The Genome Analysis Center · single base often results in patho-genic genetic changes. The GAC can...

The Genome Analysis Centerat the GSF – National Research Center for Environment and Health

The Genome Analysis Center(GAC) represents an interdis-ciplinary platform providing theexpertise and technology trans-fer between research groups.Following the complete sequen-cing of the human genome, re-search is now focusing on the analyses of the functions of genes.The mere substitution of only asingle base often results in patho-genic genetic changes. The GACcan analyse such small variationson a genomic scale as well as dis-

crete variations on single gene level. These variations can then beanalysed towards their potentialimpact or attributable risk for di-sease. Since the human genomeconsists of a total of three billionbase pairs, the search for such minimal differences is at least asmuch of a challenge as that for thefamous needle in the haystack. Beside this, the studies at the GACinclude also proteomic approa-ches to elucidate molecular me-chanisms of disease.

The state-of-the-art technical

equipment of theGAC offers excel-

lent conditionsfor the analysis

of genes andproteins to GSF

scientists.Foto: B. Müller

2 GSF – NATIONAL RESEARCH CENTER FOR ENVIRONMENT AND HEALTH

1. Aims of the GAC

The Genome Analysis Center(GAC) is an administrative unit atthe GSF-Institute of Experimen-tal Genetics (IEG) and was estab-lished in 1999 as one of three genotyping centres within theNational Genome Research Net-work (NGFN). The aim of theGAC is to perform large-scalegene analyses and to therebycreate better possibilities forfunctional genetic research atthe GSF institutes. The GAC of-fers to scientists a platform for

the development and applicationof methods in genome and pro-teome research by providing la-boratory space and state-of-the-art technical equipment. The re-search is performed by groups ofdifferent GSF institutions usingthe GAC. These groups provideexpertise and support throughcooperations not only at thecampus but also on a nationaland international level.

Gene Analysis as Piece-Work

In every population the genome,total genetic content, as a whole

3T H E G E N O M E A N A LY S I S C E N T E R ( G A C )

Thousands ofsamples mustbe examined to identify raregenetic varia-tions.Foto: B. Müller

differs slightly from person toperson. These differences arecalled polymorphisms. On avera-ge there is a polymorphism eve-ry approx. 300 bases with a mi-nor allele frequency of morethan 1%. Polymorphisms, whichare manifested in the variation of

just one base, are called singlenucleotide polymorphisms orSNPs. The focus of the geneticanalyses performed at the GACis on studying such SNPs using abundle of technologies such asMALDI-TOF MS (matrix assistedlaser desorption / ionisation timeof flight mass spectrometry) andarray approaches (AffymetrixGeneChip arrays). Apart fromthe SNP analyses, DNA sequen-cing and RNA expression studiesand the proteome analyses arecarried out as well.The main purpose of these inve-stigations is the identification ofgenetic differences that are in-volved in the aetiology of nume-rous wide-spread diseases suchas diabetes, neurological disor-ders, cancer as well as environ-ment-related health disordersand cardiovascular diseases. Forthese studies thousands of dise-ased and healthy control sam-ples have to be compared. Thiswould not be possible withoutstate-of-the-art analysis techno-logies, as it is available at theGAC with its high-throughputgenotyping platform.

DNA Analysis at the GAC

With the ultra-high-throughputtechniques (Sequenom, Affyme-trix) several millions of genoty-pes can be determined everyday. This makes the GAC one of

Pipetting robotsallow high

throughput sam-ple preparation.

Foto: B. Müller



Device Application Manufacturer

Robot Pipetting of reaction mixtures, of dilutions TECAN (3x),and for the purification of DNA and RNA, Beckman (4x)96- and 384-well plates

PCR devices Amplification of DNA, MJ Research (30x)sequencing reactions, Stratagene (8x),96- or 384-well plates Perkin-Elmer (2x)

Sequencing devices DNA sequencing, Beckman (8-capillary array)DNA fragment analyses ABI (16-capillary array)

ABI (48-capillary array)Microarray Spotter Transfer of DNA from PCR plates to glass BioRobotics

microchips or membranesAffymetrix Station Expression analyses of RNA and SNP Affymetrix

genotyping on chipsMALDI-TOF DNA genotyping Bruker/Sequenom(matrix assisted laser desorption/ionisationtime of flight mass spectrometer)

