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To Improve Human Health

The GSF – National Research Centerfor Environment and Health

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GSF – National Research Center forEnvironment and HealthMember of the Helmholtz Association of German Research CentresIngolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 0Fax: +49(0)89/3187 3324www.gsf.de

© GSF 2007

Editors

Cordula Klemm, Michael van den Heuvel, Heinz-Jörg Haury

Distribution and Editorial Assistance

Monika Wiedemann, Brigitte Schmid,Communications [email protected]

Photographs by

Prof. Dr. Jerzy Adamski, Ulla Baumgart,Prof. Dr. Heidrun Behrendt, Evi Bieber,Nick Bougrov, CDC, Prof. Dr. FriederikeEckardt-Schupp, FOTAG Luftbild, Prof. Dr. Magdalena Götz, GSF-Archiv, Dr. Ulrich Heinzmann, André Künzelmann,Bernd Müller, Photocase, Prof. Dr. PeterSchröder, Marc Schwientek, AndreasStampfl, Michael van den Heuvel, Dr. Klaus Wittmaack, Helga Wehnes,Verband der forschenden Arzneimittel-hersteller/Amgen. All other photos anddiagrams by GSF – National ResearchCenter for Environment and Health

Layout

Büro 31 – Visuelle Kommunikation und Fotografie, Augsburgwww.buero31.de

Printing

Senser Druck GmbH, Augsburg

3

Preface

Over the last year the GSF, a member of the Helmholtz Associ-ation, has initiated to significantlystrengthen its research efforts in environmental diseases. Thisstrategic choice was made for tworeasons: the huge global medicalneed and economic burden as wellas our unique research capabilitiesto address such grand challenges.Under one roof the GSF combinescritical mass and competence inthe fields of health research as wellas ecosystem analysis for soils,plants and ground water. This com-bination enables us to link aspectsof health and environment andopen new avenues of insight intomechanisms of health and dis-eases. We are currently strength-ening and extending our capabil-ities in translational medicine withour clinical partners. It is our ambi-tion to contribute to the foundation

of future medicine in terms of prevention, diagnostics and causalindividualized therapy, as well as the preservation of ecosystem services.We are also highly committed tooffer excellent opportunities fortraining and education as well asattractive career opportunities.With this brochure we would liketo give an overview of our insti-tutes and departments and theirareas of research. We do hope that this compilation will stimulateto think about common areas ofinterest and open chances for newcollaborations and partnerships.

Günther Wess Nikolaus Blum

Prof. Dr. Günther Wess,

Chief Executive Officer

Dr. Nikolaus Blum,

Chief Operating Officer

4

Contents

Preface 3

Contents 4

To Improve Human Health 5

The Concept and the Institutes in their Thematic Fields

Environmental Factors and Health 6

Mechanistic Principles of Health and Disease 15

Infection and Immunity 27

Ecosystems and Health 33

From Bench to Bedside to Bench 40

Clinical Cooperation Groups are Committed to Translational Research

Together for the Environment and Health 50

Integration in National and International Networks and Platforms

At the Service of Research and the Public 52

Internal and External Service Facilities

Perspectives for Young Scientists 54

PhD Programme and Junior Research Groups

How Ideas are Turned into Products 58

Patents and Technology TransferLife Science Foundation and Ascenion GmbH 59

To Improve Human HealthThe Concept and the Institutes in their Thematic Fields

The GSF contributes to the foun-dations of Future Medicine and

Health Care as well as Ecosys-

tems which are of critical impor-tance for health. Our focus is onchronic degenerative diseases likelung diseases, allergies, cancer,and cardiovascular diseases thatare influenced to a large extent byenvironmental conditions, personalrisk factors, and life style.

Therefore, in order to generate aknowledge base, we analyse interactions between genetic dis-position, biological systems, andenvironmental factors. This willlead to the development of newpersonalised approaches in pre-vention, diagnostics, and causaltherapy – the future direction ofmedicine. Our strategy is based on translational approaches thatlink basic research with clinicalapplication to provide an immedi-ate benefit to the patient.

The research projects of the

GSF are focussed on four com-

plementary thematic fields:

■ Environmental Factors and

Health

■ Mechanistic principles of

Health and Disease

■ Infection and Immunity

■ Ecosystems and Health.

The GSF links the fields of biomed-icine and environmental research,relying on excellent basic research,international experimental plat-forms, clinical cooperation groups,and centres for translational medi-cine. Networking across disciplinesfacilitates exchange of knowledgeand value added creation. In addi-tion, GSF scientists ensure thatthe most recent research resultscan be incorporated in guidelinesand new legislation by participatingin national and international advi-sory commissions. As the nationalcentre of competence, the GSF

carries out important tasks withinthe field of radiation research andradiation protection. The GSF ishighly committed to scientific andtechnical excellence in its insti-tutes and departments, as well asthe promotion of young scientists.

Studying mechanisms responsible

for the specification of the different

neuronal subtypes is a promising

approach to the reconstitution of

cells in the adult nervous system.

5

6

Fascinating

nanostructures:

Brochosomes

are bioaerosols

derived from

small insects.

Unexpected

amounts of them

can be found in

the air-borne

load of ultrafine

particles.

The thematic field Environmental

Factors and Health investigatesthe mechanisms of action of che-mical and physical environmentalfactors as well as the defense andcompensatory mechanisms of theorganism. Future research willfocus, among other topics, on radi-ation and chemicals that have animpact on tumor development anda role in anti-cancer therapy on thebasis of the susceptibility of theindividual. A second focus will aimat understanding mechanisms ofinflammatory, obstructive and allergic lung diseases under theinfluence of environmental compo-nents and air pollutants. Researchon the consequences of air pollu-tion will include diseases of thecardiovascular system.

Research within the thematic field Environmental Factors and

Health is carried out by the following Institutes

■ Epidemiology

■ Health Economics and Health

Care Management

■ Inhalation Biology

■ Molecular Radiation Biology

■ Pathology

■ Radiobiology

■ Radiation Protection

■ Toxicology

The Institute of Molecular Radia-tion Biology also contributes to the thematic field Infection and

Immunity.

Environmental Factors and Health

7

Identification of Risk Genes

Genetic epidemiology studies theinfluence of environmental and geneticfactors on complex genetic diseases.For the identification of risk genes inhumans association studies are ofdecisive significance. At the Institute ofEpidemiology new candidate genes foratopic diseases (atopic eczema) werediscovered, and known genes could beconfirmed. In the genetic analysis ofmetabolic diseases promising resultswere achieved as well. Thus, e.g., agene (MC4R) was confirmed, which isoften associated with reduced bodyweight. In addition to this a gene vari-ant could be identified which is alsoassociated with obesity. In a largeinternational study one variant in theINSIG2 (insulin) gene promoter couldbe detected and replicated.


Institute of Epidemiology

The research activities of theInstitute of Epidemiology focuson the following:

■ Environmental epidemiology ■ Epidemiology of air pollution

effects ■ Epidemiology of chronic

diseases, in particular those of the cardiovascular system

■ Genetic epidemiology ■ Molecular epidemiology ■ Epidemiology – biological

samples – genomics

The health effects of fine and ultrafine particles are investigatedunder the Helmholtz programmeon Environmental Health. Aninnovative characterisation of par-ticles was carried out in the moni-toring station established in Augs-burg in 2004. Investigations werecarried out into the short-term andlong-term effects of air pollutantson health; and the factors influenc-ing the development and course of asthma, allergic diseases, andnon-allergic diseases of the respira-tory tract. The molecular basis ofasthma and allergic diseases wasinvestigated in different populationgroups.

The main focus under the Helm-holtz programme on Cardiovascu-

lar and Metabolic Disease Re-

search was research on geneticand non-genetic determinants ofcommon chronic diseases in theframework of the KORA project.Statistical planning and evaluationof genetic epidemiological studieswas performed and the KORA-genplatform set up and made availablefor population-related genetic re-search. Genetic analyses were alsoperfomed for complex diseaseslike diabetes and metabolic syn-drome.

The Institute of Epidemiology wasfounded in 1990. The Director ofthe Institute also holds the Chair of Epidemiology at the Ludwig-Maximilians-University (LMU),Munich. On average, there were50 scientists and 30 techniciansand a number of graduate andpostgraduate students and studentassistants at the two institutes –three quarters of them supportedby grant-funded research projects(more than 54 projects in total).

Head

Prof. Dr. Dr. H.-Erich Wichmann ([email protected])

Address

GSF – Institut für EpidemiologieIngolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 4066Fax: +49(0)89/3187 4499

Further Information

http://www.gsf.de/neu/Forschung/Institute/epi_intro_en.php

Research Spotlight


Institute of Health Economics and Health Care Management

8

Research Spotlight

The Institute of Health Econom-

ics and Health Care Management

investigates ways to improve theeffectiveness and efficiency ofhealth care. Using empirical meth-ods, economic and managementissues are analysed at the level ofhealth systems and care strategiesas well as of individual institutionsand technologies. As a specialfocus, it investigates how muchhealth is gained by medical tech-nology, at what costs this is achieved, and how this informationcan be used to improve health care.

Research topics include the following:■ Health systems analysis ■ Economic evaluation ■ Health care management

The Institute participates in theHelmholtz programme on Cardio-

vascular and Metabolic Disease

Research where it contributes tothe topic Epidemiology and

Public Health. In this context theResearch Unit Health Systems

Head

Prof. Dr. Reiner Leidl ([email protected])

Address

GSF – Institut für Gesundheitsökonomieund Management im Gesundheitswesen Ingolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 4168Fax: +49(0)89/3187 3375

Further Information

http://www.gsf.de/neu/Forschung/Institute/igm_intro_en.php

Analysis investigates cost-of-ill-ness issues at the population level,its response to intervention mea-sures, and socioeconomic differ-ences in health and health care,using the KORA research platformas a basis. The Research UnitEconomic Evaluation conductseconomic assessments alongsideclinical trials or on the basis ofdecision analytical models, andalso contributes to the develop-ment of evaluation methods. TheResearch Unit Health Care Man-

agement investigates incentivestructures and management inhealth insurance, as well as waysto make economic decisions onhealth care technologies on thebasis of scientific evidence.

The Institute of Health Economicsand Health Care Management was founded in 2001. Its current staff consists of 14 scientists and7 technicians.

Economic Aspects of Health Damaging

Behaviour:

Health Care Costs of Obesity

Obesity levels are rising all over theworld. In Germany, according to themost recent Federal Health Survey(2003), meanwhile 20 percent of allwomen and 17 percent of all men aged18 ore more are obese (BMI > 30).Based on data from the KORA HealthSurvey 1999/2001, we have estimatedand compared the health care costs ofGerman adults aged 25-74 years in different BMI groups. While normalweight and overweight people did notdiffer in their costs, health care costsfor those with moderate obesity (30_< BMI < 35) were 1.3 times higher andfor those with severe obesity (BMI >_35) 2.4 times higher than for normal or overweight persons. The obesityepidemic significantly contributes tothe increasing burden of serious chronic diseases – such as diabetesand heart disease – and also placesheavy financial strains on the healthcare system. Obesity has developedinto a major public health problemwhich requires serious medical andeconomic consideration. The challengefor health policy is to identify andimplement effective and efficient pre-ventive measures against obesity andits health consequences.


Institute of Inhalation Biology

9

Elucidation of the Mechanisms of

Biological Damage Caused by

Nanoparticle Exposure

Carbonaceous nanoparticles enter lungtissues within minutes after inhalation(here shown in epithelial cells) andinduce a pro-inflammatory status inthese cells and in macrophages (upre-gulation of galectin-3 shown). Subse-quent allergen exposure results in anexaggerated allergic reaction in sensi-tized mice suggesting that asthmaticsare at special risk for nanoparticle expo-sure. After just one-hour of inhalationmetal nanoparticles (chain aggregatesof 2-5 nm primary iridium particles)enter blood circulation from the lungepithelium and accumulate in second-ary target organs such as the brain,heart and kidneys during the next fewdays.

In view of gene-environment inter-actions research the Institute of

Inhalation Biology focuses onhealth risks associated with expo-sure to airborne stressors and theirpotential role in lung diseases. Inparticular, the relevance of com-bustion-derived ultrafine particles(< 0.1 µm diameter) and manu-factured nanomaterials are majorconcerns. Our aerosol researchcovers dosimetric aspects of expo-sure, but also the use of particlesfor the early detection of lung dis-ease. The DFG project Nanohaleevaluates the potential of nano-materials for targeted delivery ofpharmaceutical agents into pathol-ogically altered regions of the lungs.Our research is an integral part ofthe GSF Focus Network Aerosolsand Health. The integrated conceptof this network comprises the characterization of environmentalaerosols and the effects on humanhealth applying epidemiological andtoxicological approaches.

Research at the Institute is integrat-ed into the Helmholtz Programmeon Environmental Health with afocus on the programme topicsRedox Balance and Inflammatory

Reactions and Aerosols. Epidem-iological and toxicological studies

have shown that environmentalparticulate matter poses a healthrisk to the entire population. Indus-trial progress has clearly reducedcombustion-associated emissionsof total mass, but at the cost ofincreased emissions of ultrafineparticles and thus of total particlenumber. The exponentially growingcapabilities of nanotechnology willresult in the ubiquitous presenceof nanoparticles in our environ-ment, albeit in low concentrations.Particles within this size rangehave the capability to enter our vitalorgans, so that reasons for healthconcerns are given. In order toassess potential health risks ofultrafine and nanoparticles, particledosimetry in the developing andthe adult lung (NIH-funded), distur-bances in homeostasis and theinduction of defense mechanismsat the molecular, cellular, andsystemic levels are studied andsusceptible populations – whetheras a result of genetic predisposi-tion or of existing disease of therespiratory or cardiovascularsystems – are identified withinhuman populations and animalmodels (see also our ClinicalCooperation Group InflammatoryLung Diseases).

Head

Prof. Dr. Holger Schulz (acting)([email protected])

Address

GSF – Institut für Inhalationsbiologie Ingolstädter Landstraße 1D-85764 Neuherberg Tel.: +49(0)89/3187 4119Fax: +49(0)89/3187 2400

Further Information

http://www.gsf.de/neu/Forschung/Institute/ihb_intro_en.php

Research Spotlight

The Institute of Inhalation Biologyhas existed since 1994. The re-search programme comprises 2 core budget projects and 9 grant-funded projects with a total of 14 scientists, 16 technicians, and 2 visiting scientists.


Institute of Molecular Radiation Biology

Research at the Institute of Mole-

cular Radiation Biology aims tounderstand how ionizing radiationcauses cell toxicity, genetic disease,and cancer. It is assumed that mostof the biologically relevant effectsof radiation are related to directDNA damage in the form of double-strand breaks and oxidised bases.These lesions can lead to celldeath due to replication blockage,chromosomal missegregation, orapoptosis. Genome modificationsof surviving cells in the form ofgene deletions, base substitutions,and chromosomal rearrangementsare equally important results ofionizing radiation, as they are re-sponsible for the increased risks ofcancer and hereditary diseasesafter exposure. A variety of path-ways participate in the repair ofradiation damage, most prominentamong them being double-strandbreak repair and the excision ofoxidised bases. Many of the radia-tion-sensitive DNA repair deficien-cies manifest themselves as im-

munodeficiencies, because thedevelopment of the antigen genereceptor repertoire requires dou-ble-strand break repair factors and,at least in some vertebrate spe-cies, homologous recombination.The close connection betweenDNA damage, general DNA repair,and development of cancer meansthat current research in molecularradiobiology benefits from an openinterdisciplinary approach.

