Mid-Size Instrumentation in the Life Sciences: IV. Advanced Light Microscopy Imprint ERA-Instruments Christian Renner Achim Tieftrunk Deutsche Forschungsgemeinschaft (DFG) Kennedyallee 40 53175 Bonn [email protected] [email protected] Euro-BioImaging Jan Ellenberg European Molecular Biology Laboratory (EMBL) Meyerhofstr. 1 69117 Heidelberg [email protected] Layout Bosse und Meinhard GbR, Wissenschaftskommunikation Images Cover: Tomoya Kitajima, Ellenberg group, EMBL 6, 18: istockphoto 12, 16: Advanced Light Microscopy Facility at EMBL Heidelberg Print Brandt GmbH, Druckerei und Verlag More information on www.era-instruments.eu and www.eurobioimaging.eu Mid-Size Instrumentation in the Life Sciences: IV.Advanced Light Microscopy 3 Content 4 Preface........................................................................................................... 5 Summary....................................................................................................... 6 AdvancedLightMicroscopy(ALM).................................................................. 7 ALMcentres................................................................................................... 8 Fundingschemes........................................................................................... 13 UserForums................................................................................................... 15 CoreFacilityUserFees.................................................................................... 16 Innovation..................................................................................................... 17 Software......................................................................................................... 19 DataChallenge............................................................................................... 21 TechnologyOutlook........................................................................................ 22 Conclusions.................................................................................................... 23 AboutEuro-BioImaging................................................................................... 24 AboutERA-Instruments................................................................................... 26 Preface ThethreepreviousissuesoftheERA-Instrumentsseries“MidsizeinstrumentationintheLifeSciences”haveaddressed generalaspectsoflifescienceinstrumentation1.Thisfourth publicationnowfocusesspecificallyononefieldandtransformsthemoregeneralremarksandconclusionsofthepreviouspublicationsintospecificrecommendations. ModernlightmicroscopywithitsexcitingandrapiddevelopmentshasbeenamajorthemethroughouttheERA-Instrumentsdiscussionsandadedicatedusermeetingonlaserbased microscopywasoneofthefirstactionsofERA-Instruments.At thesametimethistopicwasputontheESFRIroadmap2inthe frameofEuro-BioImaging. Euro-BioImagingisalarge-scalepan-Europeanresearch infrastructureprojectinthefieldofbiologicalandbiomedicalimaging.Itsmissionistoprovideaclearpathofaccessto acompleterangeofessentialimagingtechnologiesforevery biologistandbiomedicalscientistinEurope.Euro-BioImagingis ontheESFRIRoadmapsince2008andthepreparatoryphase projectwithfinancialsupportfromtheEuropeanCommission hasbegunin2010. ThescopeofEuro-BioImagingencompassestheissuesoflight microscopythatERA-Instrumentshastoucheduponand,thus, itseemsfittopresentherejointlyresultsandrecommendations.WhileERA-Instrumentsaddressesabroaderrangeof instrumentation,Euro-BioImagingisthededicatedresearch infrastructureprojectforbiomedicalimagingandtheforum fordevelopingdedicatedaccesspolicies,financialmodelsand moreforthisfield. 