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Page 1: The Genome: Key to Life - Norges forskningsråd · 2019. 3. 7. · In my FUGE – enhancing ... The Genome: Key to Life page ... material has been decoded, but we have not yet been
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opinion, this is extremelyproductive. Anotherimportant aspect that theGovernment wishes toemphasise is the excellentopportunity that FUGEprovides for stimulatinginternational research co-operation. Top researchersfrom abroad are recruitedto work in Norway, andNorwegian researchers areencouraged to carry out part of their research abroad.This will help to enhance our own expertise, while atthe same time promoting Norway as an attractivepartner on the international arena.

FUGE is a good example of how Norway can upgradethe quality of its research. The model has been appliedto other areas, and can thus already be said to haveachieved positive results. Now it is up to the authoritiesand research community to continue working togetherto further intensify these research efforts, so as toenable Norway – in a few years’ time – to assume aleading position in strategically important areas withinthe field of functional genomics.

Kristin Clemet

Minister of Education and Research

In an international perspective, biotechnology hasemerged as one of the top priority areas withinresearch. This field holds the key to new knowledgethat will increase global understanding of funda-mental biological processes and provide a basis forinnovation and industrial development. Norway, too,has recognised the vast potential of this field ofresearch, and has launched a national plan toenhance research in functional genomics (FUGE).

The FUGE research programme received an initialallocation of NOK 100 million over the 2002 nationalbudget. In 2003, funding was increased by an addi-tional NOK 50 million. A continuation of the allocationof NOK 150 million has been proposed in the budgetfor 2004. There are two primary objectives underlyingthe Government’s focus on the FUGE programme:Firstly, to raise the quality of Norwegian research inthis area to international standards, and secondly, topromote our national industrial development. At thesame time, the programme should facilitate the identifi-cation and utilisation of our national advantages, forinstance in the fields of marine research, environmentalprotection, agriculture and medicine.

In the Government’s view, one of the most importantelements of the programme is a national division ofresponsibilities within the context of a unified plan.FUGE is the first research programme in Norway toincorporate clearly defined national as well as regionalmodes of interaction and distribution of tasks. This hasled to new lines of thinking and cooperation across theboundaries of disciplines and institutions. In my

FUGE – enhancing national research in functional genomics

The Genome: Key to Life page

Excellent Returns from Functional Genomics

A National Plan Objectives Restructuring of the Norwegian Research Establishment

FUGE – More than Basic Research

The FUGE Tool Box

The Technology Platforms page –

Biobanks for Health

Bioinformatics

Integrative Genetics and SNP Analysis

Microarray Technology

Proteomics

Structural Biology

Molecular Imaging

Transgenic Mice

Microbial Science

Functional Plant Genomics

FUGE’s Administration (contacts)

Contents

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Biological processes are at the core of much of humanactivity, from fulfilling the fundamental needs of thebody, through commercial activities such as fisheries,aquaculture and agriculture, to environmental protec-tion and methods for dealing with medical problems. Ineach of these areas, functinal genomics is expected togenerate new insights and a variety of pioneeringproducts and methods. These will include new pharma-ceutical products and medical treatments, new methodsto increase the food production output of aquacultureand agriculture, methods to enhance the quality, e.g.nutritional status, of food products, and methods toremove or neutralise hazardous substances.The new knowledge and technological possibilitiesbrought about by research in functional genomics willalso raise new questions relating to the legal, ethicaland social aspects of these activities. It is thereforeimperative that research be conducted on these aspectsof functional genomics as well. The opportunitiesinherent in functional genomics research must beconveyed to the community at large as a basis forpublic debate.

The genome comprises the complete genetic material, orthe DNA, of each living organism. The genome containsall the information that is needed for an organism toexist, as well as the codes that give each species and eachindividual its own unique make-up. It consists of about, genes, each of which contains the code for otherproducts in the form of proteins that have variousfeatures and functions within the organism. In the pastdecade, the human genome and the genomes for anumber of other species have been mapped. The geneticmaterial has been decoded, but we have not yet beenable to completely decipher its message.

Functional genomics encompasses research to interpretthe code and understand the intricate processes bywhich the genes and proteins in an organism function,alone and in interaction with one another. New techno-logies in this sphere are emerging at a phenomenalpace. Functional genomics is a wide-ranging and com-plex research field, and is thus by nature an interdisci-plinary undertaking. It integrates not only biology andbiomedicine, but also chemistry, physics, mathematics,informatics, statistics and more.

The Genome: Key to Life

The mapping of the genetic material(genome) of humans and many otherorganisms represents a new era in science,and paves the way for a completely newunderstanding of the processes takingplace in living organisms. This is the basisfor the research programme in FUnctionalGEnomics (abbreviated FUGE ), whichopens the door for a host of new prospectsand challenges. Research activities must be organised in a

different fashion if we are to succeed in taking fulladvantage of these new opportunities. The need foradvanced, high-cost technology and broadly differen-tiated know-how requires cooperation between manydifferent research environments. FUGE represents aninitiative in which the academic institutions within theuniversity regions have agreed to allocate tasks andutilise shared resources and know-how. At the root ofthese efforts lie the national technology platformsthat have been launched to serve as competence centresresponsible for developing their specific technologies inNorway. In addition to providing services and assistanceto the research community at large, each centre will offertraining for researchers and technicians as well asconduct its own research activities.Norwegian society will benefit in great measure fromincreased research in functional genomics. This sphere ofresearch is based on biotechnology that will form thebasis for much of the industry of the future. The primaryobjective of the FUGE programme is to enhance the