The research groups Cytogeneticsand DNA-Recombination participa-te in the Helmholtz ProgrammeEnvironmental Health and theresearch group DNA-Recombina-tion in the Helmholtz ProgrammeInfection and Immunity.

The Institute of Molecular Radia-tion Biology was founded 2002.There are 8 scientists, 2 technici-ans, and 8 undergraduate and post-graduate students working at theInstitute, approximately half ofthem supported by grants.

Chicken Cell Line Can Replace Animal

Tests

Principally the function of many genescan be studied in cell culture experi-ments rather than in animal tests. Atthe Institute of Molecular RadiationBiology the chicken cell line DT40 wasestablished as a genetic model system,in which the gene knockouts are veryeasy to carry out. Thus DT40 offers analternative for knockout experiments inanimals, so that the number of animalsused in animal tests can be reduced.For the establishment of this cell line,Prof. Jean-Marie Buerstedde wasawarded the Felix Wankel Animal Pro-tection Research Prize 2004 which isawarded for work aimed at replacingor restricting tests on living animals.

Head

Prof. Dr. Jean-Marie Buerstedde([email protected])

Address

GSF – Institut für MolekulareStrahlenbiologieIngolstädter Landstraße 1D-85764 Neuherberg Tel.: +49(0)89/3187 2871Fax: +49(0)89/3187 4093

Further Information

http://www.gsf.de/neu/Forschung/Institute/ims_intro_en.php

Research Spotlight

10

11

Mouse Model for Osteosarcoma:

Tumor Suppressor Gene Identical in

Mice and Men

Using a mouse model for osteosarco-ma it could be shown that there aremolecular genetics changes in oste-osarcoma mice, which are also rele-vant to the development of tumors inhumans. The comparison with thehuman genome showed an allele lossin the gene Tbx 18, which had onlybeen known as a development proto-col gene, in osteosarcomas in bothmice and humans. Tbx 18 is on agenome section conserved betweenmouse and man and is apparently ofgreat importance in tumor develop-ment as a tumor suppressor gene.


Institute of Pathology

The primary focus of the Institute

of Pathology is on basic and trans-lational cancer research, where we participate in the programmeson Cancer and Environmental

Health. In the Cancer Research

programme, our efforts are direct-ed at improving the diagnosis andtreatment of cancer. Here we arein the unique position of being ableto link a programme of basic re-search on animal models of cancerwith clinical studies conducted inconjunction with our partner Insti-tute of Pathology at the TechnicalUniversity of Munich. In the Helmholtz Environmental Health

programme, we draw on our expe-rience in cancer genetics and radia-tion biology to focus on definingindividual susceptibility to radiation-induced cancer. In addition to theresearch programme, the Institutemaintains pathology-based corefacilities for the GSF and for exter-nal partners, including small-animalhistopathology and biomedical imaging.

Research at the Institute focuseson the genetics of cancer. Diag-nostic/prognostic applications ofmolecular genetics are a centraltopic in the GSF Cancer Research

programme, while individual ge-netic susceptibility to radiation-induced cancer is a central topic in the Helmholtz programme onEnvironmental Health. The Institute also offers a range of services for GSF and externalpartners in the fields of biomedicalimaging (LSM, TEM, SEM) andsmall animal histopathology.

The Institute of Pathology wasfounded in 1967. At present, thestaff of the Institute comprises 4 scientists with permanent posi-tions, 6 technicians and 2 post-graduate students. The serviceactivities of the institute are per-formed by 2 scientists with per-manent positions, 3 engineers and2 technicians. In addition 3.5 scien-tists and engineers, 5 technicians,and 2 postgraduate students arefunded by grants.

Head

Prof. Dr. Heinz Höfler([email protected])

Address

GSF – Institut für PathologieIngolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 2312Fax: +49(0)89/3187 3360

Further Information

http://www.gsf.de/neu/Forschung/Institute/path_intro_en.php

Research Spotlight

12

Causes of Individual Susceptibility to

Radiation:

DNA Repair and Other Mechanisms of

Cellular Response to Radiation

The susceptibility of yeast and mam-malian cells to radiation is influencedby their repair capacities for radiation-induced DNA damages such as double-strand breaks. However, radiosensi-tivity can also be determined by otherfactors, for instance a disturbed regu-lation of cell-cycle control and of cell-death mechanisms. The radiosensitivity of NBS cells de-rived from patients with the heriditaryNijmegen Breakage Syndrome is de-termined by an enhanced frequency ofradiation-induced programmed celldeath (apoptosis) and possibly bydefects in cell-cycle progression. Theindividual sensitivity of patients toradiation can, therefore, not be predic-ted using just one single parameter,but – apart from DNA repair – othercellular functions relevant for re-sponses to radiation have to be testedas well.


Institute of Radiobiology

The Institute of Radiobiology hasa long tradition in research on ef-fects of ionizing radiation on themolecular, cellular and tissue levels.By combining approaches frommolecular biology, cytogeneticsand cell biology with genome-widescreening techniques we gain in-sight into the network of cellular

responses to radiation. The resultswill be used to estimate the individ-ual radiation sensitivity of patientsin order to allow optimized radio-therapy. Furthermore, dynamicmagnetic resonance imaging willpromote the non-invasive diagnosisof solid tumors in animal models.The institute has made importantcontributions to radioepidemiologicresearch, which serve as a basisfor the risk assessment of low-dose radiation and which haveimplications for the radioprotectionof the general population and radia-tion-exposed workers as well asfor clinical application in diagnosisand therapy. The studies are ofgreat value for society and oecon-omy, since, due to changes in life-style, exposure of the populationto ionizing and non-ionizing radia-tion is steadily increasing.

The Institute is responsible foroperating the Isotope Facility as atechnical support and service unit.The Research Group DNA Repaircontributes to the topic Responses

to DNA Damage in the Helm-holtz Programme Environmental

Health. The group investigates the

induction and repair of DNA dam-age, its role in the maintenance ofgenomic instability in yeast andmammalian cells, and in decisionswhether damaged cells undergoDNA repair or cell death. The finalgoal is the identification of markersfor the inter-individual variation of radiosensitivity in patients andtumors. The Research GroupRadiation Epidemiology contributesto the topic Low Doses of Radia-tion in the Helmholtz ProgrammeEnvironmental Health. Dynamicmagnetic resonance imaging (MRI)of angiogenesis and hypoxia intumors of animal models aims atindividualized radiotherapy. In along-term study, the somatic riskof late effects of radiation damageinduced by the incorporation of 224 Radium is analysed in MorbusBechterew patients who under-went therapy by this short-livedalpha-radiation.

The Institute of Radiobiology wasfounded in 1967. At present, thereare 9 scientists, 5 technicians, 2undergraduate and 5 PhD studentsat the institute.

Head

Prof. Dr. Friederike Eckardt-Schupp (acting)([email protected])

Address

GSF – Institut für Strahlenbiologie Ingolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 4101Fax: +49(0)89/3187 3378

Further Information

http://www.gsf.de/neu/Forschung/Institute/isb_intro_en.php

Research Spotlight

13


Institute of Radiation Protection

Research at the Institute of

Radiation Protection focuses pri-marily on applied research relatedto the measurement, evaluation,and reduction of the natural andartifical radiation exposure of thepopulation and at work places, andto the quantification of the individ-ual risk of somatic late effects dueto this type of exposure. Otherspecial research projects concen-trate on optimisation of the use ofradiation in medical diagnosticsand therapy, and the improvementof methods using ion beams formicroanalysis.

Important service functions of theInstitute include instruction, ad-vanced training, and further educa-tion in the field of radiation andenvironmental protection, and theoperation of the IAEA/WHOSecondary Standard Laboratory forDosimetry (SSDL). Provision ofexpert advice to and elaboration ofstatements for national and inter-national agencies and institutions,collaboration on the developmentof recommendations and guide-lines for radiation protection, andthe provision of information to thepublic on topical questions in radia-tion protection are another largepart of the Institute’s activities.

Development of Reference Voxel

Models for the Generation of New

Dose Conversion Coefficients

For the International Commission onRadiological Protection ICRP, whoserecommendations are usually adoptedby international (EU, UN-IAEA, OECD)and national authorities with only shortdelays, reference voxel models havebeen worked out for the highly accu-rate representation of male and femalehuman bodies in the computer. Thesemodels help generate new dose-con-version coefficients for the calculationof organ doses using given internal orexternal exposure. These computermodels were also used to carry outMonte Carlo calculations of radiationtransport. The voxel models were suc-cessfully checked for data quality andadopted by the ICRP.

Head

Prof. Dr. Herwig G. Paretzke([email protected])

Address

GSF – Institut für StrahlenschutzIngolstädter Landstraße 1 D-85764 NeuherbergTel.: +49(0)89/3187 4011Fax: +49(0)89/3187 3323

Further Information

http://www.gsf.de/neu/Forschung/Institute/iss_intro_en.php

Research at the Institute of Radia-tion Protection is carried out withinthe Helmholtz programme onEnvironmental Health in the re-search field Health.

The Institute’s Director is on theProject Board of the complemen-tary large Integrated EU ProjectRISC-RAD and on the ManagementBoard of the EU-COST project P9Principles of Radiation Interactions.The Institute also coordinates the Integrated EU Project SouthernUrals Radiation Risk Research(SOUL).

Research at the Institute of Radia-tion Protection dates back to thefoundation of the GSF in 1960. Atpresent, there are 24 scientistsand 19 technicians with permanentcontracts at the Institute. There are a further 10 scientists and 4 technicians involved in both theresearch and service functions ofthe Institute supported by research,contract, or other additional fun-ding. In addition, there are a num-ber of undergraduates, postgrad-uates, junior scientists and visitingscientists at the Institute.

Research Spotlight

14

The goal of research at the Insti-

tute of Toxicology is to elucidatethe role of chemical toxicants withrespect to the development ofcomplex disease states. Manydiseases, such as cancer or failureof the cardiovascular system, inmost cases arise from a combina-tion of causes, including impactsby environmental factors, geneticdisposition and individual lifestyleand history. The significance ofchemical toxicants in the processof disease development is deter-mined by the mechanism of actionand the potency of the compound,the level of exposure, and individu-al susceptibility. Thus the Institutefocuses on examining mechanismsof toxicity, dose-response relation-ships, metabolism and toxicokinet-ics of chemical environmental con-taminants and food components.The causes of species-dependentdifferences with respect to toxicresponse and disease state arealso studied.

In addition, mechanism-based re-search on these chemicals shouldprovide a fundamental knowledgeof the signal transduction cascades

and genetically defined programmeswhose alteration leads to the de-velopment of diseases. This re-search design will result in betterstrategies for the detection, quan-tification and reduction of healthrisks. The Institute is responsiblefor the GSF share of the topicChemicals within the Helmholtzprogramme Environmental Health,apart from a small contributionfrom the Institute of EcologicalChemistry.

The Institute of Toxicology has ex-isted since 1971. The Institute has 45 members of staff, including 13 scientists, 5 postdoctoral fel-lows and 3 guest scientists. 8 grad-uate students and 17 technicians.In addition to the guests 8.5 per-sons are supported by grants.

Head

Prof. Dr. Martin Göttlicher([email protected])

Address

GSF – Institut für Toxikologie Ingolstädter Landstraße 1D-85764 Neuherberg Tel.: +49(0)89/3187 2446Fax: +49 (0)89/3187 3449

Further Information

http://www.gsf.de/neu/Forschung/Institute/toxi_intro_en.php

Research Spotlight


Institute of Toxicology

Detoxification and Transport of

Foreign Substances: an Interdiscipli-

nary Project by Toxicology, Soil

Ecology and Microbe-Plant Interactions

When herbicides are detoxified by cul-ture plants, the metabolic productsproduced are not, as was assumed,simply stored in the vacuole of the cell,but they can also be actively transport-ed and excreted. Numerous agrochem-icals with electrophilic centers, e.g.halogens or nitrogroups, are detoxifiedby conjugation with the plant's inher-ent glutathione. The metabolites pro-duced are relatively stable glutathioneconjugates and their degradation pro-ducts, which do not stay in the cytosol,but are transported into the vacuole byspecific transporters. Recent studiesshow that such glutathione-specifictransporters are also found in the plas-ma lemma. The glutathione conjugatesare not only transported through thetissue, but a certain amount is alsoreleased into the surrounding medium.

15

Mouse models are

characterized to

understand molec-

ular mechanisms

of disease and

develop new ther-

apies.

In the thematic field Mechanistic

Principles of Health and Disease

molecular mechanisms of heredi-tary diseases are elucidated andquestions related to developmentand homeostasis are answeredwith the aid of mouse models.Stem cell research also plays animportant role. Furthermore,functional modules of biologicalsystems will be identified andclarified, which can lead to mathe-matical models and the simulationof disease processes.

Institutes contributing to the the-matic field Mechanistic Principles

of Health and Disease:

■ Bioinformatics

■ Biomathematics and Biometry

■ Developmental Genetics

■ Department Zebrafish

Neurogenetics

■ Experimental Genetics

■ Department Genome

Analysis Center

■ Human Genetics

■ Medical Informatics

■ Stem Cell Research

■ Structural Biology

■ Department Comparative

Medicine

The Institute of Biomathematicsand Biometry also contributes tothe thematic field Ecosystems

and Health; the Institute ofBioinformatics carries out researchin the thematic field Ecosystems

and Health as well; research inthe Department ComparativeMedicine is also carried out in thethematic field Environmental

Factors and Health.

Mechanistic Principles of Health and Disease

Functional Genome Analysis

The Institute of Bioinformatics hasbeen involved in the functional genomeanalysis of the most varied model or-ganisms ever since it was established.Its focuses included the processing,management and interpretation of theunderlying data. Particularly worthmentioning are the annotation (assign-ment of functions to genes) of refer-ence genomes, e.g. of the mouse, ofplants (maize, Arabidopsis thaliana),fungi (Neurospora crassa) and micro-organisms (Chlamydia). The scientistsfrom the Institute are also involved inelucidating the functions of humanhereditary material.

Research Spotlight

16


Institute of Bioinformatics

Bioinformatics is developing fromthe functional analysis of individualgenes to a system-oriented ap-proach, with the focus moving towards the description of interac-tions. Bioinformatics plays a keyrole in the development of algo-rithms and tools for the analysisand interpretation of data and leadsto scientific results and discoveriesthrough the systematic applicationof methods. The systematic cal-culation of the properties of biolog-ical macromolecules allows thegeneration of secondary databasesand network resources containingderived information which are madeavailable to the scientific commu-nity through interactive consultationas well as programmes and inter-faces. The Institute of Bioinfor-

matics develops and maintains anumber of genome and genome-related databases that are used

intensively worldwide. The Insti-tute participates in the joint bio-informatics course of the MunichUniversities. The Institute’s direc-tor, Professor Mewes, holds theChair of Genome-Oriented Bio-informatics at the Technical Univer-sity, Munich. As part of the Helm-holtz programme Comparative

Genome Research in the researchfield Health, and of the BMBF-funded network BFAM (Bioinfor-matics for the Analysis of Mam-malian Genomes), the Institute focuses on the characterization offunctional modules, the manualannotation of reference genomes(mouse, plants, fungi), the develop-ment of methods for knowledgemanagement, and contributions toseveral national and internationalresearch networks for genomeanalysis (NGFN, GABI, FUGATO,PlaNet, Helmholtz Initiative andNetworking Fund).