1See:http://www.era-instruments.eu/what_we_do/publications.html 2ESFRI,theEuropeanStrategyForumonResearchInfrastructures: (http://ec.europa.eu/research/infrastructures/) 5 Summary Lightmicroscopyhasrecentlyseenanincredibleboost intechnologyandmethodsdevelopment.Thedegree ofsophisticationoftheinstrumentationisoftensuch thatspecializedexpertiseisrequiredforefficientand successfuloperationaswellasforproductiveuseofthe resultingimagedata.Ithasbecomenotonlyinefficient,butimpossiblethateveryuseroflightmicroscopy mayacquirein-depthexperiencewithallthediverse techniquesthathavebecomeavailable.Consequently, corefacilitiesareinstalledforpoolinginstrumentation aswellasexpertise.Thesemicroscopyfacilitiesprovide state-of-the-arttechnologiesandmethodsforabroad rangeofscientificusers.Theycanalsoactasalink betweenvarioususergroups,thetechnologyoriented developersandthecommercialinstrumentproviders. Sufficientfunding,notonlyforinstrumentation,but alsoforexpertpersonnel,maintenance,upgradesetc. hastobeprovidedtothecorefacilitiesallowingthem toprovidehighqualityscientificservicetousers,includingexternaluserswheneverpossible.Userfeesforacademicuserswilltypicallycoversomerunningcosts,but fullcostscanonlybechargedtousersfromindustry. Researchgrantshavetoallowfortheseuserfees. Matureinstrumentationshouldnormallybeintegrated insuchcorefacilities,whereasdedicatedorspecialized microscopeswillstillberunbyindividualexpertgroups. Developmentofnewtechnologiesismostlydoneinthe laboratoriesofphysicistsorengineers.Theycanalso benefitfromlinkstothecorefacilitythatcanprovide atestinggroundfornewdevelopmentsorprototypes 6 andcanconveytheexpectationsofthebiologicaluser community.Thecommunicationbetweendevelopers andbiomedicalresearchersshouldbefostered,sothat methodsdevelopmentisacceptedasintegralpartof lifescienceresearchwhilethedevelopersshouldbe awareofthebiologicallyrelevantquestions. Afundinggapisidentifiedatthetransitionfromanew developmenttoacommercialprototype:Themarket potentialthatisaprerequisitefortheengagementof acompanycanhardlybetestedwithonlytheoriginal set-upattheopticalbenchoftheinventorordeveloper. Duplicatesneedtobeprovidedtotheusercommunity andtestedfortheirusefulnessregardingbiological questions,ideallyincooperationwithacorefacility.A lackoffundingfortheseduplicatescanblocktheinnovationpipelineatthispoint. ITinfrastructureandbioinformaticsshouldbeseen asintegralpartsofadvancedmicroscopyfacilitiesor platformsandneedtobeincludedalsoinearlystages ofplanning.Sufficienthumanandfinancialresources needtobeprovidedtomeetthedatachallenge. Interoperablesoftwaretoolsandstandardizeddataformatsarerequiredtotransformthelaboriouslyacquired imagedataintoscientificallyvaluableresults.Funding organisationsshouldpromoteandsupportopensource developmentsthatareincreasinglyrecognizedalsoby thecompanies. Advanced Light Microscopy (ALM) LightMicroscopyhassincethebeginningofmodern scienceprovidedinsightsintothemysteriesoflife.The structureofbiologicaltissue,theveryexistenceoflivingcellsandtheircomponentsareonlyknowndueto thistrulyindispensableinstrumentation.Thestandard microscopeprovidingnotmorethanilluminationof thesampleandmagnificationoftheopticalimageis stillanextremelywidespreadandusefultool.However, duringthelastfewdecades,technologydevelopment hasmovedmodernlightmicroscopytoutterlynew dimensions–inthetruesenseofthesewords.Laser scanningmicroscopeshaveincreasedresolution,but moreimportantlytheyhavemadeaccessiblethethird