quality of basic biological, medical and marine research,and to help to ensure that this research is in turn imple-mented to generate innovation and strengthen industrialdevelopment.Top-quality national research is also an important door-opener to participation in developments taking place inother countries, and will bolster Norway’s ability to takepart in the international arena. FUGE will provideNorway with the academic authority and cohesive voiceneeded to form alliances and establish cooperation withsimilar research programmes abroad. National researchprogrammes are expected to play a central role in thedevelopment of the EU’s Sixth Framework Programme aswell as the European Research Area. FUGE will alsogenerate benefits in terms of improved recruitment andeducation of researchers within priority research areas. The challenges facing us are many. FUGE’s nationaltechnology platforms need to be distilled into a dynamicresource. FUGE will also establish the expertise needed toelucidate and clarify the ethical, social and environ-mental consequences of research in functional genomics.Nonetheless, the most important factor for success will befound in our ability and willingness to cooperate –internally within our research community as well asexternally, vis-à-vis industry, investors and the govern-ment authorities.

Ole Petter OttersenFUGE Board Chair

Excellent returns from functional genomics!

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strategic importance or in which it has special nationaladvantages. Medical research: FUGE will make it possible forNorwegian health care services to utilise the newknowledge and products that result from functionalgenomics, thus ensuring that Norwegian health careremains among the best in the world. Marine research: FUGE will play a role in establish-ing the knowledge base needed to promote furtherdevelopment of the aquaculture industry and optimalutilisation of Norway’s marine resources. It is alsoimportant to facilitate the establishment of a biomarineindustrial cluster in Norway.Ethical, environmental and social issues:FUGE will enable Norway to acquire knowledge aboutthe consequences and dilemmas inherent in functionalgenomics research in order to supplement the publicdebate and help to maximise the potential positiveimpact of such research on society, the environmentand the individual.

Restructuring the Norwegian ResearchEstablishmentNational and regional allocation of responsibilityFUGE establishes a baseline technological capacity infunctional genomics in each of the four universityregions. Each region has been allocated responsibilityto build up know-how and services in certain fields,and together they can supply the national researchcommunity with the services it needs. The regions areresponsible for cooperating among themselves, as wellas for maintaining contacts with the internationalresearch community. Industrial developmentFUGE is part of a long-termnational effort to generateresearch-based industrialdevelopment. FUGEcooperates with commerciali-sation entities in each of theregions to strengthen theinteraction betweenuniversities, universitycolleges, other research institutions and the industrialsector. InternationalisationIt is an expressly stated objective that Norwegianfunctional genomics research is to be of top scientificquality. To achieve this, it will be necessary to recruitoutstanding international researchers with broad-basedinternational networks to come and work in nationallaboratories. At the same time, researchers in Norwaymust be encouraged to seek entry into eminent researchinstitutions and communities abroad. FUGE providessupport for both of these measures.

At the sametime, FUGEcomprises a planfor restructuringand increasingthe efficiency ofthe researchestablishment. Itis vital thatNorway’s overallresearchresources andexpertise beutilised aseffectively aspossible. Underthe FUGEprogramme,responsibilities

and tasks are delegated to the four university regions,and new models for cooperation between universities,research institutions and the industrial sector will bedevised. This will help to make Norwegian researchinstitutions attractive abroad, and ensure that Norway isconsidered an interesting candidate for equal partner-ship in international collaborative projects.

At the Nordic level, FUGE is in contact with similarinitiatives (such as SWEGENE), and is establishing aframework for cooperation and shared utilisation ofresources. FUGE’s action plan integrates many featuresof the EU’s Sixth Framework Programme, and providesassociated researchers with an excellent basis forparticipation in EU projects.

FUGE encompasses three priority areas: Basic biologi-cal research (including bioinformatics), marineresearch and medical research. Within each of theseareas, industrial development is a topic of mainconcern. In addition, funding is provided for researchon ethical, environmental and social issues that need tobe brought to light and clarified in relation to func-tional genomics.

Objectives

FUGE is designed to enhance Norwegian research infunctional genomics in the following areas:Basic biological research: FUGE will strengthen basicbiological research and will help to ensure that Norwayemerges as a prominent player in areas of particularly

A National Plan

FUGE comprises a national plan for research in func-tional genomics in Norway. The plan is designed tostrengthen research in this field to bring Norway up totop international standards.

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Ethics, society and the environmentThe application of biotechnological methods to areasinvolving health, food and the environment is a topic ofheated public debate. It is critical that all scientific andtechnological development takes place in keeping withthe values and norms on which society is based.However, at times along the way, the reigning attitudesand norms may be challenged. FUGE has set aside a maximum of five per cent of itsbudget for research projects on the ethical, social andenvironmental aspects of functional genomics.Activities include legal projects on patent legislation,regulation of access to genetic information, and thegeneral public’s need for and right to information.FUGE also funds social science projects on healthpolicy, equitable distribution and on the attitudes andknowledge of the population. In addition, funding hasbeen provided for environmental projects in connectionwith aquaculture.

