ministry of Education and Research

Prof. Dr. M. GrasserbauerDG Joint Research Centre / Institute of Environment and Sustainability

Dr. Harald SeidlitzDepartment of Experimental Environment Simulation of the GSF

Prof. Dr. Joachim GrawInstitute of Developmental Genetics of the GSF

Dr. Andrea KleinschmidtInstitute of Molecular Virology of the GSF

General Development

A

1 Helmholtz-Gemeinschaft Deutscher Forschungszentren e. V.

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Scientifi c Advisory BoardThe Scientifi c Advisory Board advises the GSF� on fundamental scientifi c issues

and in connection with taking on new tasks,

� on the research and development programme, including the required fi nancial planning,

� on questions of cooperation with universities, other research institutions and international institutions.

The Scientifi c Advisory Board has the following members:

Prof. Dr. Yves-Alain Barde,Division Pharmacology, Neurobiology, Biocentre, University of Bâle

Prof. Dr. Heiko Becher,Hygiene Institute, University of Heidelberg

Prof. Dr. Thomas Bieber,Hospital and Out-Patient Clinic of Dermatology, University Hospital of Bonn

Prof. Dr. Maria Blettner,Institute of Medical Biometry, Epidemiology and Informatics, University of Mainz, Deputy Chair

Prof. Dr. Bernd Dörken,Med. Clinic with a Focus on Oncolo-gy – Haematology – Tumour Immu-nology, Charité University Medicine, Campus Buch, Robert-Rössle-Klinik; Berlin

Prof. Dr. Martin H. Gerzabek,Institute of Soil Research, University for Soil Culture Vienna

Prof. Dr. Manfred GrasserbauerDG Joint Research Centre – Institute for Environment and Sustainability, Ispra (Italy), Chairman

Prof. Dr. Peter Herrlich,Leibniz Institute of Age Research (Fritz-Lipmann-Institute e.V.), Jena

Prof. Dr. Reinhard Kurth,Robert-Koch-Institut, Berlin

Prof. Dr. Dieter Mayer,Aventis-Pharma, Idstein

Prof. Dr. Wolfgang-Ulrich Müller,Institute of Medical Radiation Biology, University Hospital of Essen

Prof. Dr. Dierk Scheel,Leibniz Institute of Plant Biochemistry, Halle

Prof. Dr. Sylvia Schnell,Institute of Applied Microbiology, University of Gießen

Prof. Dr. Hans R. Schöler,Max-Planck-Institute of Molecular Biomedicine, Münster

Prof. Dr. Gerhard Schultze-Werninghaus,Berufsgenossen-schaftl. Kliniken Bergmannsheil Hospital of the Ruhr University, Bochum

Prof. Dr. Martin Vingron,Max-Planck-Institute of Molecular Genetics, Berlin

Scientifi c and Technical BoardThe Scientifi c and Technical Board (WTR) acts as a consultant to the other bodies of the institution on all scientifi c and important technical questions. The decisions and recom-mendations of the WTR are pre-pared by a Permanent Committee which can also be assigned to deal with certain tasks independently.

The Directors of the Institutes as well as elected representatives of the scientifi c and technical employ-ees are on the WTR. The Board Members and a member of the workers‘ council participate in the WTR meetings in an advisory capacity.

WTR Members (as of 1/4/2007):

Prof. Dr. Martin Göttlicher – Chairman

Prof. Dr. Rainer Meckenstock – Deputy Chairman

PD Dr. Michael John Atkinson

Dr. Joachim Altschuh

Prof. Dr. Georg W. Bornkamm

Prof. Dr. Ruth Brack-Werner

Prof. Dr. Jean-Marie Buerstedde

Dr. Ingo Drexler

Prof. Dr. Jörg Durner (acting)

Prof. Dr. Dr. Karl-Hans Englmeier (acting)

Prof. Dr. Magdalena Götz

Prof. Dr. Wolfgang Hammerschmidt

Prof. Dr. Anton Hartmann

Prof. Dr. Heinz Höfl er

Dr. S. Hoelter-Koch

� 50

General Development

Prof. Dr. Martin Hrabé de Angelis

Dr. Berit Jungnickel

Dr. Jan Christian Kaiser

Dr. Arnd Kieser

Prof. Dr. Rupert Lasser

Prof. Dr. Reiner Leidl

Dr. Esther Mahabir-Brenner

Prof. Dr. Thomas Meitinger

Prof. Dr. Hans-Werner Mewes

Dr. Gabriele Möller

Prof. Dr. Jean Charles Munch

Prof. Dr. Dr. Herwig Paretzke

Prof. Dr. Michael Sattler

Dr. Uta von Rad

Dr. Peter Reitmair

Prof. Dr. Dolores Schendel

Prof. Dr. Jörg Schmidt

Dr. Philippe Schmitt-Kopplin

Prof. Dr. Peter Schröder

Dr. Sigurd Schulte-Hostede (acting)