spatialdimensionprovidingstacksofimagesinsteadof asingleprojectionimage.Thetemporalandspectral resolutionprovidesadditionaldimensionsthatthese microscopesallowexploring. Inrecentyearsabroadvarietyofnewmethodshave beendevelopedtofurtherextendthepossibilitiesof advancedlightmicroscopy(ALM),intoeverincreasing temporalandspatialresolution,molecularspecificity andhigherthroughput.Observationofsinglebiomoleculesandsub-wavelengthresolutionareonlytwo impressiveexamplesofwhatcanbeachieved. Alongthisdevelopmentoftechnology,instrumentation hasbecomeobviouslymoreandmoresophisticated and,nosurprise,moreexpensive.Besidestheinvestmentcostsforpiecesofequipment,itisalsoincreasinglyimportanttoinvestinexpertiseandsurrounding infrastructure,especiallyappropriatecomputational andITsupport,forexploringthepossibilitiesthatthe technologycanprovide.Ithasbecomeinefficient,ifnot impossible,foreveryscientistthatreliesonALMtoown andoperatetheequipmentallbyhim-orherself.The foundingofcoreunitsandservicegroupsisparalleling andsometimespioneeringthedevelopmentinother areasofoperatinglifescienceinstrumentationincore facilities.3 3SeeERA-InstrumentsrecommendationsIII:„Developmentof researchinfrastructuresinEurope“ 7 ALM centres Core facilities providing access to state-of-the-art technology Inthescientificcommunityaclearpreferenceforand tendencytowardsfoundingcentresorcorefacilitiesis recognizable,whichis,however,onlypartiallyreflected bythecurrentsituation.Similartootherkindsoflife scienceinstrumentationitisnotalwaysusefultoincorporateallmicroscopesintocorefacilities.Onemay distinguishdifferentkindsofALMinstrumentation,for instance,basedonthematurityoftheset-up: • CommerciallyavailableALMequipmentthatshould berunincorefacilities, • Dedicatedcommercialmicroscopesthatareused tocapacitybyindividualresearchgroups,butare sometimesmaintainedbycorefacilities, • Testinstrumentsandprototypesthatareoperatedin demoareasofcorefacilitiesorthespecialist’slab, • Opticalbenchesandbreadboardinstrumentsor techniquesthatarestillunderdevelopmentbyspecializedgroupsintheirownlabs. Thesecategoriesarenottotallyclear-cutandthereis activediscussionamongthescientiststowhichextent thisdifferentiationishelpfulornecessary.Amajorconcernisthecompetitionfor(thesame)funds.Nevertheless,majordifferencesexistbetweenthesecategories andrequirementsaretosomedegreedifferent. 8 Whycorefacilities? Corefacilitiesaretypicallyserviceunits,whosemissionistoprovidestate-of-the-artinstrumentationto apotentiallylargenumberofscientiststhatuseALM techniques,butdonotown,operateandmaintain therequiredinstrumentsthemselves.Thedrivingforce forcreatingcentralcorefacilitiesisoftenthatnotall researcherswhoareinneedofALMusetheinstrumentstofullcapacity,and/orhavethefinancialmeans and/orexpertisetooperatetheirowninstrumentsat fullpotential.Therefore,thedegreeofcapacityutilizationandtheefficiencyofoperationareusuallyhigher foracorefacilitycomparedtoindividuallyrunequipment.Poolingofindividualfundsforlargerinvestments inacentralfacilityshouldbeencouragedandtypically alsoenablestheinstrumentstobeupgradedtokeep themstate-of-the-artmorefrequentlythaninindividual researchgroups. Goodservicerequiresexperts! Akeyadvantageofcorefacilitiesisthathigh-level expertiseofthescientificandtechnicalstaffcanbe maintainedlong-term,whichisdifficultinindividual researchgroupswhereexpertisecanfluctuateontime scalesshorterthaninstrumentlifetimes.However, identifyingandprovidinganattractiveemployment environmentfortherequiredhighlyqualifiedpersonnel, especiallyinstrumentationscientistsandengineers,for