Industrial developmentFUGE is designed to help identify ideas that havecommercial potential, and will thus enable functionalgenomics research in Norway to lead to the develop-ment of new products. FUGE will stimulate industrialdevelopment and job creation through activities such aspromoting the entrepreneurial awareness of researchers,enhancing cooperation with commercialisation entitiesin the university sector, and supporting emerging andestablished biotechnology industries. A maximum often per cent of the FUGE budget has been set aside forthese measures, primarily with an eye to supportingactivities that can be built up in Norway but that will atthe same time be of value in the international arena.Opportunities worthy of further development havealready been identified in the medical and analyticalspheres, and great importance is attached to thetremendous potential of the marine sector, whereFUGE will also work to promote innovation.

Eleven National Technology PlatformsFunctional genomics requires advanced technology andhighly-educated personnel. In light of this, nationaltechnology platforms have been established as the pillars ofthe FUGE programme. These platforms have been delegated national responsibilityfor developing their capacities and will become technicalservice centres providing special expertise and know-howwithin the applicable technologies. These platforms provideseminars and meetings for users throughout Norway. Inaddition, they conduct international research activities toenhance the development and utilisation of the platformtechnology.

The FUGE Tool Box…

High returns on research!Functional genomics offers many benefits. For example, research in this spherecould make it possible to reduce the pigment costs for farm-raised salmon by per cent, and still obtain the appropriate flesh colour.The savings are enormous:

Current salmon production: ,, kg per year Pigment costs: NOK ./kg % cost reduction in pigment costs due to research and improved understandingof biological processes:,, kg x NOK . x % x years = NOK , billion saved

The precautionary principleIn Norway, it is established practice to view gene technology re-search as subject to the precautionary principle. Thus, the conse-quences of utilising the know-how derived from such research mustbe carefully weighed, and the use of this know-how will not beapproved if an unacceptable measure of risk is found to exist.The precautionary principle and risk assessments are applied in situ-ations such as those involving the dispersal of modified organismsinto the natural environment, or the introduction of new treatmentmethods and technologies that cause permanent or temporarymodification of an organism’s genetic material.

FUGE – More than Basic Research...Part of the allocations to FUGE are earmarked for industry-oriented research andresearch relating to ethical, social and environmental aspects of functional genomics.

Photo: P. E. Lillholm, PROBE

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Core tasksTo develop a genealogy databank, i.e. a database thatcompiles genealogical data. This is necessary in orderto conduct studies on genetically inherited factors. Thisdatabank is being developed in cooperation withStatistics Norway (the Norwegian central bureau ofstatistics). To increase Norwegian expertise in genetic epide-miology and biostatistics by means of recruitment andcooperation with international research centres.To conduct DNA extraction to isolate DNA fromblood samples for genetic analysis. This is a demandingand costly task. Biobanks for Health utilises a DNAextraction robot to facilitate the extraction process forblood samples. To create an IT system that makes it possible to linkinformation on biological material from individualstogether with health and genealogical data.To establish common ethical guidelines as a basis forethically responsible management of the material.These guidelines will apply to the access of researchersto data and biological material. All data collectionactivities have been approved by the Norwegian DataInspectorate and the National Committees for ResearchEthics in Norway.To conduct research through participation in scientificprojects in cooperation with Norwegian and foreignresearch groups on scientific projects that incorporatethe technology platform.

OrganisationThe Norwegian Institute of Public Health is the hostand coordinating institution for the Biobanks forHealth. The Faculties of Medicine at the fourNorwegian universities are all cooperating on thisplatform. The Regional Research Biobank for CentralNorway is located at the Norwegian University ofScience and Technology and collaborates closely withthe Central Norway Regional Health Authority andother biobanks, including Biobanks for Health.

ContactPlatform Coordinator, Biobanks for Health: DivisionDirector Camilla Stoltenberg, Division for Epidemiology,Norwegian Institute of Public Health, OsloPlatform Coordinator, Regional Research Biobank forCentral Norway: Senior Lecturer Jostein Halgunset,University of Science and Technology, Trondheim

E-mail: [email protected],[email protected]: www.fhi.no/tema/biobank

A genetic reference guide...The causes of human disease are both genetic andenvironmental. In order to provide a better under-standing of disease patterns among the population,health information is compiled in databanks known asbiobanks. These contain biological samples as well asinformation about peoples’ health, illnesses, environ-ments and life histories. By linking this informationtogether, it is possible to learn more about the separateand combined effects of genetic factors and environ-mental influences on health. Knowledge about genetictraits can help to improve preventive health care effortsas well as the treatment of disease. Data is being addedto the biobanks on an ongoing basis, and thus theyrepresent an important resource for the future as well asfor the present.