The Institute of Bioinformatics wasfounded in 2001. In 2005, therewere 39 scientists, technicians,and Ph.D. students at the Institute,20 of them supported by thirdparty grants.

Head

Prof. Dr. Hans Werner Mewes([email protected])

Address

GSF – Institut für BioinformatikIngolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 3580Fax: +49(0) 89/3187 3585

Further Information

http://www.gsf.de/neu/Forschung/Institute/ibi_intro_en.php

17


Institute of Biomathematics and Biometry

The main research directions ofthe Institute of Biomathematics

and Biometry are:

■ Approximation theory ■ Mathematical modelling ■ Statistics ■ Harmonic analysis

The Institute performs mathemati-cal research focused on researchareas in biology, medicine and ecology. Emphasis is on mathe-matical methods and models thatare related to applications.

The Institute has one project in the Helmholtz programme onComparative Genome Research. The focus is on the developmentand analysis of mathematicalmodels, for example in the areasof somitogenesis, lateral inhibition,and gene expression. Mathemati-cal methods for the analysis oftime sequences and images aredeveloped in three projects in theprogramme on Environmental

Health.

Approaches to quorum sensingand modern compartment modelsfor questions related to biologicalsystems are also investigated.Stochastic models for rhizosphereresearch are developed and analyzed in the programme on Biogeosystems: Dynamics,

Adaptation and Adjustment.Other research areas in this pro-gramme include spatial statistics.

The Institute of Biomathematicsand Biometry was founded in1997. At present, the Institute has 23 members of staff, including 20 scientists and 3 postgraduatestudents.

Mathematical Models in the Life

Sciences – Stochastic Models and

Simulations using the Software

Package Ants In Fields

The software package Ants In Fieldsprovides a framework for the imple-mentation and visualization of stochas-tic systems and is designed especial-ly for the simulation of a particularclass of stochastic models – so-calledMarkov fields. The name Ants indicatesthe observation that even simple pat-terns of interactions on a small scalemay produce complex patterns on alarge scale. The aim is on the one handto provide software components forthe study of stochastic systems, andon the other hand to support the trans-port of scientific knowledge usinginteractive demonstration tools. Ants isused, e.g., in genome analysis and inmedical image analysis.

Head

Prof. Dr. Rupert Lasser ([email protected])

Address

GSF – Institut für Biomathematik undBiometrie Ingolstädter Landstraße 1 D-85764 NeuherbergTel.: +49-(0)89/3187 4030Fax: +49-(0)89/3187 3369

Further information

http://www.gsf.de/neu/Forschung/Institute/ibb_intro_en.php

Research Spotlight

18


Institute of Developmental Genetics


Developmental Genetics focuseson the establishment, analysis anduse of zebrafish and mice as ani-mal models for human diseases,i.e. psychiatric and neurologicaldisorders. Besides working in theframework of the German HumanGenome Project (DHGP) and theNational Genome Research Net-work (NGFN), the Institute fostersinterdisciplinary exchange withother GSF Institutes, with Max-Planck-Institutes, and with universi-ties across Germany, as well aswith many international institutes.A clinical cooperation groupMolecular Neurogenetics is affili-ated with the Institute; the groupcollaborates closely with the Max-Planck-Institute of Psychiatry inMunich in trying to understand themolecular basis of depression andanxiety-related disorders by usingappropriate animal models. Theknowledge gained will provide newtherapeutic models for clinical re-search.

Gene Trap Technology – Tracking the

Gene Functions

Mutations are an important instrumentfor the explanation of gene functions.Gene trapping is a high-performancemethod for the large-scale mutation ofgenes, in the development of whichthe GSF Institute of DevelopmentGenetics has a leading function. Ingene trapping foreign DNA sequences(the gene trap vectors) are introducedinto embryonic stem cells of mice. Thevector integrates itself in a gene andswitches it off. So-called conditionalgene trap vectors allow the mutationof genes only at particular points intime or only in particular organs. It wasonly the development of this high-per-formance method and others thatmade an ambitious European Unionproject feasible, in the framework ofwhich up to 20,000 genes are plannedto be inactivated and their functionselucidated.

Head

Prof. Dr. Wolfgang Wurst ([email protected])

Address

GSF – Institut für Entwicklungs-genetik Ingolstädter Landstraße 1 D-85764 NeuherbergTel: +49(0)89/3187 4110Fax: +49(0)89/3187 3099

Further Information

http://www.gsf.de/neu/Forschung/Institute/idg_intro_en.php

The Institute participates in theHelmholtz programme Compara-

tive Genome Research, in whichit contributes heavily to the large-scale functional analysis of genesby producing animal models usinggene trapping, gene targeting, andRNA interference (RNAi) tech-nologies. The resultant mutantphenotypes are analyzed by insti-tute members and partially in theGerman Mouse Clinic (GMC).Following the primary phenotypingthe genetic networks underlyingthe activities of the mutated genesin the organism are analyzed usingmicroarray and yeast-two-hybridstrategies as well as bioinformaticsapproaches.

The Institute of DevelopmentalGenetics was founded in 2002. At present, the Institute has 118 members of staff, including 59 scientists, of whom 16 are visit-ing scientists and 31 postgraduatestudents – 36 scientists are sup-ported by grants.

Research Spotlight

19

The zebrafish as a model for assessing

the rewarding effects of drugs of

addiction

Mood disorders, of which drug addic-tion is an example, affect millions ofpeople worldwide. The genetic compo-nents underlying these behaviorsremain poorly understood. To gain aninsight into these processes, we devel-oped behavior paradigms assessingreward in adult zebrafish. We showedthat adult zebrafish robustly respond to the psychostimulant drug D-amphet-amine, a major component of Ecstasy.Using mutants of the cholinergicsystem, we further showed that, like inmammals, cholinergic neurotransmis-sion is involved in modulating rewardin fish. Based on these results, wescreened for ENU-induced zebrafishmutants resistant to D-amphetamine.We recovered several lines which weare currently characterizing. Our resultsvalidate the zebrafish for studies onaddiction, and are likely to result in the identification of new genetic com-ponents of the addiction process.


Department Zebrafish Neurogeneticsat the Institute of Developmental Genetics

The goal of the Zebrafish Neuro-

genetics Department at the Insti-

tute of Developmental Genetics

is to unravel the mechanisms andfactors coordinating neurogenesisand neuronal specification andfunction in the vertebrate brain.The model system is the zebrafishmidbrain-hindbrain, which harborscrucial neuronal populations in-volved in social behavior control. In this model, genetic approaches(mutagenesis, transgenesis) arecombined with manipulations ofthe embryonic and adult brain toapproach the spatio-temporal con-trol of neurogenesis and neuralstem cell maintenance and itsinfluence on neuronal specificationand function.

Specifically we study the functionof new proneural or neurogenicgenes expressed within the em-bryonic and adult midbrain-hind-brain, and we investigate the de-velopment and function of rapheserotonergic neurons, which de-velop from midbrain-hindbrain pro-genitors and are involved in moodbehavior. We further approach theoutcome of neurogenesis controlby focusing on one aspect of mood,the response to drugs of addiction.

The Department participates in theHelmholtz Research ProgrammeComparative Genome Research,in which it contributes to the spe-cific topics Functional Genome

Dissection and Stem Cells.

The Zebrafish Neurogenetics De-partment is part of the IntegratedProject ZF-Models within the Euro-pean Union 6th Framework Pro-gramme, and is further supportedby a Life Science Project Grant aswell as a special grant from theICM (Institute for Brain and SpinalCord Research, France).

The Department emanated fromthe Zebrafish Neurogenetics Groupwithin the Institute of Develop-mental Genetics as a departmentin 2006. The Department has 14 members of staff, including 9 scientists, of whom 4 are post-graduate students. 5 scientists aresupported by grants.

Head

Dr. Laure Bally-Cuif([email protected])

Address

GSF – Abteilung ZebrafischneurogenetikIngolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 3562Fax: +49(0)89/3187 3099

Further Information

http://www.gsf.de/neu/Forschung/Institute/idg_intro_en.php

Research Spotlight

The German Mouse Clinic

Genetically modified (mutated) miceare particularly well suited as modelanimals and can help create a betterunderstanding of the molecular basisof human diseases. For research onmutant mice it is decisive that alleffects of the genetic modification berecorded. This is ensured at theGerman Mouse Clinic: more than 240parameters are recorded for eachmouse in standardized conditions. Theclose interdisciplinary cooperation ofexperts from various fields of mousephysiology, genetics and pathologywith clinicians is decisive for the suc-cess of this institution renownedthroughout the world, which providesthe possibility for intensive scientificexchange (www.mouseclinic.de).

Research Spotlight

20


Institute of Experimental Genetics

The Institute of Experimental

Genetics is interested in the func-tional analysis of mammalian ge-nomes. The mouse is used as amodel organism to carry out analy-ses of gene functions and eluci-date the pathogenesis of diseases.

Head

Prof. Dr. Martin Hrabé de Angelis([email protected])

Address

GSF – Institut für Experimentelle GenetikIngolstädter Landstraße 1D-85764 Neuherberg Tel.: +49(0)89/3187 3502Fax: +49(0)89/3187 3500

Further Information

http://www.gsf.de/neu/Forschung/Institute/ieg_intro_en.phphttp.//www.mouseclinic.de

Mouse mutants are generated bychemical mutagenesis (MEP,Munich ENU Project) in order todevelop new animal models forhuman diseases. In parallel with research in the genetic control ofpathophysiological processes, theInstitute is concerned with thedevelopment and establishment ofnew methods in genomics, pro-teomics, and bioinformatics. TheGenome Analysis Centre (GAC)provides a platform for the devel-opment and application of meth-ods in genome and proteome research. The GAC is a technologyplatform open to all GSF Institutes.

A phenotyping centre for mousemutants is supported by the Na-tional Genome Research Network(NGFN). The German Mouse Clinic(GMC) develops and offers large-scale standardized phenotype ana-lyses of mouse models for humangenetic diseases. This approachensures an efficient and compre-hensive analysis and diagnosis ofthe ever-growing number of modelsfor disease. The investigations arecarried out systematically on arange of mutant mouse lines. Theinterdisciplinary institution is a col-laboration of experts from the GSF

together with research groupsfrom all over Germany. The insti-tute is also a partner in and leaderof the European Mouse MutantArchive (EMMA). The research-focus is on mechanisms of boneand cartilage diseases and theDelta Notch Pathway.

Research is carried out under theHelmholtz research programme onComparative Genome Research

in the research field Health. Theinstitute’s director is the coordina-tor of the Comparative Genome

Research programme. Its researchis concerned with the elucidation of gene functions by developingmouse models for hereditaryhuman diseases. The Institute ofExperimental Genetics collaborateswith the Helmholtz programmeson Infection and Immunity andEnvironmental Health within theresearch field Health.

The Institute of ExperimentalGenetics was founded in 2000. Ithas 91 members of staff, including35 scientists (the great majority of them grant funded), 13 visitingscientists, and 13 postgraduatestudents.

21

Its total number of staff comprises4 scientists, 2 technicians and 2 postgraduate students. Around30 scientists from different insti-tutions work at the GAC every day.The activities at the GAC are sponsored by the GSF, NGFN, EUand BMBF and industry projects.


Department Genome Analysis Centreat the Institute of Experimental Genetics

The Genome Analysis Centre

(GAC), a department at the Insti-

tute of Experimental Genetics,was established to promote high-throughput molecular research. Itsmajor focus is to investigate geno-mic and proteomic mechanisms inthe development and progressionof common complex diseases inman. The GAC is comprised ofgroups from several institutes ofthe GSF representing various dis-ciplines on the campus.

The GAC is not a service station,but provides laboratory space,equipment and computing facili-ties. Staff of the GAC maintainsthe laboratories, equipment andtraining in specific techniques. Theexperimental work has to be per-formed by the researchers them-selves.

Following the complete sequencingof the human genome, research is now focusing on the search forthe functions of genes. The mere substitution of one single baseoften results in pathogenic genetic changes. The Genome AnalysisCentre can analyze small variationson a genomic scale as well as dis-crete variations on the single genelevel. These variations can then be

analyzed for their potential impactor attributable risk of disease. Thestudies at the GAC also includeproteomic approaches to elucidatemolecular mechanisms of disease.The GAC represents an interdis-ciplinary platform horizontally pro-viding the expertise and technolo-gy between research groups.

The Genome Analysis Centre is anadministrative unit at the GSF –Institute of Experimental Geneticsand was established in 1999 asone of three genotyping centreswithin the National Genome Re-search Network (NGFN). The aimof the GAC is to perform large-scale gene analyses and to therebycreate better possibilities for genet-ic research at the GSF Institutes.The GAC offers scientists a plat-form for the development andapplication of methods in genomeand proteome research by pro-viding laboratory space and state-of-the-art technical equipment.

Head

Prof. Dr. Jerzy Adamski([email protected]))

Address

Abteilung GenomanalysezentrumGSF – Institut für Experimentelle GenetikIngolstädter Landstraße 1D-89764 NeuherbergTel.: +49(0)89/3187 3155

Further Information

http://www.gsf.de/ieg/services/gac/start.html

Research Spotlight

Small Molecule Controls Energy

Supply

The short chain dehydrogenases/reductases (SDRs) control key metabol-ic pathways of small molecules.Disfunctions of SDR enzymes contrib-ute to the pathogenesis of metabolicsyndrome, osteoporosis and cardio-vascular disorders. They represent targets for the development of specificand safe medicines. Human DHRS6 is a previously unchar-acterized member of the SDR enzymefamily. We have identified DHRS6 sub-strate by compound library screeningas R-ß-hydroxy-butyrate dehydroge-nase. The structure of human DHRS6was determined at a resolution of 1.8Åin a complex with NAD(H) and revealsa tetrameric organization with an SDR-typical folding pattern. The propertiesdetermined for DHRS6 suggest aphysiological role in cytosolic ketonebody utilization, either as a secondarysystem for energy supply in starvationor to generate precursors for lipid andsterol synthesis.

Structure of tetrameric DHRS6

Mutation Causes Hereditary-Type

Rickets

The hereditary metabolic diseasehypophosphatemia has the effect thatphosphate is lost through the kidneysand is, therefore, missing for bone for-mation. This causes bending of thebones – typically bowleg and knock-knee – similar to what occurs with rickets due to vitamin D deficiency.Studies at the Institute of HumanGenetics showed that mutations inseveral genes with different functionseventually all result in hypophospha-temia. Only recently was a mutation on chromosome four discovered,which concerns a gene responsible forthe production of the dentin matrixprotein. This protein is mainly found inthe mineralized bone matrix and it contributes to the hardening of thebone.

Research Spotlight

22


Institute of Human Genetics


Human Genetics focuses on theidentification and functional charac-terisation of disease-associatedgenes. Gene mapping techniquesare used to search for sequencevariants in man and mouse.Research topics include phosphateregulation, mitochondrial function,cardiac rhythm and cellular signal-ling pathways related to neurode-generation.