corefacilitiesisverydifficult,becausetheavailablepositions,salariesandcontractconditionsaredesignedfor shorttermscientificstaffsuchaspre-andpostdoctoral fellows,orstaffwithlowerleveltechnicalqualifications suchasresearchtechnicians.Toattracthighlyqualified personnelandmaintaintheirexpertiseatthecutting edgeofthefield,corefacilitystaffshouldbeemployed withpermanentpositionsor,atleast,a>5yearsperspective. calprocess.Datahandling,storing,andcompression thusrequiresanappropriateIT-infrastructureandcan beautomatedtoacertainextentincorefacilitieswith appropriatedatabasesandlaboratoryinformation managementsystems(LIMS)tailoredtoimagingcore facilities.Nevertheless,usersfrequentlyneedtraining onhowtoobjectivelyscoretheirdatamanuallyorhow tousecomputationalimageanalysistoolstoextractthe desiredparametersfromtheimagesautomatically. Broadusersupportandtraining. Technologydevelopmentincorefacilities. Acorefacilitynotonlyprovidesaccesstostate-of-theartinstruments,butalsoscientificandtechnicalsupport aswellastrainingtailoredtotheindividualexpertise andscientificneedsoftheuser.Samplepreparation isacrucialstepforsuccessfulmicroscopyandmust beincludedintheservicesofcorefacilities.Advanced microscopyaccessshouldbeaccompaniedbyteaching coursesinmicroscopy.Educatinguserstypicallyleads tohigherqualityscientificresultsandcanalleviatethe recurringproblemthatusersaredifficulttosatisfywith lessthanthemostadvancedinstrumentation,regardlessoftheactualrequirementsoftheresearchquestion athand.Advisingusersinthechoiceoftheinstrument andthespecifictechniquetobeusedisanimportant taskoffacilitystaff.Finally,imaginginstrumentsproduceincreasingamountsofdigitalimagedata,whose valueoftenliesinquantitatingtheobservedbiologi- Becauseoftheirbroaduserrange,corefacilitiestypicallyexperiencethelimitationsofcommercialinstrumentationinsatisfyingresearchdemandsveryearly.They arethereforeinanexcellentpositiontodevelopnew imagingapplicationsandimprovementsincommercial instrumentationhard-orsoftwareinordertomeetthe researchdemands.Thisistypicallyrealizedincollaborationwithindustrialpartnersthatbuildtheinstruments. Forindustry,corefacilitiesareimportant“application scouts”andattractivedevelopmentpartners,because newinstrumentsandprototypescanbesubjected totestingandtrouble-shootingwithuserswhohave suitableresearchapplications.Thistechnologydevelopmentistypicallyincrementalandbasedoncommercial orclosetocommercialtechnology,ratherthanfundamentallynewconceptsinoptics. 9 Dedicated Instruments for individual research groups Evaluationofcorefacilities. Thescientificsuccessofresearchgroupsistypically measuredbypeerreviewedpublications.Sincethe missionofcorefacilitiesistosupportresearch,their evaluationshouldbebasedonthesciencetheyenable, whichmayonlybeevidencedbyacknowledgments inpublicationsorthedegreeofusageandthequality andproductivityoftheusers.Astandardizedadequate evaluationandrewardsystemforcorefacilitiesand theirstaffneedstobedeveloped,whichisoneofthe goalsofEuro-BioImaging. Aninterestingconceptisthedefinitionofa“corefacilitycertificate”toassureminimalqualitystandardsfor theseserviceunits.Thecriteriaforsuchacertificate shouldbedefinedbythebiologicalimagingcommunity,preferablyattheEuropeanlevel,whichisoneof thegoalsofEuro-BioImaging.Itshouldbuildonexisting basicrequirementsdefinedforallresearchinfrastructures4. OpenAccessforsmallerinstitutionsandresearchers fromotherdisciplines. Runningacentralmicroscopyfacilityisdifficultforsmaller institutionsorthoselessfocussedonthiskindofresearch orcomingfromotherdisciplines,duetotheconsiderable totalcostsofoperationincludinginstrumentation,maintenanceandupgradesandpersonnel.Theseinstitutions wouldbenefitstronglyfromopeningexistingcorefacilities toexternalusersunderstandardizedopenaccessmodalitiesastheyarecurrentlydevelopedbyEuro-BioImaging. 