Main responsibilities and activitiesTwo technology platforms have been established in thissphere of research: the Norwegian Network of HumanResearch Biobanks and Health Studies (Biobanks forHealth) and the Regional Research Biobank for CentralNorway. These platforms are responsible for establish-ing an operational network between Norwegian healthstudies and human research biobanks. The Biobanks forHealth platform builds on the regional health studiesthat are cooperating on the Cohort of Norway(CONOR) and the Norwegian mother and child(MoBa) studies. These studies compile health informa-tion, clinical measurements and blood samples fromthe Norwegian population, and currently encompassdata from roughly 230,000 individuals. When com-pleted, the network will comprise biological samplesand standardised health and exposure data from 450,000Norwegian individuals of all ages, corresponding toapproximately 1/10 of the Norwegian population. Thisdata will provide a unique basis for medical research,especially research to study the interaction betweengenetic and environmental causes of disease.The Regional Research Biobank for Central Norway is

a national pilot project launched to assessvarious issues, such as the organisational andlegal implications of human researchbiobanks.

The platforms are responsible for stimulatingresearch projects and facilitating the optimalutilisation of data and biological material. Themost important task in coming years will be tosupply new knowledge that can lead to en-hanced prevention and treatment of disease.Such knowledge will encompass discoveriesof new genes associated with complexdiseases and new information regarding thesignificance of environmental factors.

Biobanks for Health

The Technology Platforms

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OrganisationThe platform is a joint project hosted by the Universityof Bergen, the University of Oslo and the NorwegianUniversity of Science and Technology in Trondheim.The University of Bergen is the coordinating partner,and has the overall responsibility for platform activi-ties. The platform also incorporates activities from anumber of other research and educational institutions inthe Oslo area, including the Norwegian RadiumHospital and the Norwegian Computing Centre. Inaddition, several commercial enterprises are involved,including Sencel AS, PubGene AS and MolMine AS.

ContactPlatform Coordinator: Professor Inge Jonassen,Department of Informatics, University of Bergen

E-mail: [email protected]: www.bioinfo.no

Interpretation and translation… The “language” of the genes is difficult to understand,but with the help of computer technology, the codes canbe cracked and the book of life can be read.Bioinformatics is an interdisciplinary science thatanalyses biological data using methods from informatics,statistics and mathematics, among others. In cooperationwith its users, the platform for bioinformatics will workto develop methods and models that can provideNorwegian functional genomics researchers with thetools that they need.

Main responsibilities and activitiesThe platform for bioinformatics is responsible forproviding research-based services and training inbioinformatics, and for creating a technologicalfoundation that may be utilised by other FUGEplatforms as well as other researchers. The platformconducts research in theoretical bioinformatics(development of models and methods) and appliedbioinformatics in biological or biomedical researchprojects. The platform supplies services such as data-bases and analysis software both nationally and abroad. The platform will take active part in Norwegianfunctional genomics and biomedical research, and willbe a hub for a substantial network of internationalcontacts. To achieve this, it is necessary to encouragecloser cooperation between the research communityand the industrial sector.

Core tasksTo provide services such as web-based databases andtools, advisory services and programming assistance.To arrange courses and training programmes oncentral bioinformatics topics as well as a visitor’sprogramme in which researchers can work directly withplatform personnel for shorter or longer periods oftime. To conduct research in areas such as methods foranalysis of gene expression data, evolutionary studies,clinically-oriented bioinformatics, structural biologyand biological databases.

Bioinformatics

The Technology Platforms

Biobanks for healthColumbia University researchers, in collaboration with researchers at the NorwegianInstitute of Public Health, have received a five-year, USD million grant from the USNational Institutes of Health to fund one of the world’s largest studies of neuro-developmental disorders. The study (nicknamed the "baby Framingham" project) willtrack babies before they are born. Initially focused on autism, the study will follow upto , pregnancies from the first trimester through childhood – and possiblyadulthood – via access to a birth registry in Norway and the “Mother and child”biobank. This interdisciplinary study provides a unique opportunity for Columbia andthe Norwegian Institute of Public Health to conduct rigorous examination of theroots of autism and other neurodevelopmental disorders. Findings will be crucial inthe context of improving global health.More information: http://www.fhi.no/publ/nyheter/---autisme.html

Ill.: V. Eijsink, NLH

Ill.: Moe and Klungland, Rikshospitalet University Hospital Oslo

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Core tasksTo provide a national service centre for the analysisand typing of point mutations (SNPs) on a large scalein biological material from humans, micro-organisms,plants, animals and fish.To provide a national competence centre for theidentification and methodological integration ofexperimental and theoretical methods to build bridgesbetween genome information and phenotype character-istics in general.To serve as a core partner in salmon and bovinegenomics.To organise courses and seminars, host national andinternational meetings and conferences, and provideadvisory services to researchers.To conduct research by participating in scientificprojects in cooperation with Norwegian and foreignresearch groups.

OrganisationCIGENE is a cooperative effort between theAgricultural University of Norway, the NorwegianSchool of Veterinary Science, Akvaforsk ResearchInstitute, the Norwegian Radium Hospital, theUniversity of Oslo, the Norwegian University ofScience and Technology and the Norwegian ComputingCentre. Each of the university regions is represented onCIGENE’s board, which also includes representativesfrom Norwegian biotech industry.

ContactPlatform Coordinator: Professor Stig W. Omholt,Department of Animal Science, Agricultural Universityof Norway, Ås

E-mail: [email protected]: www.cigene.no

From genome to function…Why do we look and function the way we do? How canwe be so different and yet so alike? The appearance andcharacteristics of an organism comprise its phenotype,and are a product of both genetic and environmentalfactors. Tiny differences in the genetic make-up can leadto great differences in phenotype.A gene is “coded” around four different nucleotides.Sometimes, one of these nucleotides is replaced byanother, causing a point mutation known as a SingleNucleotide Polymorphism (SNP). SNPs may be used tofind genes that influence disease in both humans andanimals, as well as genes that are significant for com-mercially important traits in plants, fish and mammals.