The research activities of the Insti-tute of Human Genetics are em-bedded in the Helmholtz researchprogramme Comparative Genome

Research of the Helmholtz re-search area Health and funded byDeutsche Forschungsgemeinschaft(DFG), Bundesministerium für Bil-dung und Forschung (BMBF) andthe European Union (EU). The re-search groups at the Institute applya wide spectrum of genomics toolsranging from sequence analysis toproteomics.

The Institute of Human Geneticswas founded in 2000. It has 36 members of staff: 16 scientists,8 postgraduate students, 12 tech-nical assistants, and 16 visitingscientists.

Head

Prof. Dr. Thomas Meitinger([email protected])

Address

GSF – Institut für HumangenetikIngolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 3294Fax: +49(0)89/3187 3297

Further Information

http://www.gsf.de/neu/Forschung/Institute/ihg_intro_en.php

23

Virtual Endoscopy: Contactless

Examination Method for Lungs and

Colon

A more accurate and gentler methodfor the examination of the lungs andcolon was developed: virtual endosco-py. As opposed to classical endoscopyvirtual endoscopy is contactless – thiscan exclude the risk of perforationsand infections caused by examinationsof the lungs or the colon. The virtualjourney through the colon or the lungsis generated on the computer: thethree-dimensional endoscopic imagesare generated by complex calculationusing data obtained from the X-raycomputer and magnetic resonancetechnique PET. The virtual models canbe used for diagnosis, surgery prepara-tion and therapy control.


Institute of Medical Informatics

The aim of the Institute of Medi-

cal Informatics is to develop intel-ligent assistant systems as compo-nents of an integrated health caresystem. Research is focused on:

■ Intelligent assistant systems for complex clinical working environments (imaging diagnostics, operating theaters) for greater precision and improvement of diagnosis and therapy,

■ Systems to make medical knowledge available in everydayhealth care situations, and

■ Decentralized electronic patient files and telemedicine as a basisfor integrated health care.

The Institute of Medical Informat-ics contributes to the genomeresearch programme through thedevelopment of methods for imageand signal analysis. Research at theInstitute is carried out under theHelmholtz programme on Compar-

ative Genome Research in the

research field Health. The focus ison the development of methodsfor digital image analysis and thevisualization of 3-D images and the development of methods fortelemedicine and electronic patientfiles. In the area of comparativegenome research, these methodsare used for phenotype analysis.The Institute also collaborates withthe Helmholtz programme Envi-

ronmental Health in the researchfield Health.

The Institute of Medical Informa-tics emerged from the Institute ofMedical Informatics and HealthSystems Research in 2001. TheInstitute has 15 permanent mem-bers of staff, including 6 scientistsand 1 grant-funded member ofstaff.

Head

Prof. Dr. Karl-Hans Englmeier (acting)([email protected])

Address

GSF – Institut für Medizinische InformatikIngolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 4149Fax: +49(0)89/3187 4243

Further Information

http://www.gsf.de/neu/Forschung/Institute/imei_intro_en.php

Research Spotlight

24


Institute of Stem Cell Research

The Institute of Stem Cell Re-

search addresses the basic molec-ular and cellular mechanisms ofstem cell self-renewal and differen-tiation by using complementaryexperimental approaches withstem cells from all three germ lay-ers, neural, hematopoietic and endodermal.

Primary stem cells of adult andembryonic origin, and murine em-bryonic stem cell lines are used asmodel systems. In order to answerlong-standing questions in stemcell biology, the Institute of StemCell Research uses novel technolo-gies for in vivo and in vitro molecu-lar manipulation, such as condition-al mouse mutagenesis, chimericand mosaic analyses, a variety ofpseudotyped viral and RNAi vec-tors, as well as approaches to puri-fy and culture different types ofstem cells in combination withstate-of-the-art bioimaging tech-niques.

Research at the Institute is integrat-ed into the Helmholtz programmeon Comparative Genome Re-

search to which it contributes thework on the regulation and differ-entiation of stem cells.

Besides numerous collaborationswithin the GSF and other Helm-holtz institutions, the Institute ofStem Cell Research collaborateswith German laboratories at MaxPlanck Institutes and universities inBerlin, Bochum, Dresden, Hanno-ver, Frankfurt, Freiburg, Kiel, Leip-zig and Munich. In addition, currentinternational joint research projectsinclude groups in Europe (Austria,Belgium, Denmark, France, Italy,Spain, Switzerland and the U.K.),Australia, Canada, Japan and theUSA (e.g. Princeton and HarvardUniversity, NIH, Sloan Ketteringand Einstein College of Medicine inNew York and Gladstone in SanFrancisco).

The Institute was founded in 2004and the number of people involvedin its research increased over theyears. At the end of 2005 therewere 11 scientists, 12 postgradu-ate students, 4 visiting scientists,and 8 technicians at the Institute.

Head

Prof. Dr. Magdalena Götz([email protected])

Address

GSF – Institut für Stammzellforschung Ingolstädter Landstraße 1 D-85764 NeuherbergTel.: +49(0)89/3187 3751Fax: +49(0)89/3187 3761

Further Information

http://www.gsf.de/neu/Forschung/Institute/isf_intro_en.php

Pax6 Promotes Formation of New

Brain Cells

In the adult brain dead nerve cells canpractically not be replaced. The olfacto-ry bulb is a small section of the brain,in which new nerve cells can be form-ed after all. Studies on adult mice showed that the transcription factorPax6 is required for neurogenesis inthe olfactory bulb. In particular Pax6promotes the formation of nerve cellsusing dopamine as a messenger sub-stance. These studies first demonstrat-ed how new dopaminergic cells areformed in the brain. Since Parkinson’sis due to the dying of dopaminergicnerve cells, this newly discoveredmechanism could also be a startingpoint for new therapies.

Research Spotlight

25

Left: The three-dimensional structureof the B2 protein dimer, a broadspec-trum inhibitor of RNAi. Right: NMR spectra of the B2 dimeralone [black] and when bound to ansiRNA [red]. The spectra demonstratethat the B2 dimer binds to siRNA,which is required for its ability to in-hibit RNAi.

Research Spotlight

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Institute of Structural Biology

At the Institute of Structural

Biology we study the three-dimen-sional structure, molecular recogni-tion and dynamics of biomoleculesin solution using Nuclear MagneticResonance (NMR) spectroscopy.

The Institute of Structural Biologyis associated with the Chair for

Biomolecular NMR and theBavarian NMR Centre (BNMRZ) atthe Technical University of Munich.

Biomolecular NMR is a powerfultechnique not only for determiningthe three-dimensional structures

at atomic resolution but also forcharacterizing the interactions and

dynamics of biological macro-

molecules in solution. Advances inNMR methodology and instrumen-tation allow multi-domain proteins

Head

Prof. Dr. Michael Sattler ([email protected])

Address

GSF – Institut für StrukturbiologieIngolstädter Landstraße 1 D-85764 Neuherberg Tel.: +49(0)89/6221 387 8552 Fax: +49(0)89/6221 387-98552

Further Information

http://www.gsf.de/neu/Forschung/Institute/nmr_intro_en.php

and complexes of >100 kDa molec-ular weight to be studied. We arealso interested in employing NMRas a tool in chemical biology, forexample, for studying interactionsand the modulation of conforma-tion and/or function of proteinsupon binding to small chemicalcompounds.

Recognition of proteins, nucleicacids and small molecules formsthe molecular basis for manyimportant biological processes. Thethree-dimensional structures ofthese biomolecules provide insightinto molecular details of their bio-logical function. We are currentlystudying proteins which play im-portant roles in the regulation ofgene expression, especially in-volving RNA molecules such as in splicing and RNA interference.NMR is particular suited to studytransient and more dynamic inter-actions, as are frequently observedin the regulation of splicing. Wealso investigate conformationalchanges during signal transductionprocesses, for example, associatedwith phosphorylation.

Our goal is to gain insight intomolecular and structural details ofessential biological processes, thereby providing a framework forunderstanding and curing humandisease.

Research at the Institute of Struc-tural Biology is carried out withinthe Helmholtz programme onComparative Genome Research.The Institute was founded in 2007.

26


Department Comparative Medicine

The Department Comparative

Medicine provides state of the arthusbandry of small rodents, fishand dogs to investigators as a central service for biomedical re-search. Staying at the forefront ofthe knowledge needed to fulfil itstasks successfully, research and

development (R&D) programmesrelated to laboratory animal sci-ence and welfare (LASW) are exe-cuted. The high standards of theseservices set the ground for nationaland international platforms, such asthe German Mouse Clinic (GMC)and the European Mouse MutantArchive (EMMA). In addition, theDepartment contributes to the plan-ning, application, and implementa-tion of animal experiments accord-ing to scientific needs, animal wel-fare and to German legislation byregular consultation with users inthe Institutional Animal Care andUse Committee (IACUC).

The R&D programme In Vitro and

In Vivo Models for Spontaneous

and Induced Diseases is integrat-ed into the Helmholtz programmeEnvironmental Health and focus-es on improvements of condition-al knockout techniques in the context of oxidative stress-relatedpathogenesis. Investigations intothe pathogenesis of endogenousretroviruses of inbred strains ofmice to determine their influenceon the development of lymphomas,leukemias, and skeletal disease arealso of particular interest.

Biocontainment

and Health

Monitoring of

Rodent Colonies

To meet themicrobiologicalchallenges ofmodern-daymouse facilitiesarising from fre-quent user access and import of livemice, biocontainment is of paramountimportance. To this end, mice areincreasingly kept in individually venti-lated cage systems (IVCs/microisola-tors) and transferred to new cages inclass II laminar air flow cabinets (top).To improve the microbiological moni-toring of laboratory mice kept in IVCs,a new device was developed by theDepartment which allows the detectionof infectious agents in all cages of agiven rack. For this purpose, indicatormice, called Sentinels, are kept in spe-cial cages (BioScreen) of the IVC racks.They obtain exhaust air and dirty bed-ding from all mice of this IVC rack. Thisway infectious agents are transmittedto the Sentinels and detected duringregular health monitoring by microbio-logical analyses. This method has beenpatented and licensed (bottom).

Head

Prof. Dr. Jörg Schmidt([email protected])

Address

GSF – Abteilung Vergleichende MedizinIngolstädter Landstraße 1 D-85764 NeuherbergTel.: +49(0)89/3187 2837Fax: +49(0)89/3187 3321

Further Information

http://www.gsf.de/neu/Forschung/Institute/avm_intro_en.php

The R&D programme CryoGene isintegrated in the Helmholtz pro-gramme Comparative Genome

Research. It focuses on reproduc-tive biology and microbiology inorder to develop new and ade-quate strategies to ensure a highmicrobiological status of mice andtheir biological materials. Specialtasks are the cryopreservation ofthe mouse germ line and the provi-sion of specific-pathogen-free(SPF) mice by embryo transfer.

Additional activities in the Depart-ment include the standardization of operating procedures, qualityassurance, accounting, and theimprovement of animal husbandryin conformity with animal welfare.A special function is vocationaltraining of laboratory techniciansand animal caretakers as well asfurther education and specializationof investigators in laboratory ani-mal science.

The Department was founded in 2002. It has 4 scientists, 3 post-graduate students, 35 trainees,and 71 technicians and animalcaretakers.

Research Spotlight

27

The focus in the thematic fieldInfection and Immunity is on thedevelopment of new immune andgene therapy strategies for thetreatment of malignant tumordiseases and chronic virus infec-tions. Research is concernedprimarily with tumor diseases ofthe hematopoietic system. Theelucidation of the influence of viralgenes and tumor-associatedgenetic modifications on the pro-liferation, differentiation, and trans-formation of hematopoietic cellswill contribute substantially tounderstanding the development ofthese diseases. A further impor-tant focus in this field is the analy-sis of cellular and molecular mech-anisms of immune regulation.Based on these approaches for thespecific modulation of the immunesystem for treating tumors can be developed using in vitro studiesand animal models.

Research within the thematic fieldInfection and Immunity is carriedout in the following Institutes:

■ Clinical Molecular Biology and

Tumor Genetics

■ Molecular Immunology

■ Department Gene Expression

■ Molecular Virology

■ Department Gene Vectors

The Institute of Clinical MolecularBiology and Tumor Genetics alsocarries out research in the themat-ic fields Environmental Factors

and Health as well as Mechanis-

tic Principles of Health and

Disease.

Infection and Immunity

Human astrocytes

expressing a

green fluorescent

protein.

c-MYC overexpression renders

human B lymphocytes invisible to the

immune system

Tumor development is driven by genet-ic alterations in the cells. Although theimmune system is basically capable ofdetecting even minor genetic changes,tumor cells very successfully evaderecognition by the immune systemwith the help of immunological escapemechanisms. These mechanisms areconsidered to be adaptation mecha-nisms of the tumor that are driven byin vivo selection. Studying Burkitt´slymphoma, a highly malignant humanB-cell lymphoma, triggered by the ac-tivation of the gene c-myc, it could beshown that the immune escape pheno-menon is not solely based on in vivoselection but is also part of the c-MYC-induced proliferation programme ofthe cell. A whole programme is appar-ently activated in Burkitt´s lymphomacells which impairs antigen presenta-tion and renders the tumor invisible to the immune system. Malignant proliferation and a lack of tumor cellimmunogenicity are thus two sides ofthe same coin, i.e. non-physiological c-MYC activation. Immunotherapyapproaches which are not aware ofthis connection are destined to fail.

Research Spotlight

28


Institute of Clinical Molecular Biology and Tumor Genetics


Clinical Molecular Biology and

Tumor Genetics is concerned withthe elucidation of the signal trans-duction pathways that regulate theproliferation, survival, differentia-tion, and functional activation ofcells of the hematopoietic system,as well as with the perturbation ofthese pathways by the geneticchanges that arise in the course ofmalignant transformation. Suchgenetic changes may be caused bythe uptake of additional genetic

information by the cells (viral infec-tion), or by the reorganisation ofthe existing genetic material that is organized in chromosomes(chromosomal translocations), andcan lead to a perturbed expressionof genes involved in proliferationand survival (so-called oncogenes).

The Institute participates in theprogramme on Infection and

Immunity of the Helmholtz re-search field Health.

The Institute of Clinical MolecularBiology and Tumor Genetics was founded in 1989. There are17 scientists, 7 technicians, and 23 postgraduate students workingat the Institute.

Head

Prof. Dr. Georg W. Bornkamm ([email protected])

Address

GSF – Institut für Klinische Molekular-biologie und TumorgenetikMarchioninistraße 25D-81377 München Tel.: +49(0)89/7099 501Fax: +49(0)89/7099 500

Further Information

http://www.gsf.de/neu/Forschung/Institute/kmolbi_intro_en.php

29


Institute of Molecular Immunology

Research at the Institute of Mo-

lecular Immunology is focusedon the intersection of hematology,immunology, oncology, and trans-plantation biology. Concepts aredeveloped for modulating theimmune system by means of cellu-lar and molecular methods. Newstrategies are investigated for theimmunotherapy and gene therapyof cancer, and the treatment ofautoimmune diseases and trans-plant rejection reactions. The re-search uses both animal modelsand in vitro studies with isolatedcells from the human immune sys-tem. Clinical studies based on thesestrategies are designed and carriedout in close cooperation with med-ical faculties both in Munich andelsewhere.