4E.g.the„BasicrequirementsforallRIswithsharedaccess“ bytheEuroHORCs 10 Itiscrucialforresearchgroupsfocusedonimagingapproachesandapplicationstorundedicatedmicroscopes fortheirresearch.Thesesystemsaresotailoredtothe specificresearchapplicationsofthegroupand/orused tofullcapacitythatsharingtheinstrumentswithother usersisnotanoption.Also,bio-safetyrequirements forworkwithpathogensorradioactivesubstances maylimitsharedaccesstosimilarusers.Therefore,itis vitalthatsuchresearchgroupscontinuetobeableto runtheirownequipmentoutsideofcorefacilitiesand continuetoreceivefullfundingsupportforindividual instrumentation. Itshouldbenoted,however,thatitmaybebeneficial evenforhighcapacityandexpertresearchgroupstoassociatetheirdedicatedinstrumentswithcorefacilities, totakeadvantageoftheprofessionalinstrumentmaintenanceandconsultationininstrumentconfiguration aswellastrainingofnewmembersoftheirresearch groupbyexpertcorefacilitystaff.Thisappliesalsoto highbiosafety/radioactivityaccess,whichrequirescostly buildinginfrastructureandthereforebenefitsfrom poolingseveralinstrumentstoallowtakingfulladvantageofdifferentimagingtechnologies. FundingprogrammesforALMinstrumentationshould thereforebeopentocorefacilitiesaswellasindividual researchgroupsoperatinginstruments,butitmaybe usefultohaveseparatebudgets,fundingstreamsand evaluationcriteria,forthedifferenttypesofapplications.Closecommunicationofthefundingagencies withtheinfrastructureprovidersasiscurrentlybeingorganizedinEuro-BioImagingisanopportunitytoensure thatappropriatesystemsareputinplace. New technology for biological applications in developer labs Fundamentally new optical instruments in physics or engineering groups Theexpandingneedsofimaginginlifescienceresearch haveledtoanewgenerationoftechnologydevelopersthatassembleanddevelophighlycustomizedor newnon-commercialinstrumentsforspecificbiological questions.Complicatedexperimentswithsuchspecializedhome-builtinstrumentationonopticalbenchesare oftennotpossibleincorefacilities,becausethetechnologyisnotsufficientlyrobustormaturetoofferit toabroaduserbase.Onceatechnologyhasbeendemonstratedasappropriateforabiologicalapplication, demandforitoftenincreasesbeyondthedeveloping groupanditsdirectcollaborators.Tofacilitateaccess toabroaderuserbase,itisnecessarytoprovidefunds forduplicatingsuchprototypeswithinprojectfunding schemesbeforethetechnologyiscommerciallyavailable.Earlyaccesstoalargerusergrouphelpstoevaluate thegeneralutilityofnewinstrumentsandtechnologies quicklyandsupportsmoreresearcherswithnewtools morequickly. Developmentoffundamentallynewinstrumentsbased onnewopticalconceptscannotbedoneincorefacilitieswithindustrialpartnersandoftennotevenby developerswhotargetdefinedbiologicalapplications. Suchtechnologiesareoftendevelopedinthephysicist’s oropticalengineer’slabwithoutbiologicalapplications inmindanddevelopersmayhavenoreasontoprovideanewtechnologytobiologists.Developmentsin optics,especiallyinmicroscopyhardwareandsoftware, eventuallywillhavemajorimpactsinbiology,butthe developmentofnovelconceptscantakemanyyears andsometimesdecadesbeforethisimpacthappens. Onceabroaderuserinterestbecomesclearandthe robustnessofthetechnologyhasbeenimprovedinthe courseofaccessprovision,itcanbegraduallymoved intoacorefacility,forcompletelyopenaccess.Thiswill