Main responsibilities and activitiesThe platform for integrative genetics focuses on thedetection, typing and interpretation of variationsbrought about by point mutations. This platform ishosted by the Centre for Integrative Genetics (CIGENE).

CIGENE is intended to be a highly visible player in thefield of integrative genetics. The platform is respon-sible for facilitating a deep causal understanding ofcomplex genetic characters in fish, plants and animalsfor scientific as well as commercial exploitation.

Integrative Genetics and SNP Analysis

Integrative geneticsBoth organisationally and scientifically, CIGENE is participating in thechanges taking place in genetics research:• Experimental and theoretical approaches are being integrated in

concrete interdisciplinary research programmes.• The processes and mechanisms which in the broadest sense link

genotype data to phenotype data are being integrated by means of mathematical, statistical and computational tools.

• - In functional genomics, traditional scientific barriers between biomedical research, evolutionary biology and production biology cease to exist.

The Technology Platforms

Photo: T. Becker, Sars Centre, Univ. of Bergen

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OrganisationThe NMC is a collaborative effort between theUniversity of Oslo, the Norwegian Radium Hospital,the Norwegian University of Science and Technologyand the University of Bergen. There are operative plat-form centres at each of these sites. Cooperation alsoincludes the development of methodology as well asresearch and education within the field of microarraytechniques.

ContactPlatform Coordinators (rotating)Professor Vidar M. Steen, Centre for Medical Genetics and Molecular Medicine,University of Bergen (Platform Coordinator, )Professor Ola Myklebost, Institute for Cancer Research, the Norwegian RadiumHospital, Oslo (Platform Coordinator, )Professor Astrid Lægreid, Institute for Cancer Research and Molecular Medicine,Norwegian University of Science and Technology,Trondheim (Platform Coordinator, , )

E-mail:[email protected]/[email protected]: www.mikromatrise.no

When thousands of genes need to be compared…Living cells contain approximately , genes thatwork together and influence one another. To enablescientists to understand how this takes place, a specialtechnology for studying all of the genes at the same timehas been developed. This method is called DNA micro-array technology, and it is utilised to monitor variationsin gene activity under different conditions. Microarraytechnology makes it possible to obtain better diagnosesand a better understanding of disease, as well as todevelop pharmaceutical products that are specificallydesigned to provide the most effective treatment of theindividual patient.

Main responsibilities and activitiesThe microarray technology platform is responsible forsupplying researchers with access to high-quality DNAmicroarray technology. The platform follows inter-national developments in this technology sphereclosely, and plays an active role in defining the re-search tasks in which to apply microarray technology.This ensures that the platform will be able to providethe research community with the best possible supportwith regard to array-based laboratory techniques. Theplatform for microarray technology is hosted by theNorwegian Microarray Consortium (NMC).

Core tasksTo conduct analyses. The platform has compiled jointgene probe collections for humans, rats and mice, andcan print microarrays from these as well as from othergene collections compiled by users. To provide databases and infrastructure for storageof information about the microarrays, for storage of allexperimental data, for simple data analysis andadvanced analysis of microarrayed gene expressiondata. For the most part, these services are availablewithout charge to users.To build competence through the operation ofnetworks for the exchange of expertise between micro-array users. To supply and further develop vitalexpertise in bioinformatics.To organise courses in microarray technology andadvanced microarray data analysis for researchers andtechnicians.To conduct research through participation in scientificprojects in cooperation with Norwegian and foreignresearch groups.

Microarray Technology

Diagnostics using microarrays Microarray analysis is being utilised to identify which breastcancer patients will need chemotherapy after surgery. Thus,women whose prognosis for survival is deemed just as goodwithout chemotherapy do not undergo unnecessary treatment.Microarray technology is helping scientists to develop betterdiagnostics for diseases such as cancer, and will contribute toearly disease detection as well as identification of the optimaltargeted treatment for the individual patient. This will increasesurvival rates and reduce the incidence of over-treatment.

The Technology Platforms

Photo: O. Myklebost, The Norwegian Radium Hospital

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Core tasksTo analyse, identify and characterise proteins and theirfunctions.To cooperate within the priority areas of post-

translational modification and protein-proteininteraction. The platform is also open to

cooperation with external projectswithin these areas.

To organise national coursesand workshops in proteomicsfor researchers. Courses areheld annually to demonstratetechnologies for variousforms of protein separations,for sample preparation formass spectrometry analysisand for carrying out mass

spectrometry on proteins.To provide guest facilities for

researchers visiting for shorter orlonger periods of time to enable

them to carry out their own projectsunder the supervision of platform

personnel.To conduct research through participation in scientificprojects in cooperation with Norwegian and foreignresearch groups.

OrganisationPROBE is based in the Building for Basic BiologicalResearch at the University of Bergen, and is co-financed by the university and FUGE.