Prof. Dr. Holger Schulz (acting)

Andreas Stampfl

Prof. Dr. Dr. H.-Erich Wichmann

Prof. Dr. Wolfgang Wurst

Board of Directors

The Board Members are the legal representatives of the GSF and do business according to the Partner-ship Agreement, the resolutions of the Assembly of Partners and the Supervisory Board. In cooperation with other bodies they develop the initiatives required to fulfi l the GSF‘s tasks in planning, coordination and control and ensure the effective and economically viable allocation of funds.

� Scientifi c and Technical Director:Prof. Dr. Günther Wess

� Administrative Director: Dr. Nikolaus Blum

Project Funding

In the year under review of 2006 the fi nancial volume of the GSF was € 154 million with institutional funding of € 91 million and third-party funds of € 63 million. The third-party subsidies for research projects amounted to € 22 million, which is 24% of the institutional funding. The remaining third-party funds were for special tasks (Asse, project sponsorship, evaluation facility, training). In 2006 a total of approx. 270 funded research projects were handled in the GSF‘s research programmes. Apart from contracts with the GSF as a single partner, some of the projects showed a high degree of networking with consortium partners. These include, in particular, the research projects with the European Commis-sion and nationally funded projects, such as the National Genome Research Network (NGFN), the special DFG research programmes as well as some measures initiated by the Helmholtz Initiative and Networking Fund. With a subsidy of € 4.7 million, EU funding is still the largest portion of international funds raised, thereby making a fundamental contribution to the formation of the European Research Area and the solution of the essen-tial European research questions.

There are currently 60 ongoing agreements with the EU. The successful participation in the 6th Framework Programme for Re-search resulted in an increase in grants in 2006 over the previous years of 2004 (€ 3.4 million) and

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General Development

2005 (€ 3.9 million). After the conclusion of the 6th Framework Programme it can be said that the funds raised increased considerably from € 14 to 25 million over the 5th Framework Programme for Research. The approval rate also increased from 28% to 33% of the applications fi led. The increase in funds raised was mainly for projects in the fi elds of life sciences, food quality and safety as well as the EU mobility measures, accompanied by a simultaneous drop in Euratom subsidies. As a coordinator the GSF successfully started the EU project under the acronym ‚EUCOMM‘ in 2006. The integrated project has a funding volume of € 13 million, with the GSF‘s share amounting to € 3.7 million. The aim of the project is to create a functional European platform for mouse mutants for research into human diseases and it is embedded in numerous other EU projects.

The GSF participates in the funding programmes of the Helm-holtz Initiative and Networking Fund by providing substantial input. In the 2006 tender for Virtual Institutes, i.e. cooperative projects between Helmholtz Centres and universities, the GSF was awarded a research project on neurological diseases and signs of aging of the central nervous

system. Furthermore, two special professorships for outstanding woman scientists have been gained in the framework of excellence assurance. Two approved re-entry positions after child-care periods contribute to more equal opportuni-ties.

Apart from project funding, new cooperation projects have been initiated on a national and internatio-nal level to heighten the competi-tiveness and excellence of the GSF and to establish an important basis for raising project subsidies in the future. There are special coopera-tion contracts with various organi-sations already, such as with the International Atomic Energy Agency (IAEA), the International Commis-sion on Radiological Protection (ICRP), the US Environmental Protection Agency (EPA), the National Institutes of Health (NIH), the Health Protection Agency and the RIKEN Centre for Developmental Biology in Japan or NACIS (Central Iron & Steel Research Institute). Apart from this, there have been talks with representatives of the National Institute of Environmental Health Sciences (NIEHS) in the US in order to identify potential coope-ration projects. The GSF is currently engaged in approx. 900 internatio-nal cooperation projects with uni versities and non-university research institutions in more than 53 countries of the world as a result of sponsorship and cooperation contracts and the bilateral exchange between scientists on guest stays, joint studies and publications.