FPLC/HPLC (high Separation of proteins and peptides PerSeptive, Waters,

performance liquid Pharmacia Amersham

chromatography)Free flow Separation of peptides and proteins Becton Dickinsonelectrophoresis2D gel Fractionation of protein mixtures Pharmacia Amersham,electrophoresis and analysis of 2D gels BioRadQ-TOF tandem Protein identification and sequencing Micromass (Waters)mass spectrometerSELDI (surface Analysis of proteins and their interactions Ciphergenenhanced laser desorption/ionisation)Surface plasmon Interaction kinetics (protein-protein, Biacoreresonance (SPR) protein-DNA, protein-ligand) Fluoroimager Analysis of radioactive and FujiBAS 2000 fluorescence signals

2. Overview of the technical equipment of the GAC

the most powerful genotypingsites in Germany. Apart from this, DNA sequencingand fragment analyses with mi-crosatellite markers can be car-ried out at the GAC. Microsatelli-tes are a special class of poly-morphisms distributed throug-hout the genome, which are cha-

racterized by repetitions of shortDNA sequences. Their lengths(i.e. the number of repetitions)vary among individuals.

Proteomic studies at the GAC

The GAC provides the facilitiesrequired for the analysis ofcomplete proteomes, complex


Up to twelvesamples can bepipetted manu-ally at the same

time using amulti-channel

pipettor.Foto: B. Müller

protein mixtures or sub-proteo-mes from organelles. Instru-mentations for protein separa-tion processes are as well main-tained. Biomarker profiling isperformed with SELDI-MS (sur-face enhanced laser desorptionionisation mass spectrometry).

Protein identities are verified byvarious mass-spectrometrictechniques (such as MALDI-TOF). Protein interactions canbe assessed qualitatively aswell as quantitatively (e. g. withsurface plasmon resonance –SPR).

After separatingproteins by char-ge and molecularmass in 2D-PAGE,the molecules aremade visible bystaining.Foto: B. Müller


3. Major Scientific Interests ofGroups working at the GAC

Research Unit „Epidemiology –

Biological Samples – Genomics“

Head: Dr. Thomas Illig from theInstitute of Epidemiology (Head:Prof. Dr. Dr. H.-Erich Wichmann)

The research unit is integratedinto the Genome Analysis Centerof the GSF. The objective of thegroup is the genetic analysis ofcomplex diseases like type 2 dia-betes, cardiovascular diseases,atopic eczema, lung cancer orneurological disorders.

Expertise

The unit has great experienceconcerning high throughput ge-notyping projects and has publis-hed several manuscripts in thisfield. Several genetic associationstudies for different complex di-seases and intermediate quantita-tive phenotypes in large Caucasi-an case-control and family stu-dies have been performed. Thestatistical analysis of the results isdone in close cooperation withthe research unit 'Genetic Epide-miology' of the institute. Thegroup is responsible for the biolo-gical materials of the institute.

Infrastructure

A biological specimen repositorythat includes DNA, serum, plas-

ma, urine and immortalized celllines from large population ba-sed cohorts including the fa-mous KORA project has beenestablished. KORA is a popula-tion based, representative, Ger-man study including 18.000adults, from which biologic ma-terial is available. KORA hasbeen used as genetic control po-pulation for more than 70 studiesmostly from Germany in the lastfew years. Additionally biologi-cal materials from disease focu-sed studies like myocardial in-farction, type 2 diabetes or lungcancer are also available. Thesebiological materials are subjec-ted to molecular high through-put analyses in the GAC of theGSF. A main working field in thiscontext is the use of the highthroughput genotyping and se-quencing facilities, offering seve-ral different genotyping systems(e.g. MALDI-TOF MS, Affymetrix)for different kind of projects.

SNP Genotyping Platform

Responsible: Dr. Peter Lichtnerfrom the Institute of Human Genetics (Head: Prof. Dr. Thomas Meitinger)

The search for disease suscepti-bility genes through linkage andassociation studies constitutes acrucial component of most clini-


cal projects. A major focus is theidentification of genes related towidespread diseases such as di-abetes, asthma, Parkinson disea-se, or myocardial infarction. Thisrequires a facility specialised inhigh-throughput SNP genoty-ping both on the side of techno-logy and on the side of well trai-ned personnel. To promote thisgoal the GSF has built the infra-structure in the form of a genoty-ping core facility that is part of

the Genome Analysis Center.Progress in the technologicalfield together with the knowled-ge of linkage disequilibrium (LD)patterns in the human genomehas made genome-wide associa-tion studies a reality. The Affy-metrix 100K and 500K chips ena-ble genotyping of more than100,000 or 500,000 SNPs, respec-tively, in one experiment. Thiswill undoubtedly help identifyingmany new susceptibility genes