The Institute participates in theHelmholtz programme Infection

and Immunity.

The Institute of Molecular Immu-nology was founded in 1998. There are 10 scientists, 8 juniorscientists, 5 of them supported byresearch grants, and 14 techni-cians (5 supported by grant funds)involved in basic and appliedimmunological research at theInstitute.

Discovery of a New Path of Immune

Activation

Tumor cells often down-regulate theexpression of the major class I histo-compatibility complex (MHC-I), so thatthey can only be recognized insuffi-ciently by cytotoxic T-cells of the adap-tive immune system. Natural killer cells (NKs) of the innate immunesystem, however, can recognize cellswith down-regulated MHC-I expressionand destroy them. In a mouse tumormodel it was shown that the elimina-tion of such down-regulated cells byNK cells results in a long-lasting, T-cell-related immunological memory. Active NK cells trigger a cascade mediated by dendritic cells and thesequential expression of various cyto-kines, which finally induces cytotoxicT-cells. Thus, a new connecting linkbetween innate and acquired immuneresponse could be revealed.

Head

Prof. Dr. Dolores Schendel ([email protected])

Address

GSF – Institut für MolekulareImmunologie Marchioninistraße 25 D-81377 München Tel.: +49(0)89/7099 301 Fax: +49(0)89/7099 300

Further Information

http://www.gsf.de/neu/Forschung/Institute/imi_intro_en.php

Research Spotlight

30

Identification of a Model Gene for

the Elucidation of Gene Activation

by Viruses

The herpes simplex protein VP16 acti-vates the early genes of the herpessimplex virus, which is a prerequisitefor efficient proliferation. A specificfunctional cellular partner for VP16 wasidentified and its gene was cloned.After the gene had been cloned, it wasfound that its product binds strongly tothe so-called mediator complex, whichis involved in the regulation of humangenes. Therefore, the newly discoveredgene product is called MED25. Thereare indications that other herpes vi-ruses also bind to the mediator com-plex through MED25 and are likely toregulate their genes that way.


Department Gene Expressionin the Institute of Molecular Immunology

Both the cell proliferation and thedifferentiation of human cells arecontrolled at the level of transcrip-tion. Deregulations in transcriptioncan cause many diseases, forexample leukemia. At the Depart-

ment Gene Expression we usebiochemical methods to investi-gate mechanisms of gene control,with a focus on transcription pro-cesses. The group were the first todescribe the class of human cofac-tors. Following this, we success-fully isolated a series of general transcription cofactors and eluci-dated their molecular function. At present, the focus is on the molec-ular dynamics in transcription net-works and chromatin, which areinvestigated in selected cellular

and viral models. We expect newgenome technologies (so-calledchromatin immunoprecipitation inmicroarrays) and improved proteinbiochemistry to provide newinsights into the mechanisms ofgene programming.

Within the Helmholtz programmeon Infection and Immunity thegroup investigates structurallyinteresting T-cell genes and activa-tors that play an important role inthe immune system or in hemato-poesis. Activation of T-cells is animmunologically relevant modelsystem.

There are 6 postgraduate students,2 postdoctoral fellows, 1 grouphead, 2 technicians, and a part-time administrator in the depart-ment.

Head

Prof. Dr. Michael Meisterernst ([email protected])

Address

GSF – Institut für MolekulareImmunologie Abteilung Genexpression GSF – Haematologikum Marchioninistraße 25D-81377 München

Further Information

http://www.gsf.de/neu/Forschung/Institute/age_intro_en.php

Research Spotlight

31

Cellular Factor Inhibits Decisive Step

in HIV Proliferation

Some human cells can suppress HIVreplication. For example, certain braincells, the astrocytes, inhibit the syn-thesis of HIV components, preventingthe production of infectious virus parti-cles. The protein RISP (Rev interactingshuttle protein) inhibits the HIV Revprotein, which is required for HIV repli-cation. This discovery may lead to thedevelopment of new HIV therapies thatuse inherent cellular mechanisms tofight HIV.


Institute of Molecular Virology

Viruses play crucial roles for thedevelopment of major human diseases. On the one hand viralinfections can directly trigger dis-eases like AIDS, which is amongthe leading causes of death in theworld. On the other hand, chronicviral infections can indirectly con-tribute to numerous other chronicdiseases and may promote harmfuleffects of environmental pollutantsand drugs.


Molecular Virology aims at under-standing mechanisms of viral per-sistence, viral replication, and thedevelopment of virus-associateddiseases in humans. This knowl-edge is exploited to develop newdiagnostic and therapeutic con-cepts. The detailed understandingof the strategies used by virusesto interact with cells and to influ-ence the immune system of thehost provides the basis for the development of viral tools for im-mune and gene therapy.

The Institute is integrated into theprogramme Infection and Immu-

nity within the Helmholtz researcharea Health, and collaborates withother Helmholtz-institutions in theareas of Pathogenesis, Micro-

organisms, and Prevention and

Therapy. In addition, the Institutemaintains active collaborative tieswith programmes on Comparative

Genome Research, Environmen-

tal Health, and Cancer Research

in the research area Health.

The Institute of Molecular Virologywas founded in 1991. At present,there are 13 scientists, 8 techni-cians, and 9 postgraduate studentsat the Institute. 12 members of the Institute are supported by addition-al funds.

Head

PD Dr. Ruth Brack-Werner (acting)([email protected])

Address

GSF – Institut für Molekulare VirologieIngolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 3004Fax: +49(0)89/3187 3329

Further Information

http://www.gsf.de/neu/Forschung/Institute/imv_intro_en.php

Research Spotlight

32

Mini EBV Vectors Activate Specific

Cytotoxic T-Cells

The Epstein-Barr virus (EBV) is associ-ated with a number of tumors whichmainly occur in immune suppressedpatients. The immunologic control ofEBV is conducted using cytotoxic T-cells almost exclusively. Mini EBV vec-tors developed at the Department ofGene Vectors are effective tools for thegeneration of not only virus-, but alsotumor-antigen-specific T-cells in vitro:mini EBVs are “stripped” viruses com-prising only nearly half of the heredi-tary substance of the wild type. Due totheir smaller genome they can take innew information – e.g. DNA sequencescoding for tumor antigenes. When apatient’s B-cells are infected with suchmini EBVs, they will be immortalizedon the one hand – i.e. the cell line cangrow infinitely – and on the other handthey produce virus antigens or the de-sired tumor antigen. This way antigen-specific T-cells can be activated for theimmune therapy of tumors.


Department Gene Vectors

Research in the Department Gene

Vectors is concerned with themolecular analysis of a human her-pes virus, the Epstein-Barr virus(EBV), and the interaction of thevirus with its host cell. The molec-ular research focuses on differentaspects of the control and regula-tion of cell proliferation, DNA repli-cation, and the signalling of cellularand viral receptor molecules. Wehave developed tools that allowthe targeted manipulation of thepathogenic characteristics of thevirus, and the construction of safegene vectors. These EBV-derivedgene vectors can deliver genes of therapeutic interest into normal ortransformed human B-cells.

The research is carried out underthe Helmholtz programme onInfection and Immunity. The cen-

tral research theme is the elucida-tion of gene functions of thehuman herpes virus, Epstein-Barr(EBV) with particular emphasis onlatent genes. The viral latent genesare involved in a stable mainte-nance of the viral genome and thedifferentiation and survival of thehost cell. As a common themeviral genes have cellular counter-parts with analogous functions,indicating that the virus can mimicimportant cellular functions. Weuse a broad spectrum of methodsand techniques from the fields ofgenomics, proteomics, bioinfor-matics, and phenotype analysis, tohelp improve the understanding ofthe basic mechanisms and devel-opment patterns of tumors in man.We collaborate with other groupswithin the Helmholtz programmeon Infection and Immunity.

The Department of Gene Vectorswas founded in 2002. Today 10 scientists, 10 postgraduate students, and 4 technicians workin the Department, two thirds ofthem are supported by externalgrants.

Head

Prof. Dr. Wolfgang Hammerschmidt([email protected])

Address

GSF – Abteilung Genvektoren Marchioninistraße 25D-81377 MünchenTel.: +49(0)89/3187 1506Fax: +49(0)89/7099 225

Further Information

http://www.gsf.de/neu/Forschung/Institute/agv_intro_en.php

Research Spotlight

33

Investigating

effects of changing

environmental

conditions on

plants helps to

maintain safe and

sufficient food

production in the

future.

The thematic field Ecosystems

and Health looks at the complexinteractions between abiotic andbiotic components in environmen-tal ecosystems and their influenceon the quality of the most impor-tant components of the human diet:plants and water. The function andactivity of organisms and microbialcommunities in their environmentswill be analyzed, and attemptsmade to reduce the application ofchemicals in agriculture by activ-ating plant immunity and microbialfunctions. This thematic field alsocontributes to the prevention ofenvironmental diseases by researchinto environmental processes thatare a prerequisite for a healthybasis for life.

Institutes contributing to the the-matic field Ecosystems and Health:

■ Biochemical Plant Pathology

■ Ecological Chemistry

■ Groundwater Ecology

■ Soil Ecology

■ Department Environmental

Engineering

■ Department Microbe-Plant

Interactions

The Institute of Ecological Chem-istry also contributes to the the-matic field Environmental Factors

and Health.

Ecosystems and Health

34


Institute of Biochemical Plant Pathology

The Institute of Biochemical

Plant Pathology focuses on theanalysis of the role of plants instressed terrestrial ecosystemsand in human nutrition.Environmental stress and infectionby pathogens leads to a networkof stress responses, depending onthe type, genotype, and develop-mental status of the plants. Thiscan lead to resistance, but may alsoresult in susceptibility and damage.The research conducted at theInstitute is based on the recognitionof the wide variety of harmful envi-ronmental factors. It helps clarifythe mechanisms and ecologicalimportance of the response tothese environmental factors at themolecular and physiological levels.

Investigations focus on the impactsof atmospheric pollutants, UV-Bradiation and pathogens with afocus on plant health. The molecu-lar mechanisms of damage andinduction of resistance by ozone,NO, pathogens and rhizobacteriaare unraveled by genomic and proteomic techniques.

The long-term goals are to under-stand the mechanisms of plantresistance or susceptibility, and to provide a basis for molecularbreeding and the utilization of natural defense mechanisms ofplants in sustained agriculture.Most importantly, securing a healthy diet and the prevention of environmental diseases are a prerequisite for human health.

Research at the Institute is integrated into the Helmholtz programme Biogeosystems:

Dynamics, Adaptation and

Adjustment within the ResearchField Earth and the Environment.

The Institute of Biochemical PlantPathology was founded in 1986. In 2004 there were 38 members ofstaff (15 scientists, 10 postgradu-ate students, and 13 technicians)at the Institute, 6 of them sup-ported by research grants, and 6 visiting scientists from abroad.Results from our studies werepublished in 14 publications.

Molecular Mechanisms of the Innate

Immunity of Plants

The model plant Arabidopsis thalianareacts to contact with bacteria by acti-vating the innate immunity: when itdetects surface molecules of gram-negative bacteria, so-called lipopoly-saccharides (LPS), the enzyme NO syn-thase is activated and nitrogen mon-oxide (NO) is released. NO coordinatesdefense measures and activates de-fense systems. This process is a well-known feature of innate immunity inanimals. In plants the molecular mech-anisms of signal forwarding with NOas a response to LPS had beenunknown.

Research Spotlight

Head

PD Dr. Jörg Durner (acting)([email protected])

Address

GSF – Institut für BiochemischePflanzenpathologie Ingolstädter Landstraße 1 D-85764 NeuherbergTel.: +49-(0)89/3187 3434Fax: +49-(0)89/3187 3383

Further Information

http://www.gsf.de/neu/Forschung/Institute/biop_intro_en.php

35


Institute of Ecological Chemistry

Research at the GSF is concernedin the broadest sense with theinteraction between the environ-ment – both natural and anthro-pogenically altered – and humanhealth. The activities of theInstitute of Ecological Chemistry

lie at the interface of these twoareas. On the one hand, researchfocuses on the presence and be-haviour of chemicals in the envi-ronment with the aim of evaluatingenvironmental changes in terms oftheir implications both for man andfor the environment itself, and for-mulating appropriate measures toaddress them. On the other hand,changes in chemicals in organisms,including man, are determined ana-lytically, and possible connectionsinvestigated with substances, bothnatural and anthropogenic, presentin the environment.

Diesel soot intensifies allergic reac-

tions – cooperation between TU

Munich and GSF

Fine and ultrafine particles from the air,which include the exhaust gases ofdiesel vehicles, may boost allergies. Itis the organic components of dieselsoot in particular – mainly polycyclicalaromatic hydrocarbons (PAH) – whichseem to aggravate allergies: togetherwith aerosol extracts containing differ-ent PAH concentrations birch pollenallergens caused a noticeably strongerallergic reaction than just the pollen –but only, if there had been an allergybefore. This effect was even foundwith PAH concentrations as they occurin the natural environment and a dose-related increase was observed –the strongest activation was seen withthe highest PAH content. Aerosolextracts alone, however, caused noallergic reaction.

Head

Dr. Sigurd Schulte-Hostede (acting)([email protected])

Address

GSF – Institut für Ökologische Chemie Ingolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 4047Fax: +49(0)89/3187 3371

Further Information

http://www.gsf.de/neu/Forschung/Institute/ioec_intro_en.php

Research at the Institute is inte-grated into two Helmholtz pro-grammes. The presence, distribu-tion and interaction of substancesin living and inanimate environmen-tal systems are investigated under the programme Biogeosystems:

Dynamics, Adaptation and Ad-

justment. The main focus underthe programme on Environmental

Health is on the analysis of thechemical charge of ultrafine parti-cles, as there are indications thatthis plays a role in the effect theseparticles have on health.

The Institute of Ecological Chem-istry was founded in 1969. At present, there are 14 scientists, 4 junior scientists, 36 visitingscientists, 15 postgraduate stu-dents, and 22 technicians at theInstitute, some supported undergrant-funded projects (sponsors:Federal Government, State ofBavaria, various foundations, indus-trial companies, EU, and DFG).

Research Spotlight

36

New Biochemical Reaction in the

Anaerobic Degradation of Polycyclical

Aromatic Hydrocarbons

Contamination with mineral oils, inparticular with aromatic hydrocarbons,jeopardizes the drinking water. Sincedissolved oxygen is consumed fast byaerobic degradation of hydrocarbons,most of the microbial degradation occurs anaerobically. The activation ofnon-substituted aromatic hydrocar-bons by methylation is a newly discov-ered biochemical reaction by which the polycyclical aromatic hydrocarbonscan be degraded in a low-oxygen envi-ronment. This discovery has, e.g.,implications for the determination ofdegradation reactions in contaminatedgroundwater aquifers.


Institute of Groundwater Ecology


Groundwater Ecology focuses onattenuation processes and thetransport of pollutants in contami-nated aquifers. Crucial parametersof groundwater systems are deter-mined, such as water flow path-ways and heterogeneity, water ori-gin, and vulnerability to pollution,using environmental isotope dataand mathematical models. A majorfocus is on the investigation of thenatural microbiological attenuationprocesses that lead to the self-sus-taining purification of groundwaterand thus to securing our mostimportant resources of drinkingwater.