Human Resources

As of 31/12/2006 the GSF had 1740 employees (previous year: 1725). The number of employees fi nanced by the basic fi nancing has dropped by nine to 1169. The number of employees funded by third parties has increased by 24 to a total of 571. This means that approx. 33 percent of all employees are funded by third parties.

Temporary employment con-tracts were entered into with 854 employees. This amounts to approx. 49 percent. Among the staff paid for by basic fi nancing, employees with temporary employment contracts make up approx. 36 percent.

The number of employees has mainly continued to increase in the scientifi c area (see Fig. structure of GSF employees by areas).

The largest number of scientists work in the areas of biology, chemistry, physics and medicine (see special fi elds of the GSF scientists).

It is very positive to see that the ratio of women among the scientists is rather high at 44 percent. The reasons for this are our openness towards to part-time employment and the higher rate of junior woman scientists employed. Reduced weekly working hours are agreed with 15 percent of our employees. 55 percent of our junior scientists and postgraduate students are women (previous year 48 percent) and 51.3 percent of the overall GSF payroll are women.

� 52

General Development

Advancement of WomenIn the Helmholtz Programme for the re-entry of scientists to work after family-related leave under the President‘s Initiative and Networking Fund, two female scientists were employed with the GSF for three years starting in 2006. Helmholtz can also fund positions for excellent woman scientists (W2/W3 posi-tions), in order to win them over permanently for the Centre in good positions. The GSF successfully applied for the funding of two outstanding woman scientists and their teams for the duration of fi ve years.

The improvement of opportuni-ties for women and the support of young scientists is also the focus of the EU project “Pallas Athene – Ambassodors for Women and Science”, in which the GSF partici-pates alongside other Helmholtz Centres. Excellent woman scientists act as “Ambassadors”, presenting their research results at different types of events and promoting an interest in science among young people, particularly women.

In its Junior Scientists‘ Pro-gramme the GSF gives young scientists the possibility to run their own teams. To specifi cally further women, a second junior group has been announced in addition to an already existing group, which was given a woman as a team leader in 2006.

Child Care

The GSF is also still committed to looking after employees‘ children on its own property in the associati-on “ganz schön frech” (very chee-ky), which was established by GSF employees, and which runs the GSF‘s own child care centre for approx. 25 children from the age of eight weeks to six years.

Further TrainingThe GSF supports the further vocational training of its employees by offering a wide range of approp-riate internal and external training courses. In the 2006 training programme the focuses were on management, communication and personal development as well as technical operational subjects, EDP and language courses. 50 in-house seminars/courses and more than 300 external training measures were approved.

Advancement of Junior Scientists

Postgraduate Students

Postgraduate students at the GSF work on highly topical questions in an excellent scientifi c environment. They make a substantial contribu-tion to the success of our research centre, so ensuring they are given the best possible training and excellent working conditions is a top priority. In order to further young scientists even more specifi cally, we have developed a comprehensive postgraduate programme coordi-nated by mentors in the four major fi elds of the GSF. Apart from the basic prerequisite that each post-graduate is given scientifi c support

by scientists during the entire duration of the work on their thesis, a number of subject-related, inter-institute and inter-programme events are offered in the postgradu-ate programme. Apart from intro-ductory presentations on research targets, institutes and technologies of the GSF, these include various subject-related courses such as summer and winter schools, and seminars in rhetoric, project management, the protection and marketing of research results, applying for grants, writing publica-tions and many other things. Once a year closed meetings are offered outside the GSF, at which the postgraduate students can present their results and discuss them with experts. Furthermore, each post-graduate has the possibility to present the results of his or her work to a broad expert audience at national and international work-shops or conferences. In addition to this, subsidies are granted which allow visits to national or European workshops and conferences from the very beginning of work on a thesis. This gives the postgraduates an early insight into the scientifi c environment of their fi eld or neighbouring fi elds. They are actively involved in the scientifi c life of the GSF from the beginning and can benefi t from the centre‘s interdisciplinary approach.

The total number of postgradu-ates employed in 2006 (376, of which 231 were sponsored by third parties and universities), which went up again, goes to show that the GSF was able further enhance its attractiveness for qualifi ed post-graduates with its postgraduate programme.

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The Association of the Friends and Sponsors of the GSF awards the annual postgraduate prize of € 1500 for excellent scientifi c performance and the extraordinary commitment of postgraduates together with the Genossenschaftsverband Bayern (cooperatives‘ association of Bavaria). Three outstanding theses win the award in the fi elds of environmental and health research. The prize is awarded at the institute forum, the highlight of the GSF‘s scientifi c year.