ContactPlatform Coordinator:Research Fellow Kari Espolin Fladmark, Ph.D.,Department of Biomedicine, University of Bergen

E-mail: [email protected]: www.probe.uib.no

From thousands of genes to millions of proteins …The number of genes varies from organism to organism.No matter how many genes an organism has, however,there are far more products (proteins) produced than thenumber of genes would imply. This is becausethe gene codes can be read in differentways and the gene products arefurther processed within the cells.The approximately , genesdefined for humans give rise to amuch higher number ofdifferent proteins. Proteomicsresearch is aimed at identi-fying, quantifying anddefining the function ofproteins. Such protein studiesare likely to form the corner-stone of the diagnosticprocedures and individualisedmedical treatment of the future.Proteomics will also comprise a vitaltool for all types of basic biologicalresearch.

Main responsibilities and activitiesThe FUGE platform for proteomics is hosted by theNorwegian Proteomics Centre (PROBE), whichconsists of a service unit and a research unit. Theservice unit conducts protein analysis on samples ofbiological material from all of Norway, while theresearch unit carries out research to support PROBE’sservices. Research activities at PROBE are focused onprotein-protein interactions and post-translationalmodifications. In addition to its own researchers, theplatform hosts two positions for international scientists,both of which are filled by renowned researchers withspecial expertise in the centre’s priority areas andgeneral mass spectrometry analysis of proteins.

Proteomics

The Technology Platforms

Structural analysisIn mammals, enzymes are most active and stable at approxi-mately oC. The enzymes of organisms that live at lower orhigher temperatures function best at the organism’s core bodytemperature. The variation in enzymatic functions may be dueto differences in the enzyme’s structure, which can be studiedby generating three-dimensional images. Biotech PharmaconAS, located in Tromsø, Norway, has commercially produced anenzyme that functions best at low temperatures. The companyhas employed the expertise and methods available from thePlatform for Structural Biology in its search for greater under-standing of how different enzymes work.

Photo: P. E. Lillholm, PROBE

Ill.: NORSTRUCT

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Core tasks:To analyse protein samples, conduct crystallisationexperiments and carry out X-ray data collection testing.These are part of the free services offered by theCentre. The methods used to determine protein struc-ture will depend on the client’s needs, the complexityof the project and the available capacity. To conduct training and provide advisory services forproject participants from research groups throughNorway. The Centre will host and supervise visitingresearchers. The instrumentation in Tromsø and thedata collection equipment at SNBL may then be freelyutilised both to conduct individual projects and toenhance expertise. The Centre provides partial fundingfor research visits to Tromsø. To collaborate with external partners in need of full-scale structure determinations of proteins.To organise courses in structural biology and crystal-lography. To conduct research through participation in scientificprojects in cooperation with Norwegian and foreignresearch groups. The Centre’s internal projects will betargeted towards gaining new insight into the diseaseand disease-defence mechanisms of fish.

OrganisationNorStruct is organised under the Department ofChemistry at the University of Tromsø’s Faculty ofScience.

ContactPlatform Coordinator: Professor Arne O. Smalås,Norwegian Structural Biology Centre, University ofTromsø

E-mail: [email protected]: www.norstruct.uit.no

Form fits function…The three-dimensional structure (or shape) of biologicalmolecules determines their function within theorganism. In order to understand how they work, thesemolecules must be studied at the atomic level, and theirspatial structures must be visualised. Understanding therole that the different segments of the molecule play inits function will help scientists to uncover what cansometimes go wrong, for instance in the case of certaininherited diseases. Enhanced understanding of molecularstructure and function also has a wide range of practicalapplications, such as in the manufacture of biologicallyactive proteins (enzymes) that function optimally at lowtemperatures.

Main responsibilities and activitiesThe FUGE platform for structural biology is hosted atthe Norwegian Structural Biology Centre (NorStruct),which is responsible for providing infrastructure andexpertise in the 3D structure determination of biologi-cally active macromolecules through the use of X-raycrystallography. The platform is designed to serve as anational service and competence centre in structuralbiology. NorStruct will establish facilities and proce-dures for an effective “assembly-line” production ofbiologically active macromolecules for processing andanalysis with regard to their functions and three-dimensional structure. The platform will monitordevelopments in structural biology research by main-taining close contacts with top international researchestablishments in this field. NorStruct will providecutting-edge expertise that can be used to strengthenrelevant research projects throughout Norway.NorStruct is also responsible in practical terms forfollowing up the Swiss Norwegian Beamlines (SNBL)at the European Synchrotron Radiation Facility (ESRF)in Grenoble, France, as well as enabling Norwegianbiological researchers to make the best possible use ofthese facilities.

Structural Biology

The Technology Platforms

Photo: NORSTRUCT

Photo: NORSTRUCT

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Core tasksTo provide analysis and methodology in in situhybridisation; microdissection of cells and tissues;fluorescence protein studies such as fluorescencerecovery after photobleaching (FRAP), fluorescenceresonance energy transfer (FRET) and fluorescencelifetime imaging microscopy (FLIM); and magneticresonance imaging (MRI) of live experimental animals. To provide training and guidance to Norwegianresearch groups, who are entitled to visit the centre andwork under the supervision of platform personnel. To cooperate with Norwegian research groups.To organise courses for researchers and technicians.To conduct research through participation in scientificprojects in cooperation with Norwegian and foreignresearch groups.