The activity ofalmost all genesof a tissue at acertain time point can beexamined byDNA chips.Known DNAportions areapplied to thechips, whichbind to comple-mentary, markedfragments in thesamples. Afterthat, fluorescen-ce shows whichgenes are activein the samples.Foto: B. Müller


responsible for common humandiseases. However, a genome-wide association scan is only afirst step in our search for disea-se genes. All results from thoseanalyses have to be replicated inindependent patient cohorts. Inthe end a fine mapping approachwill lead to the disease gene oreven to the causative variant inthis gene. This requires genoty-ping technologies that are bothflexible in SNP selection andcost-effective.

Infrastructure

The genotyping platform offers arange of complementary genoty-ping methods and possesses in-strumentation for SNP analysesincluding two mass spectrome-ters (Sequenom), a GeneChip ar-ray station (Affymetrix 10K,100K, and 500K arrays), and anABI7900 HT Taqman (AppliedBiosystems). The Affymetrix in-strumentation with six fluidicsstations for washing and stai-ning and two scanners with autoloaders has a processing capaci-ty of 300 GeneChip arrays (10K,100K, and 500K) per week. It isthe backbone for genome-wideassociation studies. Replicationstudies or saturation experi-ments of particular genomic re-gions are performed on a Seque-nom MassArray system. Withthe new iPLEX assay we can pro-

duce up to 500,000 genotypes ina week. Projects with small num-bers of SNPs but very large num-bers of samples can ideally beprocessed on an ABI7900HT Taq-man machine that has a capacityof 10,000 genotypes per week.

Mouse SNP Genotyping

Research Unit

Responsible: Matthias Klaften from the Institute of Experimen-tal Genetics (Head Prof. Dr.Martin Hrabé de Angelis).

Due to the similarity in genomes,developmental, biochemical andphysiological pathways, themouse has become the model ofchoice for the study of inheriteddiseases in man. To identify no-vel mutations correlating to thesegenetic defects, our institute hasestablished a research centre thatcarries out a large-scale ENU-mouse mutagenesis screen. Anumber of participating researchgroups screens the mice for spe-cific abnormalities like congenitalmalformations, clinical-biochemi-cal alterations, immunologicaldefects and complex traits. Themutant lines are analysed by dif-ferent mapping strategies andgenome wide high-throughputSNP genotyping to identify thechromosomal locus of the muta-tion. This data provides the star-


ting point for researchers to iden-tify and characterise the underly-ing gene defect or allelic variantcausing a specific trait.

Expertise

We have established a pipelinestarting from the selection of ap-propriate mouse strains andbreeding strategies, over the se-lection and validation of SNPmarkers, to the preparation, ge-neration and interpretation ofthe genotyping results. Over 100mouse lines have been mappedfrom various projects until theend of 2005.The mouse SNP genotyping unithas in depth knowledge of auto-

mated DNA extraction frommouse tissue and SNP genoty-ping using large sets of markersand samples. We are also focus-sing on the development of bio-informatic tools that allow rese-archers to generate genotypingassays and to administrate andinterpret the data obtained fromthe genotyping experiments.

Infrastructure

DNA is extracted from mouse tailsamples on a Tecan FreedomEvo 150 robotic workstation withan average throughput of 500samples per week. Genotypingof 368 DNA preparations (repre-senting up to eight different

DNA moleculesstained with ethi-dium bromideglow under UVlight, and bandsof different-sizeDNA fragmentsbecome visible.Foto: B. Müller


mouse lines) with 136 SNP mar-kers is performed on the Seque-nom MALDI-TOF MS genotypingsystem consisting of several robotic workstations and MJ Research Tetrad Thermocyclers.

Gene Regulation and Expression

Profiling Group

Head: Dr. Johannes Beckers from the Institute of Experimen-tal Genetics (Head: Prof. Dr.Martin Hrabé de Angelis)

The understanding of the func-tional regulation between trans-criptome and proteome is cur-rently limited to distinct signal-ling or metabolic pathways. Inthe Human Brain Proteome Pro-ject 2 (HBPP2 is part of NGFN2)we analyse these mutual regula-tory interactions in the context ofhuman neurodegenerative disea-ses. To this end, we focus on theprogressive changes at the RNAand protein levels in mouse mo-dels for Alzheimer’s disease andParkinson. The transcriptomeanalysis is done by using a stateof the art Affymetrix work stationin combination with our in house20k cDNA microarray.The German Mouse Clinic at theGSF (www.mouseclinic.de) offersthe examination of mouse mu-tants using a broad standardisedphenotypic check-up of more