Trainees

As of 31/12/2006 the GSF employed 72 trainees in Neuherberg and in Remlingen. The focuses were on training in the following professions: biology laboratory assistant, animal nurse, offi ce clerk, industrial mechanic, energy electronics expert, Dipl.-Ing. (BA) in the fi eld of radia-tion protection and environmental technology, warehousing specialist, computer specialist and agricultural assistant.

Voluntary Ecological Year

Since 1995 the GSF has been recognised as an institution for the voluntary ecological year. The voluntary ecological year offers young women and men between the ages of 16 and 27 the possibility to fi nd out where their main inte-rests lie by working for a year as a volunteer in an institution of conservation and environmental protection or environmental educa-tion before embarking on a career. The practical work is accompanied by a training programme run by the German Catholic Youth Federation (BDKJ).

Every year the GSF offers positions for the voluntary ecologi-cal year and is the leader in Bavaria in this fi eld. In 2006/2007 four positions were occupied, and fi ve participants have already been marked down at the GSF for 2007/2008.

Internships/Work Experience

Internships alongside work or studiesInternships are possible at the GSF, in particular trial internships for professional orientation during and after school education as well as compulsory internships for various courses of study.

Work experience – diploma students – postgraduatesAt the GSF, pupils and students continue to have the possibility to gather practical experience in all scientifi c fi elds for their fi rst steps into their working lives, to get an insight into the scientifi c world and to benefi t from contacts with scientists for their future careers as scientists.

Pupils’ Forums

Since 1998 the GSF has been offering “Pupils‘ Forums” to the science pupils at Bavarian high schools. In the 2005/2006 school year, southern Bavarian high schools were invited. The aim of the one-day events is to show these young people the working environ-ment in research and to attract them to it. In the morning, general presen-tations provide a theoretical back-ground, and in the afternoon laboratory visits are offered. The curricula of these events was determined together with teachers and scientists. The Pupils‘ Forums are very popular with both pupils and teachers alike. In 2006 more than 700 pupils and their teachers attended seven of these events at the GSF.

The Glass Laboratory

More than 3000 people visited the glass laboratory in the year under review. The focus of a day of experiments in the glass laboratory is on one of the many fi elds that the GSF National Research Centre works on. The experiments are prepared so as to be interesting for school pupils and so that they can do the experiments themselves.

� 54

General Development

In order to also give the target group of Realschule secondary school pupils an insight into scientifi c work, a new “Chemical Reactions” internship was offered last year in cooperation with the Chemistry Work Group. The numerous enquiries about this internship clearly indicate the enormous interest in this practical learning experience.

“Volunteer” scientists outside the class plan have the opportunity to slip into the white coat and get a feeling for a day in the laboratory by engaging in various experiments. These include Girls and Technology, Girls‘ Day, ESOF2006 Helmholtz pupils‘ laboratories and the Munich Science Days, Art at the Scheyern facility, Mini-Munich and vacation

programmes. This year the integra-tion of kindergartens into the programme was a new experience, introducing the pre-schoolers to science with a playful approach.

In November 2006, the Glass Laboratory of the GSF-National Research Center launched a coope-ration with the Bertolt-Brecht-Gymnasium, a high school for girls with a focus on economics and social sciences, with a long-term project for sustainable basic scien-tifi c education and the goal of showing women as professional role models. Here, young girls are offered the opportunity to expe-rience modern research in real life. Initially, a continued cooperation between the pupils of the Bertolt-Brecht-Gymnasium and the GSF-National Research Center for Environment and Health is planned over fi ve school years. This school year the 32 pupils of Class 5a learned to look at the subject of “Light and Life” from different angles in a project week at the GSF. To prepare for this event, the pupils carried out measurements in class from November 2005 to February 2006 and investigated the relation-ship between temperature and light.

The Carl Friedrich von Martius

Environment Prize

Since 1984 the GSF-National Research Center for Environment and Health has awarded the “Carl Friedrich von Martius Environment Prize for Scientifi c Papers” together with the Bavarian Volks- und Raiffeisenbanken and the Associati-on of the Friends and Sponsors of the GSF, in order to support young people‘s dedication to topic relating to the environment and health. The Prize is awarded in memory of the life‘s work of the Bavarian tropical scientist and physician Carl Friedrich Philipp von Martius. It is under the patronage of the Bavarian Ministry of the Environment, Health and Consumer Protection and has a total prize money of € 7500. 101 papers were submitted for the 2006 compe-tition. The awards ceremony was in June. The ten prize winners came from Munich and the Munich area, Upper Bavaria, Lower Bavaria, Swabia, Central Frankonia.