The Institute participates in theHelmholtz research programme on Biogeosystems: Dynamics,

Adaptation and Adjustment

in the research field Earth and

Environment. Three researchgroups work on Topic 4.1 studyingheterogeneities in aquifers and

their impact on the transport ofgroundwater and pollutants. In addition, mixing processes be-tween groundwater and surfacewater are investigated using stableisotopes. Three research groupsthat work on Topic 4.2 have joinedthe programme. They investigatethe ecology of microorganisms ingroundwater. Parameters are iden-tified that have a significant influ-ence on the microbial degradationof pollutants in groundwater or onwater quality. In addition, new an-aerobic microorganisms are iso-lated that can degrade aromatichydrocarbons, and their metabolicpathways are elucidated.

The Institute of GroundwaterEcology evolved in 2003 from the former GSF Institute of Hydrology.10 scientists, 11 technicians, 15 junior scientists, and 12 post-graduate students work at theInstitute.

Head

PD Dr. Rainer Meckenstock([email protected])

Address

GSF – Institut für Grundwasserökologie Ingolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 2561Fax: +49(0)89/3187 3361

Further Information

http://www.gsf.de/neu/Forschung/Institute/igoe_intro_en.php

Research Spotlight

37

Discovery of Key Organisms in

Ammonium Conversion

Archaea are archaebacteria which haveso far mostly been found in very ex-treme habitats. In an international studygroup from Norway, Scotland, the USA and Germany we could identify asubgroup of these archaebacteria, so-called crenarchaeota, as key organismsin the oxidation of ammonium in soils.Ammonium is at the centre of theglobal nitrogen cycle: it is formed,when proteins and amino acids, whichenter the soil with the dead animal orplant substance, are decomposed.Ammonium oxidation is the first stepof nitrification, in which microorgan-isms use oxygen to convert ammo-nium into nitrate. It had always beenassumed that it is mainly gram-nega-tive autotrophic bacteria which areresponsible for this step in the metab-olism.

Research Spotlight


Institute of Soil Ecology

Research at the Institute of Soil

Ecology is concerned primarily withthe understanding and regulationof essential microbial functions ofsoils. Controlling these processesshould enable more sustainableuse both for plant production andecosystem services. Research atthe Institute ranges from the mo-lecular and microscale in the labo-ratory to the macroscale of a land-scape (Research Farm Scheyern).The exposure chambers and lysi-meters provide a link between thetwo. On the one hand, the bioticcomponents of the soil are charac-terized in their totality and theirperformance detected in part usingstable (15N, 13C) and radioactive (14C)isotopes. On the other, the com-position of the extremely complexmicrobial communities is deter-mined using new molecular meth-ods that have been and are being(further) developed at the Institute.The focus of research conductedat the Institute is on the elucidationof active microbial communitiesand the functions of redundancy in the functioning of terrestrial eco-systems. In terms of sustainableand environmentally acceptablesoil use, these functions are directed at the transformation ofnutrients and pollutants and the

Head

Prof. Dr.Jean Charles Munch([email protected])

Address

GSF – Institut für BodenökologieIngolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 4064, 4065Fax: +49(0)89/3187 2800

Further Information

http://www.gsf.de/neu/Forschung/Institute/iboe_intro_en.php

Bacteria Archaea

Crenarchaea

Thermoproteus

Pyrodictum

Eucarya

biocontrol of phytopathogenicmicroorganisms in the root area ofplants. Knowledge about theredundancy in microbial functionsprovides the basis for informationsystems. A broad spectrum of ana-lytical methods is used from geo-chemistry, stable isotope probing,genomics, proteomics, metabolo-mics to mathematical processmodelling. The research is carriedout under the Helmholtz researchprogramme on Biogeosystems:


Adjustment in the research fieldEarth and Environment.

The Institute’s director is deputycoordinator of the Helmholtz pro-gramme.The Institute of Soil Ecol-ogy was founded in 1987. At pre-sent, there are 21 scientists, 16postgraduate students, 8 under-graduate students, 16 technicians,and 7 trainees participating in theresearch. In addition, there are vis-iting scientists from various Euro-pean, Asian, and South Americancountries.

38


Department Environmental Engineeringin the Institute of Soil Ecology

The Department Environmental

Engineering (EUS) evolved fromthe former Exposure ChamberGroup and is formally integratedinto the Institute of Soil Ecology.In its role as a service facility, EUSperforms technical simulations ofenvironmental conditions for theinvestigation of plant-soil systems.

The EUS activities focus on thestudy of the impact of global changein various environmental factors,for example increased concentra-tions of carbon dioxide and ozone,raised levels of UV-B radiation andhigher temperatures on importantplants. The EUS provides experi-mental platforms such as exposurechambers, sun simulators, a re-search greenhouse, a facility forfield fumigation with carbon diox-ide, and a large-scale lysimeterfacility for the study of transport inthe atmosphere-plant-soil-ground-water system. These platforms

allow the study of agriculturallyrelevant biogeosystems in a realis-tic and reproducible environment.Chamber experiments and fieldstudies are often linked together inorder to validate the findings.

The Steering Committee of theMunich Biosystems Network(MABIF), which advises the GSFscientifically in the planning andevaluation of the chamber experi-ments, recommends the approvalof chamber experiments. Mostexperiments are embedded in cooperative projects with othernational and international researchgroups.

Recent chamber experiments are included in the Deutsche For-schungsgemeinschaft CollaborativeResearch Centre activity (SFB)607, which was set up in 1997,and in which the two Munich uni-versities and the GSF participatewith a number of cooperative pro-jects. The lead topic under investi-gation in SFB 607 is “growth andparasite defense? Competition forresources in agricultural and forestplants of commercial interest.”

Other experiments focus on the UV tolerance of various barley cultivars and on the competition of beech trees for nitrogen com-pounds and water.

The contribution of EUS to theHelmholtz programme Biogeo-

systems: Dynamics, Adaptation,

and Adjustment is mainly focussed in Subprogramme 4.3 Stress and Adaptation, Plants in

Changing Habitats and PSIA Soil-

Plant Interactions in Agricultural

Biogeosystems.

The Department has existed since2001, the Exposure Chambers firstwent into operation in 1984. At present, there are 6 scientistsand 16 technicians in EUS.

Head

Dr. Harald K. Seidlitz([email protected])

Address

GSF – Abteilung ExperimentelleUmweltsimulationIngolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 2431/2406Fax: +49(0)89/3187 4431

Further Information

http://www.gsf.de/neu/Forschung/Institute/eus_intro_en.php

Lysimeters are a perfect platform to

study substance transport between

the atmosphere, plants, soil, and

groundwater.


Department Microbe-Plant Interactions

Interactions between microbes andplant roots are controlled by mole-cular communication within themicrobial community colonizing theroot and between microbes andplants. The microbial colonizationof roots is of key importance forthe supply of nutrients to theplants and for plant health, as wellas in the transformation and degra-dation of natural and anthropogeniccompounds. A further focus is thepossible colonization of roots andplants by human-pathogenic andtoxin-producing bacteria. The orga-nismic interactions are studied atthe genomic, expression and meta-bolomic level with molecular gene-tic, biochemical, microbiologicaland advanced microscopic tech-niques.

The aim of the research is to usein depth knowledge of the molec-ular interplay to establish desiredbiochemical traits such as plantproductivity, disease resistance,and pollutant degradation. Further-more, health risks are evaluatedthrough the assessment of theoccurrence of human pathogenicbacteria and toxins in the roots andshoots of agricultural plants. Theexperimental work is performed inlaboratory, greenhouse and fieldstudies (Research Farm Scheyern).

Research of the Department Mi-

crobe-Plant Interactions is inte-grated into the Helmholtz researchprogramme on Biogeosystems:


Adjustment in the research fieldEarth and Environment. The aimis to elucidate mechanisms of theinteractions of the microbes colo-nizing plant roots at the surface(rhizoplane) and endophytically thatlead to improvements in plantnutrition and health and optimiza-tion of the degradation of pollu-tants in the rhizosphere.

The research is performed in col-laboration with the PhytosphereInstitute (ICG-III) of the ResearchCentre Jülich (FZJ), and the GSFInstitutes of Biochemical PlantPathology, Soil Ecology, EcologicalChemistry, Biomathematics/Bio-metry, Groundwater Ecology andToxicology. A cooperation with theGSF Institute of Molecular Immu-nology and the Clinical CooperationGroup Pediatric Immunology ad-dresses the interaction of probioticgut bacteria and their signallingmolecules with responses of thehuman immune system. The headof the Department coordinates the GSF additional funding project Molecular interactions in the rhizo-sphere.

The Department was founded in2006 and has developed from theDepartment of Rhizosphere Biologyat the Institute of Soil Ecology. Itparticipates in the Helmholtz VirtualInstitute on Biotic Interactions.

In 2006 it consists of 6 scientists,7 postgraduate and 2 undergradu-ate students, 2 technicians, 2young people doing their voluntaryecological year and 3 visiting scien-tists from Europe, Israel and India.

Head

Prof. Dr. Anton Hartmann([email protected])

Address

GSF – Abteilung Mikroben-PflanzenInteraktionen Ingolstädter Landstraße 1D-85764 NeuherbergTel.: +49(0)89/3187 4109Fax: +49(0)89/3187 3382

Further Information

http://www.gsf.de/neu/Forschung/Institute/arb_intro_en.php

Colonization of barley roots with thehuman pathogen Salmonella thyphimu-

rium on the surface but also of the rootvascular system: The images show Barley roots inocu-lated with Salmonella typhimurium

cells and incubation for 1 (A), 2 (B) and 3 (C) weeks. CLSM image after in situhybridization with the bacteria-specificprobe EUB-338-Cy5 and the Salmonella-specific probe Salm-63-Cy3. Salmonellacells appear in magenta. B and C showorthogonal views. Bar indicates 10 µm.

39

Research Spotlight

A

C

B

40

From Bench to Bedside to Bench

Clinical Cooperation Groups areCommitted to Translational Research

Basic research is performed to understand. However,basic knowledge needs further development to finally become an instrument improving our lives.Concerning progress in clinical medicine, intenseinteractions between basic scientists and physiciansare needed. Bench needs to meet bedside and bed-side needs to communicate clinical observationsback to the bench to guarantee a substantial flow ofquestions and knowledge.

To foster transition of the latest biomedical researchresults into preventive, diagnostic and therapeuticmeasures, GSF closely cooperates with both MunichMedical Schools (LMU and TUM), Max-Planck Insti-tute of Psychiatry and Asklepios Lung Clinics. Coop-eration is institutionalized by Clinical CooperationGroups (CCG) which are selected on scientific excel-lence and flexibly organized. Their work aims at validation of promising results from basic research,further development of scientific concepts and performance of initial clinical trials, thereby guidinginnovation into clinical practice. The working topics of CCGs reflect GSF’s engagement in environmentassociated and multifactorial diseases.

■ Pathogenesis of Acute

Myeloid Leukemia

■ Molecular Oncology

■ Osteosarcoma

■ Molecular Neurogenetics

■ Inflammatory Lung Diseases

■ Environmental Dermatology

and Allergology

■ Immune Regulation in

Childhood

■ Hematopoietic Cell

Transplants

■ Tumor Therapy with

Hyperthermia

■ Antigen-Specific

Immunotherapy

■ Pediatric Tumor Immunology

Platform Technologies

■ Immune Monitoring

■ GMP-Facility

41

Head of Group

Prof. Dr. med. Wolfgang Hiddemann([email protected]) Tel.: +49(0)89/7095 2550Fax: +49(0)89/7095 8875 Deputy: Professor Stefan K. Bohlander([email protected])Tel.: +49(0)89/7099 357

Address Clinical Cooperation Group

GSF – Hämatologikum, Marchioninistr. 25, D-81377 München

Address Clinical Partner

Medizinische Klinik III, KlinikumGroßhadern der Universität München,Marchioninistr. 15, D-81377 München

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/paml/paml_index_en.php

Pathogenesis of Acute Myeloid

Leukemia

The group Pathogenesis of Acute

Myeloid Leukemia aims to findout about the effects of knownfusion proteins on the normal myeloid differentiation process andcharacterize mechanisms that leadto the deregulation of the normalproliferation and differentiation pro-gramme of the earliest hemato-poietic stem cells during malignanttransformation.

Research focus is on ■ Analysis of the effects of the

CALM-AF10 fusion protein and other leukemogenic fusions on the development of leukemia using transgenic mouse models and bone marrow transplant models

■ Analyzing the cellular function of leukemia-associated oncogenes

■ Characterization of a model development for leukemic stem cells.


Prof. Dr. med. Wolfgang Hiddemann

Leukemic cell from blood of

a person suffering from acute

myeloid leukemia.

42

Molecular Oncology

Cancer cells produce specific pro-teins which differentiate themfrom healthy cells. Often patientsdo not exhibit an effective cellularimmune response against thesetumor antigens, because the tumorcells can suppress the activation of the immune system. Thus thedevelopment of new immuno-therapies is of great clinical signif-icance. One of the main aims ofthe Clinical Cooperation GroupMolecular Oncology is the gen-eration and characterization oftumor reactive immune cells foruse in adoptive cell transfer.

Research focuses on the■ Isolation and identification of

tumor-associated antigens (TAAs) using AMIDA (Autoanti-body Mediated IDentification of Antigens)

■ Validation and characterization ofTAAs in vitro and in vivo

■ Molecular characterization of theTAA EpCAM (Epithelial Cell Adhesion Molecule)

■ Generation of TAA-specific

cytotoxic T-lymphocytes (CTLs) using the EBV vector system

■ Adjuvant immunotherapy of EBV/CMV-associated diseases using antigen-specific CTLs

Head of Group

Dr. Olivier Gires([email protected])([email protected])Tel.: +49(0)89/7095 3895 Fax: +49(0)89/7095 6896


GSF – Hämatologikum, Abteilung Genvektoren, Marchioninistr. 25, D-81377 München


Klinik für Hals-, Nasen- und Ohrenheil-kunde der Universität München, Marchioninistr. 15, D-81377 München

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/mo/mo_index_en.php

Osteosarcoma

The Clinical Cooperation GroupOsteosarcoma has two majorscientific objectives 1. Identification of Tumor Sup-pressor Genes in Osteosarcoma:In a genome-wide allelic loss studyof radiation-induced osteosarcomain mice we have identified elevencandidate loci for tumor suppres-sor genes. For two of thesemouse loci we have been able toidentify two sections on chromo-somes 6q14 and 15q21 which hadnot been described in humansbefore using a synteny comparisonby mapping markers and genes in the mouse and human genomes.We could narrow down the genelocus on 6q14 to one candidategene, TBX 18. Part of the project’sobjective is the more accurate characterization of tbx18 withrespect to its potential role in thedevelopment of osteosarcoma. 2. Identification of Susceptibility Genes in Osteosarcoma:Using a genetically defined animalmodel with radiation-induced oste-osarcomas, the genes underlying a genetic predisposition can bemapped. Applying this strategy we have mapped 1 main locus and 5 secondary loci in the mouse

Dr. Olivier Gires PD Dr. Michaela Nathrath


43

genome and favor Rb1 as a candi-date gene on the main locus.Molecular genetic and functionalinvestigations have shown that thismeans that the loss of a Wt1 bind-ing focus in the Rb1 promoterresults in reduced Rb1 expression,which is genetically associatedwith an increased predisposition to osteosarcoma. The significance of this change and other changesto the individual susceptibility forhuman osteosarcoma is investi-gated in order to be able to pos-sibly identify risk patients for de-veloping osteosarcoma.