typicallygoalongwithastrategyforcommercialization,forwhichastrongcasecanbemadeatthispoint. Thus,bothdeveloperlabsandcorefacilitiesbenefit fromcloseassociationtoalloweasyandfrequentcommunicationandaclearpipelineforgradualtransferof newinstrumentsandtechnologiesintocorefacilities thatmaygoalongwithandfacilitatecommercialization. Thus,thecommunitiesdevelopingnewtechnologyand thoseapplyingittorelevantbiologicalquestionsare ratherseparateand,importantly,therewardsystems aredifferent,i.e.differentjournalsandconferences thatareconsideredimportantforpublishingresults. Acknowledgingthatmethodsandinstrumentationdevelopmentisafoundationandintegralpartofexperimentallifescienceresearchisveryimportant.Onthe otherhand,everynewALMtechnologyhastoproveits usefulnesstoanswerimportantbiologicalapplications– alwaysincompetitionwithexistingtechniques.Novelty aloneisnotsufficient. 11 12 Tobridgethegapbetweenpureinstrumentdevelopers andpotentialbiologicalusers,regularmeetingsofthe biologicalimagingcommunitiesanddevelopersinthe physicsandengineeringcommunitieswouldbehighly beneficial. Thiswouldaidearlyevaluationoffundamentallynew imagingtechnologyconceptsfortheirpotentialinbiologicalapplications.Again,anassociationofdevelopers withimaginginfrastructureproviderscouldbeusefulto promoteawarenessofthebiologicalneedsonthedevelopers’sideandawarenessofnoveltechnologiesand theirpowerandlimitationsonthebiologicaluserside. Recommendations: Insummary,toprovideforthemanifoldALMinstrumentationneedsinthelifesciencesthereshouldbe corefacilitieswithstate-of-the-artcommercialequipmentandtotestanddeveloppre-commercialprototypeswithindustrialpartners,individualgroupswith dedicatedinstrumentsanddeveloperlabsforresearchingnewtechnologiesforspecificbiologicalapplications.Theselevelsbenefitfromcloseassociationand aclearpipelinefromdevelopmentvialimitedaccess toopenaccessandcommercialization.Anongoing exchangeofbiologicalusersanddeveloperswithphysicistsandopticalengineersthatdevelopfundamentally newtechnologyconceptswillensurethatnewtechnologiesmeetpotentialbiologicalapplicationsasearly aspossible. • Corefacilitiesshouldprovideopenaccesstoexternalusersfrominstitutionsthatcannotestablishtheir ownfacilitiesorlackcertaintechnologies. • State-of-the-artcommercialALMinstrumentation shouldpreferablybeprovidedbycorefacilities. • Corefacilitystaffneedsmidtolongtermemploymentperspectivesandtrainingcareerandevaluationsystemsadaptedtotheirspecialrequirements ashighlevelservicestaff. • Corefacilitiesshouldobtaintherequiredpersonnel andfundstobroadlysupportandtraintheirusers andthusprovidethebestpossibleservice. • LimitedaccesstonewlydevelopedALMtechnologiesinorfromdeveloperlabsshouldbesupported byfundingorganizationsviaduplicationofhomebuiltinstrumentsandprovisionofexpertstaff. • Fundamentalnewmethodsdevelopmentshould beacceptedasintegralpartoflifescienceresearch andthegapbetweenbiologicalusersandpure instrumentdevelopersshouldbebridgedbyregular meetings. Funding schemes Funding of core facilities Duetothekeyenablingroleoutlinedabove,suitable fundingschemesforcorefacilitiesbasedonthescience theyenable-documentedbyusernumbers,acknowledgementinscientificpublicationsanduserlettersof support-areneeded.Theseprogrammesshouldallow fundingofnewinstruments,necessaryupgradesand replacementstokeepheavilyusedinstrumentsstateof-the-art,aswellasmaintenanceofinstruments.They shouldalsoprovidefornecessaryITandbuildinginfrastructure,especially,whennewcorefacilitiesareestablishedbutalsowhenexistingonesundergoupgrades. Asoutlinedabove,keytothesuccessandaddedvalue