The SNP geno-typing is perfor-med on seque-

nom MALDI-TOFmass spectro-

meter. The approach is

automated andthe operator has

full control onthe process or

quality of data.Foto: J. Adamski

than 250 parameters. As part ofthis primary screen a molecularphenotyping is carried out usingour in house 20k cDNA microar-ray. This close to genome-widetranscriptome analysis providesinformation about genes, whichare differentially expressed bet-ween mutant and wildtype micein selected organs and thus provi-des the molecular basis for theobserved phenotypes.The evolutionary conserved Del-ta/Notch signalling pathway re-gulates the determination of va-rious cell fates and differentia-tion processes. To study the im-pact of this pathway on somit-ogenesis, we generated a panelof mutant mouse lines by trans-gene or knock-out technologies.

ExpertiseWe have in depth knowledge inthe production of genome-widecDNA microarrays employing ro-botic systems as well as the useof these arrays for transcriptomeanalysis. We also use the Affy-metrix GeneChip system and ar-ray results are validated by RealTime PCR, in situ stainings, or bythe generation of mutant mouselines. In addition, comparativeapproaches for the combinedanalysis of transcriptome andproteome are performed.

Infrastructure

cDNA microarrays are producedon a Microgrid Tas II (Biorobo-tics, 90 slides/48 h) from theLion ArrayTag library, which is


The processingof microarraysrequests stan-darized hybridi-zation and was-hing steps. The-se are perfor-med in parallelto improvethroughput.Foto: J. Beckers

amplified on a Tecan robotic system (Genesis Pipet Robot,MG Research Tetrad PCR cycler;capacity: 1000 PCR in 24 h). Ar-rays are hybridized on a TecanHybstation HS4000 (24 arrays/day) and analysed on an Axon4000A or a Tecan LS400 scanner(both 96 arrays/day). The Affy-metrix GeneChip Workstation(Fluidics station 450, Scanner3000; 200 arrays/day) is suitablefor all available GeneChip ar-rays, including the latest SNPand tiling arrays.

Plant Research Unit

Responsible: PD Dr. AntonSchäffner from the Institute ofBiochemical Plant PathologyHead: PD Dr. Jörg Durner (provisional)

Environmental cues are percei-ved and processed by plantsthrough complex mechanisms.An important aspect in elucida-ting these mechanisms is theidentification of genes involvedin defense and signal transduc-tion after imposing an externalstress. Thus, we could identifygenes involved in pathogen de-fence, and in response to saltstress and UV irradiation. In a si-milar manner, alterations of geneexpression profiles are used toinvestigate the impact of indivi-

After hybridiza-tion microarrays

can provide in-formation on

gene expressionlevels which are

read out by fluorescence

signals.Foto: GAC


dual genes after their mutagene-sis or transgenic expression. Thediagnostic tools to answer thesequestions are DNA arrays whichare primarily custom-designedand produced. The most impor-tant model organism is Arabi-dopsis thaliana, however thereare also projects using beechtrees, the metal hyperaccumula-ting Thlaspi and the marine algaLaminaria. The crop plants barleyand maize are also used for ex-pression analyses.For smaller groups of genes orto verify array analyses, the in-frastructure for quantitative RT-

PCR is used at the GAC. Finally,the GAC sequencing facilities as-sist the controling of DNA frag-ments in cloning experimentsand in the production of DNA arrays.

Expertise

Design, production, and analysisof DNA arrays for expressionprofiles of plants using radioac-tive and fluorescence-based de-tection; supervision of the Micro-Grid II roboter; quantitative RT-PCR; immunological quantitationof proteins; analyses of plantmetabolites.

Mouse-ear cress(Arabidopsisthaliana) is amember of the mustard family(Brassicaceae).It is often usedas a model orga-nism in geneticsand molecularbiology.Foto: BIOP


InfrastructureBioRobotics Spotter MicroGridII for production of DNA arrayson glass slides and nylon mem-branes; ABI 3100 Sequencer(approximately 1000-1500 runsper year), Applied Biosystemsquantitative RT PCR (approx. 2runs per months), Fuji Fluoroi-mager FLA 8000 (in building.22/032), Fuji Fluoroimager FLA3000.