Head of Group

PD Dr. Michaela Nathrath([email protected])Tel.: +49(0)89/3068-2887 (office), -3076 (secretary), or -2077 (Hospital)Fax: +49(0)89/3068 3811


GSF – Institut für Pathologie,D-85764 Neuherberg


Kinderklinik der Technischen UniversitätMünchen, Klinikum Schwabing SKM GmbHKölner Platz 1, D-80804 München

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/osteosarkom/index_en.php

Curious neighbours: The interaction

between mice may provide clue to

neurological disorders.

Molecular Neurogenetics

Many neurological diseases(Parkinson’s, Alzheimer’s Disease)and psychiatric diseases (depres-sion, schizophrenia) result fromaltered neurotransmitter (dopami-ne, serotonin, noradrenaline, andcorticotropin) levels in the brain. To improve our understanding ofthe cause of these diseases at theClinical Cooperation Group Mole-

cular Neurogenetics, we inves-tigate the development, the survival of the neurotransmitter-releasing neurons (dopaminergic,serotonergic, noradrenergic andcorticotropic neurons), and analyzethe molecular signalling pathwaysthat follow neurotransmitter-re-ceptor interactions. Elucidation ofthese molecular interaction cas-cades and their modeling in ani-mals will lead to a better under-standing of the origin of thesediseases and eventually to thedevelopment of novel therapeuticapproaches.

Research focuses on 1. Neuronal differentiation and

survival in the ventral midbrain and hindbrain

2. Differentiation of dopaminergic and serotonergic neurons in vitro and in vivo

3. Regulation of the stress hormone system

4. The impact of these neurotrans-mitters on animal behavior

Head of Group

Prof. Dr. Wolfgang Wurst([email protected])Tel.: +49(0)89/3187 4111Fax: +49(0)89/3187 3099


GSF – Institut für Entwicklungsgenetik,D-85764 Neuherberg


Max-Planck-Institut für Psychiatrie,Kraepelinstr. 2-10, D-80804 München

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/ng/ng_index_en.php

Prof. Dr. Wolfgang Wurst


Inhaling a remedy makes treatment

easier and more comfortable.

44

Inflammatory Lung Diseases

Research in the Clinical Coopera-tion Group Inflammatory Lung

Diseases focuses on inflammatorylung diseases, in particular envi-ronmentally-related chronic obstruc-tive pulmonary disease (COPD).COPD includes both chronic ob-structive bronchitis and emphyse-ma. Diagnosis of COPD is difficult,and the disease can only be alle-viated, not cured, by the forms oftreatment currently available. Thegroup has set itself the task ofinvestigating the mechanisms ofthe pathogenesis of these inflam-matory diseases and using theresults to develop new methodsfor diagnosis and therapy. Aerosoltechniques developed by the groupand state-of-the-art molecular-biology and immunological methodsare used. The group collaborates

Potent cause of allergies:

Microscopic image of birch pollen.

closely with the Asklepios Special-ist Clinics in Munich-Gauting,Centre for Pneumology and ThoraxSurgery.

Head of the Group

Dr. Marion Frankenberger([email protected])Tel.: +49(0)89/3187 1889 Fax: +49(0)89/893 237-11


GSF – Institut für Inhalationsbiologie,D-85764 Neuherberg


Zentrum für Pneumologie undThoraxchirurgie, Asklepios-Fachkliniken,Robert-Koch-Allee 2, D-82131 Gauting

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/am/am_index_en.php

Environmental Dermatology

and Allergology

The scientific goal of the ClinicalCooperation Group Environmental

Dermatology and Allergology isthe investigation of biogenic andanthropogenic environmental fac-tors influencing the development,the triggering, and the mainte-nance of allergic diseases andeczema. Research focuses on the

1. Relevance of pollen-associated lipid mediators in the initiation and maintenance of IgE-mediat-ed allergic inflammation

2. Molecular biology of initial responses of anthropogenic and biogenic factors on epidermis and mucous membranes in atopic and healthy individuals

3. Pathomechanism of the adjuvant activity of polycyclic

Dr. Marion Frankenberger


45

Immune Regulation in Childhood

The aim of the Clinical CooperationGroup Immune Regulation in

Childhood is to investigate hownutrition, the environment andallergies are linked together. Thegroup focuses on

■ Prebiotic and probiotic substancesResults from epidemiological studies indicate that probiotic bacteria, for example Lactobacil-lus rhamnosus, can, under cer-tain circumstances, prevent the emergence of allergic eczema. We test the effects of probiotic strains and selected bacterial signal molecules on dendritic cells and the T-cell immune response.

■ Fish oil Oily fish is rich in n-3 polyun-saturated long-chain fatty acids (n-3-PUFA). There is a hypothe-sis that increased consumption of n-3-PUFA protects against allergies. We are investigating the effect of n-3-PUFA supple-ments during pregnancy on fetalimmune parameters in a double-blind randomised European-wide study (NUHEAL, Nutraceuticals

Prof. Dr. Heidrun Behrendt

Dr. Susanne Krauss-Etschmann

aromatic hydrocarbons and particles in mouse and man

4. Phenotyping of allergic reactivityin mouse and man

Head of Group

Prof. Dr. Heidrun Behrendt([email protected])([email protected])Tel.: +49(0)89/3187 3073


GSF – Forschungszentrum für Umweltund Gesundheit, D-85764 Neuherberg


Klinik und Poliklinik für Dermatologieund Allergologie der TechnischenUniversität München, ZAUM-Zentrum Allergie und Umwelt, Biedersteiner Str. 29, D-80802 München

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/uda/uda_index_en.php

for a healthier life). Neonates are followed up until the age of six years for allergies.

■ Farms Several epidemiological studies have shown that children who grow up on working farms are better protected against aller-gies. The mechanisms of this allergy protection are unclear, however. Under the framework of an ongoing European Union study (PASTURE) we examine whether regulatory molecules ofthe immune system (ILT3, ILT4 and others) are expressed dif-ferently in farmer’s children than in other children living in rural areas.

Head of group

Dr. Susanne Krauss-Etschmann ([email protected])Tel.: +49(0)89/5160 7706Fax: +49(0)89/7099 300


GSF – Institut für MolekulareImmunologie, D-81377 München


Universitätskinderklinik der LMULindwurmstr. 4, D-80337 München

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/immunreg_kind/index_en.php


München,

46

Heating the tumor may help:

The SIGMA_EYE_MR Applicator

combines hyperthermia and nuclear

magnetic resonance.

Hyperthermia in Tumor Therapy

Hyperthermia combined withsystemic chemotherapy or radio-chemotherapy is an innovativetherapeutic concept in the specia-list area of internal oncology. Thescientific objectives of the groupinclude clinical research on deephyperthermia of solid tumors, biophysical investigation of non-invasive therapy monitoring, as-sessment of temperature-inducedtissue changes, and especially bio-logical research topics in the areasof immunology and cell biology.

Research of the Clinical Coopera-tion Group Hyperthermia in

Tumor Therapy focuses on■ Clinical deep hyperthermia ■ Combined chemotherapy

studies ■ Accompanying clinical-biology

programme ■ Research in the area of

biophysical and medical technology: thermosensitive liposomes

Hematopoietic Cell Transplants

The aim of the Hematopoietic

Cell Transplants Clinical Coopera-tion Group is the treatment of leukemias and other malignanthematopoietic diseases and solidtumors with allogenic stem celltransplants and the transfusion ofimmunocompetent cells fromdonors (adoptive immunotherapy).The aim of stem cell transplanta-tion is to achieve immune toler-ance between the patient and thetransplant, which is the prerequi-site for adoptive immunotherapy.The conditions for inducing toler-ance to the transplant and the application of adoptive immuno-therapy in chimaeras is investiga-ted in dogs and then applied tohumans.

Head of Group

Prof. Dr. med. Hans-Jochem Kolb([email protected]) Tel.: +49(0)89/7095 4241Fax: +49(0)89/7095 4242


GSF – Hämatologikum, Marchioninistr. 25, D-81377 München


J. Carreras Transplantationseinheit,Medizinische Klinik III, Klinikum Großhadern, LMU München,Marchioninistr. 15, D-81377 München

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/hzt/hzt_index_en.php

Prof. Dr. med. Hans-Jochem Kolb


47

■ Research in the area of biochemistry/immunology: Hsp70 as a danger signal: cytokine function Hsp70-peptide-complex (Hsp70-PC) chaperone functionHsp 70-activated NK cells

Head of Group

Prof. Dr. Rolf D. Issels([email protected]) Tel.: +49(0)89/7095 4769Fax: +49(0)89/7095 8876


Institut für Molekulare Immunologie, GSF – HämatologikumMarchioninistr. 25, D-81377 München


Medizinische Klinik III, KlinikumGroßhadern, LMU München,Marchioninistr. 15, D-81377 München

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/tth/tth_index_en.php

Antigen-Specific Immune

Therapy

The Clinical Cooperation GroupAntigen-Specific Immune

Therapy is investigating new immunological methods for anti-gen-specific T-cell diagnosis and therapy in humans. A major goal is to establish novel strategies providing effective CD8+ T-cell responses especially in immune-compromised patients. This should be achieved by activeimmunization with particularly safevector systems or by adoptive T-cell transfer.

The focus is on the: 1. Phenotypical analysis and

isolation of antigen-reactive T-cells using MHC multimer reagents.

2. Development of culture-dependent and -independent methods for the generation of antigen-specific T-cell popula-tions with defined specificity (suitable for GMP applications).

3. Production and immunological characterization of recombinant vector viruses based on the vaccinia virus strain MVA.

Prof. Dr. Rolf D. Issels Prof. Dr. Dirk Busch

4. Evaluation of the applicability and immunogenicity of “passive”and “active” vaccination strategies in preclinical mouse models.

5. Immunity assessment for monitoring the progress and success of antigen-specific immune therapy in humans.

Head of Group

Prof. Dr. Dirk Busch([email protected]) ([email protected]) Tel.: +49(0)89/4140 6191Fax: +49(0)89/4140 4139


GSF – Institut für Molekulare Virologie,D-85764 Neuherberg


Institut für Medizinische Mikrobiologie,Immunologie und Hygiene derTechnischen Universität München,Trogerstr. 30, D-81675 München

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/vak/vak_index_en.php


48

After binding of the Epstein-Barr virus

(EBV) to CD21 expressed on the sur-

face of B cells and subsequent end-

osomal processing of viral proteins,

peptides of viral glycoproteins are

presented on MHC class II molecules

where they can be recognized by

cytotoxic CD4(+) T-cells. These glyco-

protein-specific T-cells eliminate

newly EBV-infected cells before the

cells become transformed by the

virus and before viral replication takes

place, thereby preventing the sprea-

ding of the virus and potentially

reducing the risk of tumor outgrowth

from EBV-infected B cells.

3. Identification of viral antigens forimmunotherapy of Epstein-Barr virus-associated lymphomas

4. Development of novel strategiesfor the identification of antigens recognized by CD4(+) T-cells

5. Analysis of mechanisms involved in the presentation of endogenous antigens to CD4(+) T-cells.

Dr. Uta Behrends

Pediatric Tumor Immunology

Approximately one in five hundredchildren develops cancer, and the majority of pediatric cancerpatients suffers from cancer typesthat are infrequently observed inadults. Only three of four childrenwith cancer can be cured by con-ventional treatment, calling fornovel diagnostic and therapeuticoptions. By identifying tumor-associated antigens recognized by CD4(+) T-cells, the Clinical Co-operation Group Pediatric Tumor

Immunology aims at establishingnovel approaches to diagnosis and immunotherapy of aggressivechildhood cancer types.

The research focus is on the1. Identification of tumor antigens

in common solid childhood tumors

2. Identification of minor histo-compatibility antigens for the immunotherapy of leukemia after allogenic stem cell trans-plantation

Head of Group

Dr. Uta Behrends([email protected])Tel.: +49(0)89/7099 518Fax: +49(0)89/7099 500


GSF – Institut für KlinischeMolekularbiologie und Tumorgenetik,GSF – Hämatologikum, Marchioninistraße 25, D-81377 München


Kinderklinik und Poliklinik der Technischen Universität München im Städtischen Krankenhaus München-Schwabing, Kölner Platz 1, D-80804 München

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/pt/pt_index_en.php


49

Good Manufacturing Practice

Protocols require cleanroom condi-

tions for the production of sterile

pharmaceuticals.

Immune Monitoring

The central goal of the Clinical Co-operation Group Immune Moni-

toring is to establish and apply anumber of “state of the art” im-mune monitoring processes inongoing clinical studies. The de-manding nature of such testsnecessitates their development,standardisation and validation in clinical applications under thesupervision of qualified specialists.The fast technological develop-ments result in an ongoing improve-ment of the immune monitoringprocesses and also contribute toour fundamental understanding of the cellular and molecular regulation of the human immuneresponse in vivo.

Several immune monitoring meth-ods were validated in two clinicalstudies on the Vaccination againstHIV and Smallpox with MVA Vec-tors. Other methods are currentlybeing applied in two ongoing clini-cal studies on Allogenic Tumor Cell

GMP Facility

One aim within the ClinicalCooperation Groups is the develop-ment of new therapeutic strategieson a cellular basis against viral ormalignant diseases. To translatethe results into clinically applicableprotocols, the methods have to beadapted to GMP. The provisions ofseveral laws have to be met: Theproduction of sterile pharmaceuti-cals has to be performed undercleanroom conditions, the productmust undergo sufficient qualitycontrol before approval and an adequate quality assurance systemhas to be implemented. The GSFis building a GMP facility with cleanroom and quality control toallow the transfer of research re-sults in phase I/II studies. The firstprotocols to generate dendriticcells and specific cytotoxic T-cellsare currently being established in a pre-GMP lab and will be trans-ferred to the cleanroom after itsconstruction. In parallel the meth-ods for quality control are beingestablished and validated.Head of Group

Iris Bigalke([email protected])

Address

GSF-GMP-LaborAm Klopferspitz 19, D-82152 Martinsried

Vaccines, in the process of whichthey will also be standardised andvalidated.

New technologies, e.g. for multi-parameter cell surface analysis, arebeing further developed in parallel.Methods for the analysis of viralproteins on the level of the indi-vidual cell in the absence of viral replication have already been es-tablished.

Head of Group

Prof. Dr. Dolores J. Schendel ([email protected])Tel.: +49(0)89/7099 301Fax: +49(0)89/7099 300


GSF – Institut für MolekulareImmunologie,Marchioninistraße 25, D-81377 München


GSF – Institut für Molekulare Virologie

Institut für Medizinische Mikrobiologie,Immunologie und Hygiene derTechnischen Universität München (Prof. Dr. Dirk Busch)

Labor für Tumorimmunologie, LIFE-Zentrum des Klinikums Großhadern,LMU München (Dr. Heike Pohla)

Further Information

http://www.gsf.de/neu/Forschung/Klinische_Kooperationsgruppen/immunmonitoring/index.php

Prof. Dr. Dolores J. Schendel

Iris Bigalke


Platform Technologies

50

Together for the Environment and Health

Research Networks

The GSF’s approach to researchissues requires inter-institute, inter-disciplinary co-operation – this isreflected, among other things, inthe correspondingly large-scaleresearch networks that have beenput in place with their fully com-prehensive research objectives.