ofcorefacilitiesishighlytrainedexpertstafftosupportandtrainusers.Thefundingschemesshouldallow personnelandrunningcostsaseligiblecostitems.It isimportanttogivethishighlycompetedforstaffmediumtolongtermcareertrackoptions.Jobsecurityand thedefinitionofatailoredevaluationsystemoftheir performancebythesciencetheyenableareneeded. Acentralaspectistheappreciationofsuchinstrument scientistsbytheresearchcommunity.Itcanbehelpfultospearheadthisnewtypeofpositionbystartup-fundingthroughresearchcouncilstoencourage theestablishmentofcorefacilitiesatuniversitiesand researchinstitutions.Dependingonthelevelofinstitutionalfundingthatthecorefacilitiesreceive,project grantstousersneedtohaveprovisionsforaccessfees tocorefacilities,whichcanincludetravelandlodgingofusersaswellastheactualinstrumenttimeand consumablecostofthecorefacility.Sinceopeningcore facilitiestoexternaluserswouldbeverybeneficialfor smallerinstitutionsandscientistsfromotherdisciplines, fundingtoincreasecapacitytosupportexternalusers shouldbemadeavailable. 13 14 Funding of individual instrumentation Funding of technology developments Intheexperienceofthescientistsfundingofstandard equipmentisoftendifficultalthoughrequiredfora broadusercommunity.Thefinancingofupgradesis complicatedcomparedtonewinstrumentationalthoughlesscostly.Fundingforexpensivecutting-edge instrumentationisofteneasiertoobtainthanformore modestandadequateequipment.Itisafrequentbut erroneousassumptionthatthemostexpensiveandsophisticatedinstrumentationwillmoreorlessautomaticallyproducethebiologicallymostrelevantresult. Technologicaldevelopmentsforbiologicalapplications shouldnotalwaysbeseenasanengineeringproblem, asitisoftennotacceptedinengineeringas“proper” engineering,butconsideredmereapplicationofknown principles.Applyingknownprinciplestonewapplicationsisoftenveryfruitful,butjustasoftennotacknowledgedforitsworth.Developmentofmicroscopy techniquesshouldbeacceptedasvalidandvaluable researchpreferablybothinthelifesciencesaswellas physicsandengineering. Evaluationofindividualinstrumentfundingapplications shouldbebasedonscientificneedsfordedicatedinstrumentsand,ifpossible,demonstrationofexperience andexpertiseinthespecificALMtechnologywithout puttingjuniorgroupsatadisadvantageinthecompetitionforfunds. Thereisafundinggapfeltbetweenopticalbenchesor prototypesandcommercialproductdevelopment,especiallywhenthepotentialmarketisstillundefined.Core facilitiesmayplayakeyroletotestthemarketpotential ofnewtechnologieswithmanyusersandincollaborationwithindustryprovidinganinstructiveexamplehow tobridgethisinnovationgap.Fundingschemesneed tosupportthiscriticalphase.Proprietarysoftwareand hardwareleadtoreinventing.Fundingorganisations shouldenforceandsupportopenacademicaccessto hardwareandsoftware.AdequateIPprotectionfor commercialuseisaprerequisiteforsuccessfulcollaborationwithindustry. User Forums Recommendations: • Adequatefundingschemesforcorefacilityinstrumentation,buildingandITinfrastructureandexpert staffareneeded. • Increasingthecapacityofexistingcorefacilitiesfor providingaccesstoexternalusersshouldbesupported. • Projectfundingschemesshouldallowtheinclusion ofuserfeesinprojectproposalsunlesscorefacilities receiveinstitutionalfundingforofferingexternal access. • Fundingoftechnologicaldevelopmentsinboth softwareandhardwareshouldbesupportedwithin biologicalprojectswithaclearcommitmenttothe newmethodology. Theprocessofpurchasingnewinstrumentscanbe verylong,becauseoflackofexperience.Twomeasures couldimprovethis.Firstofallcorefacilitiescanprovide anidealtestsiteforseveralstate-of-the-artinstrumentsfromdifferentmanufacturerssidebysideforthe specificapplication.Second,exchangeofexperience withnewinstrumentsandcoordinationofacademic customerscanbeveryuseful:Whatwentwrong?What wasgood?Whatproblemsappearedwiththenewinstrument?Usermeetingsindifferenttechnologyareas, suchasprovidedwithintheannualELMImeetings5 alsoservethispurpose.Finally,inordertocreatemore transparencyitwouldbedesirabletodisclosepublicly financedinvestmentsaswellascompanies’offers. 