The GSF and the municipal

Bertolt-Brecht-Gymnasium in Munich

jointly developed a project for sustain-

able basic scientifi c education. Under

the motto “School goes Research” the

pupils of Class 5a worked on the subject

“Light and Life” both in class and in a

project week at the GSF.

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General Development

Financial Development in 2006In 2006 the basic fi nancial support from the Free State of Bavaria and the federal government plus own profi ts were down by approx. € 3.17 million as compared to 2005. The reasons are the following: personnel costs rose by approx. € 0.90 million, the physical resources budget was reduced by € 3.47 million year on

Planned budgets 2004 2005 2006

€ million € million € million

HR 52.88 50.10 51.00

Physical resources 25.79 24.70 21.23

Grants/subsidies 3.20 3.30 3.20

Investments 12.70 13.88 14.24

Construction and procurements > 2.5 million 5.39 6.75 5.90

Total expenses 94.57 98.74 95.57

Own profits 8.75 7.60 3.10

Grants Federal / Bavarian 91.21 91.14 92.47

Total funding 99.96 98.74 95.57

Institutional funding:

Income / Grants 2004 2005 2006

€ million € million € million

Federal government (basic financing) 81.56 80.34 81.22

Bavaria (basic financing) 8.15 8.93 9.02

Third parties (basic financing) 0.27 0.28 0.22

Total (basic financing) 89.98 89.55 90.46

Federal government (third-party funds) 38.10 38.80 43.70

European Union 3.40 3.90 4.70

Third parties 7.30 16.00 15.00

Total (third-party funds) 48.80 58.70 63.40

Own profits (basic financing) 8.60 5.81 2.30

Own profits (third-party funds) 6.82 16.00 14.30

Total (own profits) 15.42 21.81 16.60

Total income 154.20 170.06 170.46

year and the budget for grants and subsidies (Clinical Cooperation Groups) was reduced by 0.1. Apart from that, investments were increased by € 0.36 million, while construction and procurements > 2.5 million were reduced by € 0.85 million.

In the budgets planned for 2005 and 2006 the increases and reduc-tions in the individual areas as of 31/12 were as follows:

The following data (as of 07/03/2007) are the actual data and include both the institutional and third-party

funding of the GSF. The GSF budget was fi nanced as

follows:

The GSF‘s expenses are as follows:

In 2006 total HR costs (as of 07/03/07) amounted to € 74 million (previous year: € 78.2403 million).

The portion of HR expenses in total expenses amounts to approx. 47.17 percent (previous year: 47.60 percent). In the basic fi nancing the percentage is 53.36 (previous year: 50.74 percent).

The total cost of materials (including grants and subsidies) were reduced by € 12.258 million from € 63.484 million to € 51.225 million and amount to approx. 32.66 percent (previous year: 38.62 percent) of total expenses. When looking only at the basic fi nancing, expenses were reduced from € 28 million to € 24.425 million in 2006, i.e. by € 3.574 million. This also includes the grants and subsidies of € 3.20 million.

Total expenses for current

investments amount to € 25.743 million, i.e. 16.41 percent (previous year: 9.67 percent) of total expenses. The expenses for current invest-ments in basic fi nancing (previous year: € 13.884 million) increased to € 14.243 million.

Construction projects and procurements > 2.5 million amount to € 5.90 million (previous year: € 6.751 million).

� 56

General Development

Communication

The GSF endeavours to communi-cate its targets and visions both to external target groups and its own employees and to continue to discuss these with them. The focus is on communicating the issues and results in line with modern forms of knowledge management to the respective target groups. Wherever possible, the GSF wants to give substantiated answers to current questions from the public, present-ing problems and their solutions objectively from a scientifi c point of view.

It is of great importance to the GSF to use various modes of successful corporate communica-tion to interest young people in the sciences as well as to attract the attention of outstanding young scientists, provide further training for them or employ them, in order to be successful together. It is a welcome side-effect that these activities also help improve the GSF‘s image.

Some Outstanding Examples

for 2006

Under the motto “Chernobyl – 20 Years On” the GSF organised an excursion for journalists. From 20 to 25 March, journalists from Stuttgar-ter Zeitung, Süddeutsche Zeitung, Die Welt, TAZ and ZDF television as well as freelance journalists and scientists from the Society for Plant and Reactor Safety (GRS) and the GSF travelled from Minsk to Gomel and on to Chernobyl and Kiev.