Molecular Endocrinology and

Proteomics Group

Head: Prof. Dr. Jerzy Adamski from the Institute of Experimen-tal Genetics (Head: Prof. Dr. Martin Hrabé de Angelis)

Several human multifactorialdiseases such as breast or endo-metrium cancer, endometriosis,osteoporosis, CHILD syndrome,cardiovascular diseases andfurther severe disorders of neu-ronal and renal developmentsuch as Zellweger syndrome,adrenoleukodystrophy orSmith-Lemli-Opitz syndromeare associated with abnormalmetabolism of sterols, steroidsand fatty acids. Our interest isto identify the factors, both atthe genomic and proteomic le-vel, responsible for the abovepathological processes, to esta-blish novel diagnostic tools and

develop targeted new and safemedicines. We analyse structu-re-function relationships of pro-tein families involved in the ae-tiology of steroid-related hu-man diseases. We significantlycontributed to the understan-ding of molecular basis of D-specific bifunctional protein de-ficiency by identification andcharacterization of 17beta-hydroxysteroid dehydrogenase4. Our group identified the lastunknown human enzyme ofpostsqualene cholesterol bio-synthesis, a novel 3-ketosteroidreductase. We have at presentthree patents for enzyme-speci-fic inhibitors designed for thetreatment of prostate cancer orendometriosis. We have usedmouse mutants to study me-chanisms of vitamin D actionand sterol metabolism.

Expertise

We routinely perform gene ex-pression analyses like: in silicoNorthern, in situ hybridisation,phylogenetic assays, DNA-chipand protein macroarray techno-logies. The functionality of ge-nes is facilitated by analyses ofpromoter function by reportergenes like luciferase in cell cul-ture and subcellular localizationstudies of transiently transfec-ted cells. For the proteomicaland metabolomical studies we


undertake recombinant proteinexpression and purification andprotein-protein interaction as-says like yeast two hybrid as-say, surface plasmon resonance(SPR from Biacore). We are lea-ding group in enzymatic assaysfor kinetical characteristics andinhibitory capabilities with TLCand HPLC with UV and radioac-tive detection. We apply massspectrometry for the identifica-tion of small molecules (GC-MS) and peptides (MALDI-TOF,SELDI) separated previously by

2D-gel electrophoresis or chro-matographic procedures. Ourmain expertise lies in the com-parative genomics and proteinchemistry of enzymes of sterol,steroid and fatty acid metabo-lism in human, mouse and zebrafish.

Infrastructure

Protein interaction partners canbe further characterised by sur-face plasmon resonance (Biaco-re) to envision the kinetics andaffinities of processes. Our

Structure-func-tion analyses fa-cilitate develop-ment of specificand safe medici-nes. Picture de-monstrates the3D-structure ofHSD17B4 enzy-me with cofactor(green-blue) andsubstrate (yel-low).Graphics:J. Adamski


metabolomical approaches inmetabolism of sterol, steroidand small lipophilic moleculesare facilitated by TLC and HPLCwith UV and radioactive detec-tion involving state-of-the-artrobotics for handling of 96-wellplates (Tecan) followed by massspectrometry for the identifica-tion of small molecules (GC-MS) and peptides (SELDI).

Research Unit Genetics & Mole-

cular Mechanisms of Disease:

Functional Proteomics

Head: Dr. Marius Ueffingfrom the Institute of Human Genetics (Head: Prof. Dr. ThomasMeitinger)

Expertise

Interactions between genetic andenvironmental factors determinedynamics of normal cell functionas well as the risk, penetrance,

onset and progression of disea-ses. Complementing the verysuccessful classical gene disco-very strategies that aim at eluci-dating the genetic contributionto disease, proteomic analysiscan assist in understanding disease mechanisms as proteinexpression and -function integra-tes genetic and environmentalcontributions to disease.The scientific focus of the groupwithin the Institute of HumanGenetics lies on molecular me-chanisms of neurodegenera-tion. Methodologically, thegroup covers in depth expertiseon protein identification as wellas on the analysis of functionalprotein-protein interactions,especially interactions involvedin signalling, protein proces-sing, – modification and – turn-over. Biochemical and proteo-me analysis are combined withfunctional tests in living cells or

Subcellular loca-lization of a pro-tein is importantfor its functiona-

lity. Wild typeHSD17B4 is

peroxisomal (leftpanel) whereastruncated pro-

tein is cytosolic(right panel) and

undergoes fastproteolysis. Bar

10 μm.Foto: J. Adamski


animals. Based on funding fromBMBF (NGFN2) and EU (inclu-ding INTERACTION PROTEO-ME, the EU’s largest proteomicsproject), we have focussed onthe development and applica-tion of methods for functionalproteome analysis. Our approaches are largely ba-sed on gel-free separation of topologically organised cellularsub-proteomes, including nati-ve multiprotein complexes, bynative separation methods andon the digestion of cell lysatesand complex peptide mixturesrather than on conventional gel-based protein separation sys-tems. For the analysis of sub-cellular entities and proteincomplexes we preserve nativeconditions employing native se-paration protocols, or work withaffinity tags that were recentlydeveloped in the group.