OrganisationThe Molecular Imaging Centre has been established incooperation between the University of Bergen and theUniversity of Science and Technology in Trondheim.The University of Bergen is in charge of coordinationof activities.

ContactPlatform Coordinator: Associate Professor Anna Aragay,Department of Biomedicine, University of Bergen

E-mail: [email protected]: www.uib.no/med/avd/iac/mic/index.html

Images provide insight…How do genes and their products interact in living cellsand organisms? It is easiest to understand somethingthat can be seen with the naked eye. So the challenge inthis sphere is how to make visible that which is not onlyminute but also well hidden.Microscopy techniques have been in use for severalhundred years, but the recent rapid technologicaldevelopments in microscopy, laser technology, and dataand image processing have completely revolutionised thisfield. It is now possible to visualise structures andprocesses in living cells both three-dimensionally and intime (D). Molecular imaging shows how proteins andorganelles “move” inside and between living cells.Together with other microscopy and molecular biologytechniques, this will provide a better grasp of howmolecules and cells function in healthy as opposed to sickindividuals. This technology can be applied to single cellsand tissues as well as to living test animals.

Main responsibilities and activitiesThe platform for molecular imaging is responsible fordeveloping imaging technology and making equipmentand technological know-how accessible to research infields such as cellular and developmental biology,neurobiology and cancer research. This platform ishosted by the Molecular Imaging Centre (MIC), whichprovides the Norwegian research community withservices in advanced imaging technology. The MIC willoffer state-of-the-art equipment and expertise, andthere are long-term plans to establish a forum forresearchers employing various types of imagingtechnology.

Molecular Imaging

The Technology Platforms

An example of the use of molecular imaging technology(magnetic resonance) using manganese ions as markers.Here, nerve regeneration after injury to the centralnervous system is being studied.Photo: Christian Brekken, Department of Circulation and Medical Imaging, NTNU

Photo:The Molecular Imaging Centre

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Transgenic Mice

The Technology Platforms

Genes in different contexts …A variety of methods may be used to understand thefunctions of genes within an organism. For instance, it isuseful to compare individuals who possess certaindifferent traits. Such differences may be due to variationsbetween the genes that code for the same product andmay arise as a result of changes in the coding, known asmutations.The intestinal bacteria E.coli, yeast and fruit flies haveserved as the most important model organisms used tostudy genetic and molecular biological change. Genesfrom other organisms, such as humans, may also bestudied in model organisms. Today, transgenic micecomprise a vital model organism in molecular biology. Bybreeding mice that lack certain genes, termed “knockout”mice, it is often possible to find the explanation for howthe normal gene functions. Among other applications,transgenic knockout mice are used to study genesrelating to disease.

Main responsibilities and activitiesThe transgenic mice platform is responsible forproducing transgenic mice for Norwegian researchestablishments, and for assisting researchers workingwith transgenic mice. The platform will also provide avariety of other services associated with transgenicmice, such as embryo transfer, DNA testing andcryogenic embryo preservation. The platform is hostedby the Norwegian Transgenic Centre. The Centre willmaintain a stock of vectors and a DNA library for usein transgenic studies. In addition, the Centre offersanimal care facilities.All new projects must receive official approval fromthe authorities.Research communities using the Centre are responsiblefor breeding their own transgenic mice.

Core tasksTo produce knockout mice through cultivation andgene manipulation of embryonic stem cells and mouseblastocyst injections.To produce conventional transgenic mice by means ofDNA injections in fertilised eggs.To provide courses for researchers and technicians.

OrganisationThe Norwegian Transgenic Centre is organised underthe Faculty of Medicine at the University of Oslo. TheCentre is located at the National Hospital of Norway,which features the country’s most modern animalfacility.

ContactPlatform Coordinator:Research fellow Christian Johannes van den Bout,Department of Comparative Medicine, NationalHospital of Norway

E-mail: [email protected] Website: dna.uio.no/ntc

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Core tasksTo build competence bystrengthening ongoingprojects in microbialgenome research andintegrating functionalgenomics into microbialscience research.To build up necessaryinfrastructure. To conduct researchthrough participation in scientific projects in coopera-tion with Norwegian and foreign research groups. Themost important research areas include: • Horizontal gene transfer, genome maintenance and

studies of type IV pili in Neisseria meningitidis.• Comparative genome studies (chromosomes,

plasmids and phages) of the bacteria group Bacillus cereus.

• Horizontal gene transfer between streptococci. • RNA-genes in DNA dynamics and microbial stress

response. • Molecular biology of DNA replication and

coordination with the cell cycle.

OrganisationCAMST is comprised of six research groups with thefollowing coordinators:Professor Michael Koomey, The Biotechnology Centre of Oslo, University of OsloProfessor Anne-Brit Kolstø, The Biotechnology Centre of Oslo, University of OsloProfessor L. Sigve Håvarstein, Agricultural University of Norway, ÅsProfessor Erling Seeberg, National Hospital of Norway, University of OsloProfessor Tone Tønjum, National Hospital of Norway, University of OsloProfessor Kirsten Skarstad, The Norwegian Radium Hospital, University of Oslo

ContactPlatform Coordinator:Professor Michael Koomey, The Biotechnology Centre of Oslo, University of Oslo

E-mail: [email protected]:www.biotek.uio.no/research.koomey/index.htm

Tiny organisms with a big impact…Bacteria play a major role in many areas of human life,and carry positive and negative impacts for health anddisease, for food production and other commercialactivities, and for nature and the environment. Thus,knowledge and understanding of bacteria is crucial toadvancements in industry and health. Basic research inmicrobiology is called for, and Norwegian researchgroups need access to the expertise and equipmentrequired for microbiological research. Basic microbiologyresearch is also important for promoting the develop-ment of commercial products.