In autumn 2006 the Munich Re Foundation and the GSF extended an invitation to a series of evenings, each devoted to a particular subject: more than 500 interested Munich citizens discussed current minor and major, real and alleged risks to the population of Munich with high-ranking scientists. At the end of the series the role of politics and the media was scrutinised in the risk debate.

Minister Christa Stewens started off the initiative “Women in Science – Science for Women” on 11 July 2006, the purpose of which was to

draw more attention to the work done by woman scientists and give them more support. The initiative named by the Greek goddess of wisdom “Pallas Athene” is part of a programme subsidised by the European Union with a total of € 220,000 under the category of Science and Society, in which the GSF-National Research Center for Environment and Health participa-ted alongside fi ve other centres of the Helmholtz Association.

The GSF-National Research Center for Environment and Health and Munich‘s Bertolt-Brecht- Gymnasium started a joint project on sustainable basic scientifi c education: 32 pupils from Class 5a visited the GSF in February 2007 to consider the subject of “Light and Life” from different angles during a project week. The cooperation is designed to go on for 5 years and will be scientifi cally assessed.

On 19 December, well-known experts discussed the question “Ethics – a Matter of Perspective?” at the GSF-National Research Center for Environment and Health on the

The group of journalists in front of the sarcophagus

Gen

eral

Dev

elo

pm

ent

57 �

General Development

Minister of State Christa Stewens

(centre) started the initiative “Women

in Science – Science for Women”

on 11 July.

occasion of the Science Future Forum. In this series of events the GSF faces the social issues resulting from scientifi c work. Prof. Dr. Jürgen Mittelstraß (University of Con-stance), Prof. Dr. Herwig Hulpke (formerly Bayer AG), Prof. Dr. Friedrich Wilhelm Graf (LMU) and Prof. Dr. Klaus Peter (LMU) partici-pated in the panel discussion.

With specifi c communication focuses for selected target groups the GSF continued its various series of publications in 2006. Among other things the following subjects were adapted in the form of brochures for the broad public:

“Radiation – from Röntgen to Chernobyl” is the title of the new issue of the GSF magazine mensch+umwelt spezial, which informs the interested public on fundamental issues of the effects and risks of ionising radiation.

Another publication was the brochure “Vom Labor in die Klinik – Translationale Forschung in der GSF” (From the Laboratory to the Clinic – Translational Research at the GSF), which offers the latest information on how the GSF transfers its insights from funda-mental research into clinical applica-tions – and how it conversely integrates expertise from hospitals into its biomedical research work. This is a very essential approach by which the GSF wants to make a decisive contribution in the search

for effective mechanisms all the way to their application for patients.

In the Internet the concept of no barriers was successfully implemen-ted. The number of hits increased to an average of 800,000 per month.

Other fi elds of activity in the communication of science were, e.g., congresses and scientifi c events, training and discussion events for opinion leaders, press releases and background talks with journalists and politicians.

The diversity of these activities in the communication of science has certainly contributed to the fact that the GSF can consider itself one of the leading research institutions in the world in the fi eld of environ-ment-related diseases.

� 58

General Development

ince 1965 the GSF-National Research Center has been operating the Asse Research

Mine near Remlingen. Since this date research and development work on the fi nal storage of radio-active waste in salt formations has been conducted at this former salt mine. Since 1979 no additional radioactive waste has been placed in storage here. Since the GSF-National Research Center has no further requirement for research at the Asse Mine, the mine is now being prepared to close down pursuant to the Federal Mining Law.

A closing-down operation plan has to be submitted to the approval

authority. In the operation planning procedure evidence of the long-term safety is not explicitly required, but it must be ensured that the protec-tion of the surface, i.e. our living space, will still be guaranteed after closing down. Since radioactive waste was deposited in the Asse Mine between 1967 and 1978, the protection of our living space extends not only to any conceivable effects of the mine such as subsi-dence, but also to the protection against radioactive substances and the ionising radiation they emit. In order to ensure that all protection aims of the Mining, Nuclear and Water Law are complied with, a

Asse Research Mine, Remlingen

(Director: Dipl.-Ing. Günther Kappei)

S safety report will be attached to the closing down operation plan for the Asse Mine, in which evidence for the long-term safety is provided.