InfrastructureWe use gel-based as well as gelfree separation techniques to se-parate large proteomes or enrichspecific sub-proteomes of inte-rest. Free Flow Electrophoresis(FFE) in combination with PAGE(1- and 2-DE) or liquid chromato-graphy is used to enrich and se-parate proteins prior to identifi-cation by mass spectrometry.FFE can be employed for sub-fractionation of whole organellesas well as for gel-free isoelectricfocusing of native protein com-plexes, for denaturing IEF-sepa-ration of single proteins and forsurface charge-dependent sepa-ration of cellular organelles. Incontrast to 2D-gel-based separa-tion, membrane proteins and ba-sic proteins are well represented.Mass spectrometry is performedby MALDI-TOF, LC-Q-TOF andLC-MALDI-TOF-TOF).



4. Who Can Use the GAC?

The GAC works as a platform ofexpertise and technology for allGSF institutes, provided theyhave a detailed project and theirown funds for consumables. Theactivities at the GAC are coordi-nated by a Steering Committee.The institute directors perfor-ming research at the GAC aremembers of this committee.The support is provided on acooperative basis, i.e. commonprojects. Only in a few areas likethe DNA-sequencing facility part

of the services is provided for acharge covering the runningcosts.

Further information:

www.gsf.de/ieg/services/gac

One tool of choi-ce for medium-throughput ge-notyping: The

MALDI-TOFmass spectro-

meter.Foto: Goddeng

Prof. Dr. Jerzy AdamskiTele: 089/3187-3155e-mail: [email protected]

GSF – National Research Centerfor Environment and HealthInstitute of Experimental Genetics

Dr. Thomas IlligTele: 089/3187-4249e-mail: [email protected]

GSF – National Research Centerfor Environment and HealthInstitute für Epidemiology

Contact

Head

Deputy


SNP Coordination

Proteomics Coordination

Dr. Peter LichtnerTele: 089/3187-3530e-mail: [email protected]

GSF – National Research Centerfor Environment and HealthInstitute of Human Genetics

Dr. Marius UeffingTele: 089/3187-3567e-mail: [email protected]

GSF – National Research Centerfor Environment and HealthInstitute of Human Genetics

GSF – National Research Center for Environment and HealthGenome Analysis Center

Ingolstädter Landstr. 1 • 85764 Neuherberg


Impressum

Publisher

GSF – National Research Centerfor Environment and HealthMember of the Helmholtz Association

Editors

Monika Gödde, Michael van denHeuvel, Heinz-Jörg Haury

Distribution

Brigitte Schmid

Editors address

GSF – National Research Centerfor Environment and HealthDept. of Public Relation,Ingolstädter Landstraße 1, 85764 NeuherbergTel.: 089/3187-2711, Fax: 089/3187-3324E-Mail: [email protected], Internet: www.gsf.de

Layout und graphic design

Der Buchmacher, Arthur Lenner,www.derbuchmacher.de

Printed by

Digital 2000 Medienzentrum

Pictures

Bernd Müller (www.buero31.de), Ingrid und Günter Goddeng,Ursula Baumgart, GSF-Archiv,Jerzy Adamski, Johannes Beckers.

Excerpts from this brochure maybe reproduced without furtherpermission, provided the GSF ismentioned in the publication. We ask for an author’s copy. All other rights are reserved.


Research for the Protection of Man and the Environment

The GSF – National Research Center for Environment andHealth – an institution of the Federal government and theState of Bavaria in the legal form of a GmbH – works outscientific foundations in order to sustainably protect humanhealth and the natural conditions for human life. GSF hasapprox. 1600 employees. The total budget is € 164 millionper year.

As a member of the Helmholtz Association, the largest pub-lic research organisation in Germany, the GSF contributesits work to the programmes of the research areas of „Earthand the Environment“ and „Health“.

The Genome Analysis Centre on the Neuherberg campus ofthe GSF – Research Center for Environment and Health

Foto: J. Adamski

GSF – National Research Centerfor Environment and Healthmember of the Helmholtz Association

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