Main responsibilities and activitiesThe FUGE platform for basic microbiology is based onthe use of bacteria as genetic model organisms.Together with related advanced technologies, functionalgenomics may serve to revolutionise research in micro-biology. However, strategies to maintain and encouragesuch research are needed if we are to successfullyutilise Norwegian opportunities in this area. Themicrobial science platform is responsible for providingexpertise, training and access to equipment andfacilities for interested groups and individuals in thesefields. Activities will include organising courses,conferences and meetings for Norwegian researchgroups as well as seminars with top-level internationalresearchers. The platform is hosted by the Consortiumfor Advanced Microbial Sciences and Technologies(CAMST).

Microbial Science

The Technology Platforms

Microbiology GENPOINT, a Norwegian company, develops and markets diagnostic kits utilizing its proprietary DNA-based technology for fast and easydetection of pathogenic and toxic microorganisms. With GENPOINT’stechnology a wide range of bacteria and other microorganisms can beisolated from a broad spectrum of samples. It is also possible toidentify several different strains and species simultaneously.

Photo: Novozymes, Denmark

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Core tasksTo provide analysis services in transcriptionalprofiling (cDNA- and oligonucleotide-based DNAmicroarrays), protein interactions (yeast two-hybridanalysis), and expression analyses (in situ hybridi-sation). In addition, services involving clone collection,transformation and formation will be made available. To build national competence in plant functionalgenomics. The platform is designed to increasepractical know-how in functional genomics and large-scale analyses. To cooperate in Norwegian and international researchprojects. The platform will work to strengthencooperation between national and international researchgroups. To organise courses for researchers and technicians.To conduct research through participation in scientificprojects in cooperation with Norwegian and foreignresearch groups.

OrganisationThe platform is coordinated from the University ofScience and Technology in Trondheim, and is acollaborative effort that includes the University of Osloand the Agricultural University of Norway (NLH) in Ås.

ContactPlatform Coordinator: Professor Atle M. Bones,Department of Biology, Norwegian University of Scienceand Technology, Trondheim

E-mail: [email protected]:www.boneslab.chembio.ntnu.no/NARC/Narc.htm

Plant Functional Genomics Human civilisation is based on effective agriculture.Virtually all food for human and animal consumptioncomes from cultivated crops. In the future, aquacultureproducts may also be dependent on plant-based feed.Moreover, plants provide wood and fibre that may beused for paper and clothing, as well as bioactivecompounds utilised in many medicines. Production ofplants and plant products is the world’s largest industry.Plant functional genomics will facilitate the productionof healthier plants that provide a larger volume of higherquality, more nutritious foodstuffs.

Main responsibilities and activitiesThe platform for Plant Functional Genomics has beenestablished for large-scale plant-based functionalgenomic analyses. The platform is run under theauspices of the Norwegian Arabidopsis ResearchCentre (NARC). Activities are largely directed towardsresearch on the flowering weed Arabadopsis thaliana,which is used as a model system for plant biology byresearchers worldwide. Many of the findings associatedwith Arabadopsis thaliana can be applied directly toother plant species, including those comprisingcommercially important crops. NARC is responsible forproviding a national competence and service centre forNorwegian researchers and research groups, and willwork to promote enhanced activity in the field of plantfunctional genomics.

Plant Functional Genomics

The Technology Platforms

Photo: R. Aalen, The Plant Genomics Centre, Univ. of Oslo

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FUGE’s administrationAddressResearch Council of NorwayP. O. Box St. Hanshaugen,NO- OsloNORWAYTelephone: + , Telefax: + E-mail: [email protected] Website: www.rcn.no, www.fuge.no

SecretariatSteinar BergsethCoordinatorTelephone: + E-mail: [email protected]

Randi AamodtRandi AamodtAdvisorTelephone: + E-mail: [email protected]

Marit BjørkanSecretaryTelephone: + E-mail: [email protected]

FUGE’s BoardChair Professor Ole Petter OttersenCentre for Molecular Biology and NeuroscienceUniversity of OsloE-mail: [email protected]

MembersProfessor Anne-Lise Børresen-DaleDepartment of GeneticsNorwegian Radium Hospital, Oslo E-mail: [email protected]

Director Geir Gogstad Genpoint AS, Oslo E-mail: [email protected]

Professor Ole-Jan IversenFaculty of Medicine, Medical Technology Centre,Norwegian University of Science and Technology,Trondheim E-mail: [email protected]

Associate Professor Jorunn B. JørgensenNorwegian School of FisheriesUniversity of TromsøE-mail: [email protected]

Research Director Lene LangeNovozymes AS, Denmark E-mail: [email protected]

Professor Vidar M. SteenCentre for Medical Genetics and MolecularMedicine, Haukeland University HospitalE-mail: [email protected]

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