Focus Network:

Aerosols and Health

The complex nature of aerosol par-ticles and their properties as wellas their interaction with humansare reflected in the aims of theFocus Network Aerosols andHealth: Aerosol characterization,dosimetry and exposure, epidemi-ological and toxicological researchon health effects and risk assess-ment. http://www.gsf.de/neu/aerosols/index_en.php

Bayerischer Forschungsverbund

Public Health

(Bavarian Public Health ResearchAssociation) Research and service associationof Bavarian universities and otherresearch establishments. http://bfv.web.med.uni-muenchen.de/

Bioinformatics for the Functional

Analysis of Mammalian

Genomes (BFAM)

BFAM aims at research on bio-informatics integration in the sys-tematical analysis of the static

and dynamic properties of mam-malian genomes, such as regula-tory effects, genotype/phenotypecorrelations, or protein/proteininteractions.http://mips.gsf.de/projects/bfam

European Conditional Mouse

Mutagenesis Programme

(EUCOMM)

EUCOMM integrates Europeanskills, efforts, resources and infra-structure to produce mutationsthroughout the mouse genomesystematically and at a highthroughput and will make a majorcontribution to the analysis of genefunction. http://www.eucomm.org/

European Mouse Mutant Archive

(EMMA)

Association between Germany,France, the UK, Sweden, Portugal,and Italy for systematic archivingof mouse mutants. http://www.emmanet.org/

The European

Mouse Mutant

Archive preserves

new mutant

mouse lines by

keeping sperm

and embryos.

51

GABI – Genome Analysis in the

Biological System of Plants

Partner project in German plantgenome research with the aim ofobtaining information about thestructure and function of importantplant genomes.http://www.gabi.de/

GEM – Centres for Genetic

Epidemiological Methods

Network of seven German centres(Berlin, Bonn, Göttingen, Kiel,Lübeck, Marburg, and Munich)with the common goal of support-ing clinical research in the perfor-mance of epidemiological studiesrelated to complex diseases. http://www2.gsf.de:6666/gem/

German Mouse Clinic (GMC)

Network with the goal to charac-terize mouse models for humandiseases to understand molecularmechanisms of human disordersand for the development of newtherapies.http://www.mouseclinic.de/

Improved Air Quality and its

Influences on Short-Term Health

Effects in Erfurt

Network with the goal to quantifythe correlation of the improvementof air quality in Erfurt and the asso-ciated health effects.

National Genome Research

Network (NGFN)

Cooperative network of scientistsfrom various disciplines with theaim of understanding the molecu-lar basis of disease and of usingthis to achieve a clear improve-ment in the diagnosis, prevention,and therapy of important diseasesin the population.http://www.ngfn.de/

Southern Urals Radiation Risk

Research (SOUL)

Radiation risk research in theSouthern Urals – investigation ofthe late effects of plutonium production for Soviet atom bombs.http://www.gsf.de/soul/

Time capsules of

the nuclear race:

Bricks can be used

as dosimeters to

reveal radiation

exposure many

decades ago.

52

At the Service of Research and the Public

Service Platforms and Facilities

The German Mouse Clinic (GMC)at the Institute of ExperimentalGenetics provides a range of re-search methods compiled centrallyin a series of laboratory modules to allow the comprehensive and standardized phenotyping of mousemutants. http://www.mouseclinic.de/

Cooperative Health Research in

the Augsburg Region (KORA) ser-ves as a platform for a broad spec-trum of individual research projectsat the GSF and among cooperationpartners and external users. http://www.gsf.de/KORA/en/

The Munich Protein Sequence

Information Centre (MIPS) at theInstitute of Bioinformatics workson the systematic functional andstructural analysis of proteins witha focus on the characterization ofmodel genomes. MIPS supportsand maintains a set of genericdatabases as well as the system-atic comparative analysis of micro-bial, fungal, and plant genomes.http://mips.gsf.de/

The interdisciplinary research pro-grammes at the GSF require scien-tific service and other large facili-ties that for reasons of efficiencyare best operated centrally. Thesefacilities can also be used by exter-nal partners under special agree-ments.

Official Personal Dosimeter

Service

The primary task of the OfficialPersonal Dosimeter Service is themonthly determination of individ-ual radiation doses as laid downunder the official regulations foroccupational exposure to radiation;around 1.3 million dosimeters areevaluated annually. http://awst.gsf.de/http://www.gsf.de/neu/awst-hh

Services in Image Analysis and

Statistics

ImStatLab at the Institute of Bio-mathematics and Biometry pro-vides consulting services in imageanalysis and statistics in the frame-work of the R&D programme ofthe GSF. Goals of ImStatLab arethe transfer of new methods inImage Analysis and Statistics aswell as the improvement of thescientific quality of empirical re-search in the GSF. http://ibb.gsf.de/~imstatlb/

The Genome Analysis Centre

(GAC) at the Institute ofExperimental Genetics serves theinvestigation of genome and prote-ome mechanisms in the develop-ment of complex diseases. http://www.gsf.de/ieg/services/gac/start.html

When developed dosimeter film darkens in proportion to the amount of radia-

tion energy received. Due to the differing amounts of filtration information can

be gained on the energy of radiation causing the dose.

53

Cells marked by fluorescent dyes can be

sorted using laser light.

The Research Farm Scheyern

Established in 1990 and leased bythe GSF since 2005 the formermonastery estate serves as a plat-form for interdisciplinary ecosystemresearch on agricultural land. http://www.gsf.de/neu/scheyern/index_en.php

The Central Anorganic Analysis

Facility at the Institute of Ecolog-ical Chemistry performs analysesof minerals, trace elements, andanions for research projects withinthe GSF and for others. http://www.gsf.de/neu/Service/ZAA/

Antibody Platform

The Service Platform for Mono-clonal Antibodies at the Institute ofMolecular Immunology developsand provides monoclonal anti-bodies of the highest quality andplays a key role in the interlinkingof activities in German genomeresearch.

Cell Sorting Facility

The Service Facility for Cell Sortingwith the MoFlo at the Institute ofMolecular Immunology providessterile high-speed cell sorting ofinfectious and genetically modifiedcells and multiparameter analyseswith the fluorescence-activated cellsorter (FACS).http://www.gsf.de/imi/zs

54

Perspectives for Young Scientists

PhD Programme

The GSF has always placed greatemphasis on the promotion andsupport of the next generation ofscientists. Only recently was acoordinated programme of supportstarted to further increase theattractiveness of our research cen-ter for qualified PhD students andprovide them with optimum work-ing conditions. The PhD studentsare offered a programme of spe-cialized institute and interdisciplin-ary meetings of high scientific quality, which facilitate the ex-change of knowledge and experi-ence between the different pro-grammes of the GSF. In addition to the scientific training, the pro-gramme supervisors also value thecommunication of knowledge inrelated areas like making scientificpresentations, the preparation of project proposals, and projectmanagement.

Getting excellent scientists to cooperate and gaining scientific know-how as well as supportingthe establishment of a networkwith the universities – this is theaim to which the GSF – NationalResearch Center for Environmentand Health, member of the Helm-holtz Association, has subscribedwith its programme for youngscientists. We give young scien-tists the opportunity to head theirown working groups, if they partic-ipate in the programme for youngscientists. Two junior researchgroups have been explicitly estab-lished for women to support youngfemale scientists.

The Scheyern monastery provides the

setting for the meetings of the partici-

pants in the postgraduate programme

which go on for several days.

Further Information

http://www.gsf.de/neu/Jobs/phd/index_en.php

55

Perspectives for Young Scientists

Junior Research Groups

a so-called Tenure Track Option –provided the funds are available: if evidence for scientific achieve-ments is provided, the heads ofthe groups may be offered perma-nent employment after about fiveyears. It is particularly for scientistswho have families to support thatthe reliable future perspectiveinstead of the usual short-termcontracts is an important reason toaccept employment.

The funds for the junior researchgroups come from various sources– some groups are financed byGSF funds or by funds from thejunior research programme of theHelmholtz Association, othergroups are supported by institu-tions like the Volkswagen Foun-dation, the BioFuture Programmeof the BMBF (Federal Ministry ofEducation and Research) or theLife Science Foundation. It is par-ticularly for GSF junior groups sup-ported by the Helmholtz JuniorGroup Programme that networkingwith the universities is top priority.

With its junior research groups theGSF offers excellent young scien-tists an important opportunity ontheir career ladder: as head of ajunior research group they can runtheir own working groups at anearly stage and engage in indepen-dent research. Both sides benefitfrom these groups: the GSF gainsexcellent scientists and scientificknow-how, while the scientistsfind a good working environmentin which they can distinguishthemselves for their future profes-sional career. As an additionalincentive some junior groups offer

PD Dr. IrmelaJeremiasMechanisms of

Apoptosis

Dr. Vigo HeissmeyerMolecular

Programmes of

T-Cell Tolerance

Dr. med. AngelaKrackhardtAdoptive T-Cell

Therapy

Dr. Dirk NiessingMotor Protein-

Dependent Trans-

location Complexes

This ensures the mutual transfer ofknowhow between the researchcenter and the universities, whilethe scientists can also be involvedin university work with all the asso-ciated rights and obligations.

Two GSF junior groups have beenannounced for the specific supportof young women explicitly. Theheads of all junior groups shouldnot only have an outstanding doc-tor's degree, but also researchexperience abroad, because get-ting excellent scientists to comeback from abroad is an importantpurpose of the establishment ofthe groups – the motto is braingain instead of brain drain.

56

The junior groups at the GSF prove that this is a successful con-cept: their heads had been doingresearch in the US, Canada andJapan, before they came here. As a next step there are plans toestablish similar groups for scien-tists who are already working atthe GSF.

Dr. DanielKrappmannSignal Processes of

the Immune System

Dr. Brigitte Forster-HeinleinMathematical

Methods in Biologi-

cal Image Analysis

Dr. Jürgen BachlMolecular

Mechanism of

Somatic Hyper-

mutation

Dr. MatthiasKieslingerRole of the EBF

Protein Family in

the Bone Develop-

ment

Dr. Reinhard KösterNeuroimaging

57


■ Adoptive T-Cell Therapy

Dr. med. Angela Krackhardt,Institute of Molecular Immunology■ Molecular programmes of

T-Cell Tolerance

Dr. Vigo Heissmeyer, Institute of Molecular Immunology ■ Motor Protein-Dependent

Translocation Complexes in

Gene Regulation and Disease

Dr. Dirk Niessing, Institute of Molecular Immunology ■ Mechanisms of Apoptosis

PD Dr. Irmela Jeremias,Department of Gene Vectors ■ The Role of the EBF Protein

Family in the Bone Development

and the Hematopoietic Stem

Cell Niche

Dr. Matthias Kieslinger, Institute of Clinical MolecularBiology and Tumor Development

Comparative Genomics for

Human Health

■ Neuroimaging

Dr. Reinhard Köster, Institute of DevelopmentalGenetics ■ Hematopoiesis

Dr. Timm Schroeder, Institute of Stem Cell Research ■ Analysis of Early Endoderm

Development in the Mouse

Dr. Heiko Lickert, Institute of Stem Cell Research ■ Adult Neurogenesis

Dr. Dieter Chichung Lie, Institute of DevelopmentalGenetics ■ Neuronal Circuit Formation

Dr. Andrea Huber Brösamle,Institute of Development Genetics

Biogeosystems: Dynamics,

Adaption and Adjustment

■ Novel Approaches with

Compound Isotope Analysis to

Characterize the

Degradation of Pesticides

and other Groundwater

Contaminants

Dr. Martin Elsner, Institute of Groundwater Ecology

Environmental Health

■ Signal Processes of the

Immune System

Dr. Daniel Krappmann, Institute of Toxicology ■ Mathematical Methods

in Biological Image Analysis

(MAMEBIA)

Dr. Brigitte Forster-Heinlein,Institute of Biomathematics andBiometry ■ Molecular Mechanism of

Somatic Hypermutation

Dr. Jürgen Bachl, Institute of Molecular Radiobiology

14 Junior Research Groups have currently been established at the GSF:

Dr. Timm SchroederHematopoiesis

Dr. Dieter Chichung LieAdult Neurogenesis

Dr. Andrea Huber BrösamleNeuronal Circuit

Formation

Dr. Martin ElsnerNovel Approaches

with Compound

Isotope Analysis

Dr. Heiko LickertAnalysis of Early

Endoderm

Development

How Ideas are Turned into Products

Patents and Technology Transfer

Spin-off and joint venture

enterprises:

■ Bavarian Nordic Research

Institute GmbH

http://www.bavarian-nordic.com/■ Biomax Informatics GmbH

http://www.biomax.de/■ Genomatix Software GmbH

http://www.genomatix.de/■ Activaero GmbH

http://www.activaero.de/■ Ingenium Pharmaceuticals AG

http://www.ingenium-ag.com/■ Isodetect GmbH

http://www.isodetect.de/■ Sirenade Pharmaceuticals AG

http://www.keyneurotek.de/start.html

■ TRION Pharma GmbH

http://www.trionpharma.de/ ■ VAECGENE GmbH

http://www.vaecgene.de/

58

Contact

Dr. Wolfgang Nagel ([email protected])Patente & TechnologietransferTel.: +49(0)89/3187 1210Fax: +49(0)89/3187 4000http://www.gsf.de/neu/Koordination/Technologietransfer/index_en.php

Patents and Technology Transfer(PTT) at GSF forms the centralinterface between scientific re-search and industry. The missionof PTT is to assist the successfulcommercialization of innovationscreated at GSF. Scientists are ad-vised on legal questions related topatents and get support in patentapplications. PTT works closelywith Ascenion GmbH, to initiatecooperation with industry andfoster contacts with existing andpotential licensees. Currently PTTmanages around 115 patent fami-lies (patents, trademarks, andothers) in Germany and abroad.

Using bacterial traps contamination

requiring clean-up can be analyzed.

BACTRAP is used by Isodetect.

Ascenion GmbH is an intellectualproperty asset management orga-nization; it works at the interfacebetween academic research andindustrial development. The organi-zation focuses on the professionalexploitation of scientific results,discoveries and technologies fromthe GSF and other life scienceresearch establishments. Further-more, Ascenion participates in thesetting up of spin-off companiesfrom the organizations with whichit works and has a direct share inthe growth and success of thesespin-offs.Ascenion is a 100% subsidiary ofthe Life Science-Stiftung zur För-derung von Wissenschaft und For-schung (Life Science Foundationfor the Promotion of Science andResearch). The non-profit founda-tion was set up jointly in 2001 bythe four Helmholtz Centres: theGSF – National Research Centerfor Environment and Health, theGerman Cancer Research Center(DKFZ), the Helmholtz Centre forInfection Research (HZI), and theMax Delbrück Center for MolecularMedicine (MDC).

Ascenion GmbH

Further Information

http://www.ascenion.dehttp://www.life-science-stiftung.de

Back cover: Research Farm Scheyern

Aerial view of the GSF main campus

Hematological center Großhadern

(pictures clockwise from left)

to improve human health the gsf – national research center ... · diagrams by gsf – national...

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