Since 1995 the stopes in the southern part of the Asse Research Mine dating back to the times at which rock salt was mined have been fi lled up with indigenous mate-rial. The Asse site and its fi lling are monitored by geotechnical, geophy-sical and hydrogeological measu-ring programmes. Parallel to this measure for stabilising the mine layout, work is also being done to ensure the long-term safety of the pit. This evidence is an essential part of the safety report to be attached to the closure operation plan.

In late November 2006, 37 scien -tifi c and technical employees, 88 other employees and 14 trainees worked at the Asse Research Mine.

The mobile construction materials

system on the 750 m level.

Gen

eral

Dev

elo

pm

ent

59 �

Inst

itute

of

Ecol

ogic

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hem

istry

Dr.

S. S

chul

te-H

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de(p

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sion

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Inst

itute

of

Soil

Ecol

ogy

Prof

. Dr.

J. C

. Mun

ch

Inst

itute

of

Gro

undw

ater

Ecol

ogy

Prof

. Dr.

R. M

ecke

nsto

ck

Inst

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of

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hem

ical

Plan

t Pat

holo

gyPr

of. D

r. J.

Dur

ner

(pro

visi

onal

)

Inst

itute

of

Toxi

colo

gy

Prof

. Dr.

M. G

öttli

cher

Inst

itute

of

Biom

athe

mat

ics

and

Biom

etry

Prof

. Dr.

R. L

asse

r

Inst

itute

of

Rad

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olog

y

PD D

r. M

. Atk

inso

n

Inst

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of

Mol

ecul

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adia

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Biol

ogy

Prof

. Dr.

J.-M

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dde

Dep

t. En

viro

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tal

Engi

neer

ing

Dr.

H. S

eidl

itz

Trai

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Cen

tre

Dr.

W. K

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nger

Asse

Res

earc

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Dip

l.-In

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. Kap

pei

Inst

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of

Inha

latio

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Prof

. Dr.

H. S

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z(p

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Inst

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Dev

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tal

Gen

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s

Prof

. Dr.

W. W

urst

Inst

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.Dr.

R.B

rack

-Wer

ner

(pro

visi

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)

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logy

Prof

. Dr.

Dr.

H.-

E. W

ichm

ann

Inst

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of

Bioi

nfor

mat

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Prof

. Dr.

H.-

W. M

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Inst

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of H

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san

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Vasi

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Prof

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Prof

. Dr.

H. H

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mun

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Prof

. Dr.

D. S

chen

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Prof

. Dr.

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Prof

. Dr.

Dr.

H. G

. Par

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Prof

. Dr.

J. S

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Prof

. Dr.

M. H

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Inst

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Prof

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Th. M

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Inst

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Prof

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Dep

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ahl

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epre

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� 60

GSF in Figures

HR Structure

GSF employees by areas

(scientists, technical, administrative).

Scientists

Technical staff including infrastructure

Administrative staff

1344 = 77%

244 = 14%

152 = 9%

Disciplines of the GSF scientists.

Biology/agricultural biology/biotechnology/botanyChemistry/biochemistryPhysics/biophysicsMedicineComputer sciencesMathematicsGeology/geography/geoecologyVeterinary medicineEngineering sciencesOther disciplines

38%

16%13%9%2%5%3%2%4%8%

Traineeships as of 12/2006.

Biology laboratory assistantsAnimal nursesOffice clerksIndustrial mechanicsEnergy electronics expertsRadiation protection engineersWarehousing specialistsComputer specialistsAgricultural assistants

34%16%15%13%7%6%3%3%3%

GS

F in

Fig

ure

s

61 �

GSF in Figures

Financing Structure

Total project funding: € 63.4 million,

of which:

German government institutionsForeign government institutionsGerman businessForeign businessTransnational organisationsOther external sponsors

76,1%1,0%1,0%0,5%6,3%

15,1%

Total institutional funding: € 95.6 million,

of which:

HRPhysical resourcesGrants/subsidiesCurrent investmentsBuilding/procurements > 2.5 million

53,36%22,21%3,35%14,9%6,17%

Federal governmentBavariaFederal government (third-party funds)EUOther third-party fundsOwn profits (basic financing)Own profits (third-party funds)

47,8%5,3%

25,3%2,4%9,5%1,3%8,4%

Total income: € 170.5 million,

of which:

� 62

Institute of Biochemical

Plant Pathology

Director: Prof. Dr. J. Durner (prov.) +49 - 89 / 31 87 – 34 34


Director: Prof. Dr. H.-W. Mewes – 35 80

Institute of Biomathematics and

Biometry

Director: Prof. Dr. R. Lasser – 41 59


Director: Prof. Dr. J. Ch. Munch – 40 65


Department Microbe-Plant

Interaction

Head: Prof. Dr. A. Hartmann – 4109


Department Experimental Simula-

tion of the Environment

Head: Dr. H. Seidlitz – 29 87


Genetics

Director: Prof. Dr. W. Wurst – 41 10

Department Zebrafi sh

Neurogenetics

Head: Dr. L. Bally-Cuif – 35 62


Director: Prof. Dr. Dr. H.-E. Wichmann – 41 07

Institute of Experimental Genetics

Director: Prof. Dr. M. Hrabé de Angelis – 35 02

Institute of Health Economics and

Health Care Management

Director: Prof. Dr. R. Leidl – 41 68

Institute of Groundwater Ecology

Director: Prof. Dr. R. Meckenstock – 25 61


Director: Prof. Dr. Th. Meitinger – 32 16


Director: Prof. Dr. J. H. Schulz (prov.) – 30 71

Institute of Clinical Molecular

Biology and Tumor Genetics

Marchioninistraße 2581377 MünchenDirector: Prof. Dr. G. W. Bornkamm0 89 / 70 99-5 01

Department Gene Vectors

Head: Prof. Dr. W. Hammerschmidt0 89 / 70 99-5 06

Institute of Biological and

Medical Imaging

Director: Prof. Dr. Vasilis Ntziachristos – 40 33


Marchioninistraße 25, 81377 MünchenDirector: Prof. Dr. D. Schendel 0 89 / 70 99-3 01


Department Gene Expression

Head: Prof. Dr. M. Meisterernst0 89 / 70 99-2 02

Institute of Molecular Radiobiology

Director: Prof. Dr. J.-M. Buerstedde – 35 16

Institute of Molecular Virology

Director: Prof. Dr. R. Brack-Werner (prov.) – 29 23

Institute of Ecological Chemistry

Director: Dr. S. Schulte-Hostede (prov.) 0 89 / 31 87 – 40 47


Director: Prof. Dr. H. Höfl er – 23 12

Institute of Stem Cell Research

Director: Prof. Dr. M. Götz0 89 / 31 87-0

Institute of Radiobiology

Director: PD Dr. M. Atkinson – 29 83


Director: Prof. Dr. Dr. H. Paretzke – 40 11

Institute of Structural Biology

Director: Prof. Dr. M. Sattler – 22 16


Director: Prof. Dr. M. Göttlicher – 27 58

Department Comparative Medicine

Head: Prof. Dr. J. Schmidt – 26 35

Asse Research Mine

38319 RemlingenLeiter: Dipl.-Ing. G. Kappei0 53 36 / 89-2 19

As of September 2007

Scientifi c Institutes and Departments

Addresses

Ad

dre

sses

/ P

ub

licat

ion

s

63 �

Information:

GSF in brief

GSF-Annual Report 2006

To Improve Human Health

From Bench to Bedside, Translational Medicine at the GSF

From the series mensch+umwelt spezial (German):

Issue 10 Schicksal aus den Genen?

Issue 11 Böden – verletzliches Fundament

Issue 12 Krank durch die Umwelt

Issue 13 Strahlende Fracht

Issue 14 Nahrungsmittel zwischen Natur und Retorte

Issue 15 Asthma und Allergien

Issue 16 Was verraten unsere Gene?

Issue 17 Grüne Gentechnik in Forschung und Anwendung

Issue 18 Strahlung – Von Röntgen bis Tschernobyl

Orders should be addressed to:

GSF-Forschungszentrum für Umwelt und GesundheitAbteilung KommunikationPostfach 112985758 Neuherberg, Germany

GSF-Forschungszentrum für Umwelt und Gesundheit

Ingolstädter Landstraße 185764 NeuherbergTelephone: +49 - 89 / 31 87-0Telefax: +49 - 89 / 31 87-33 24Internet: www.gsf.dee-mail: [email protected]

You Can Obtain the Following Material From the GSF:

Publications

� 64

HaltestelleFeldmochingU2/U8

S 1

S 8

S 1

* The Haematologikum of the GSF can be reached by the U6 underground from Marienplatz to Großhadern (approx. 30 minutes).

Map

MUNICH AIRPORT

*

Annual Report 2006 - Helmholtz Zentrum München · 2007-10-18 · Following Radiation Exposure ......

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