5Seewww.embl.org/elmi/ • Fundingschemesfordedicatedstandardorcuttingedgeinstrumentationforsingleinvestigatorsmust exist,butshouldbeseparate,preferablywitheven separatedbudgets. • Fundingorganisationsshouldfollowuponcommitmentsregardingrunningcoststhataregivenwhen universitiesapplyforinstrumentationorcollaborativeresearchcentres(thatdependoninstrumentation). 15 Core Facility User Fees Inmicroscopyfacilitiestheattitudetowardsuserfeesis verysimilartothatinlifesciencesingeneral.6Neither fullcostsnorfreeaccessareconsideredidealsolutions.Experienceshowsthathighorfullcostuserfees discourageusersthathaveonlylimitedmeanstopay fromtheirownbudget,whichputsespeciallyjunior investigatorsatanundesirabledisadvantage.Inaddition,highuserfeesmisleadscientistsintoapplyingand, potentially,purchasingtheirowninstruments,evenif theydonotuseittofullcapacityandlackthenecessary technologicalexpertise.Afullcostmodelthatincludes instruments,staffandallrunningcostsofthecore facilitiesisthereforenotpracticalforacademicusers. However,fullcostsarecommonlychargedtocommercialusersfromcompanies.Whiletheyusuallyconstitute onlyasmallfractionoftheusers,thegeneratedincome canbeflexiblyusedtocontributetomaintenanceand upgradecostofthecorefacility. Moderateuserfees,basedontheconsumablebut notthestaffnortheinstrumentationcostofthecore facility,increasecommitmentandefficiencyintheuse ofthemeasurementtime.Suchfeescanbegraduated dependingontheservicesused,suchassamplepreparation,reconfigurationofimagingequipment,data storage,analysisandevaluation. 6See,forexample,thefirstissue“EfficientOperationand Access”ofthisrecommendationsseries 16 Externalusersfromotheruniversitiesorinstitutionsare usuallychargedhigherfeesthanlocalusersconsistent withthefactthatlocalcorefundingusuallycoversa largefractionofthetotaloperatingcosts. Userfeesshouldbecomparableforsimilartechniques andinstrumentsatleastatanationallevel(dependingonnationalfundingsituations)andideallyacross Europe,agoaltowardswhichthestandardizationinitiativeofuseraccessmodalitiesinEuro-BioImagingisactivelyworkingtowards.Thereisacertainconvergence onhourlycostsforprovidingminimumorfullsupport tousersofAdvancedLightMicroscopy,basedonpracticalexperienceoftheleadingEuropeancorefacilities thatcanserveasamodel.Theuseofnon-commercial newlydevelopedequipmentshouldremainfreeof chargetotheuserandisusuallybasedonscientificcollaborationsratherthanservicecontracts,butdeveloper groupsshouldbegivenadditionalfundingsupportto providethesemethodstoabroaderuserbaseearly, beforetheyreachsufficientmaturityforinclusioninto corefacilitiesand/orcommercialization. Innovation Recommendations • Consideringthatfundsforinvestmentsareusually easiertoobtainthanrunningandmaintenance costs,manufacturersshouldbeaskedtobuild standardinstrumentationevenmorerobust. • Userfeesneedtosupporthighqualityscience withoutfavouringhighlyfundedgroupsortopics. Thiscanbebestachievedwithmoderateuserfees, basedonconsumablecost. • Standardizeduserfeesforcomparabletechnologiesacceptabletothecommunityandthefunding partnersshouldbedevelopedatthenationaland Europeanlevel. Itisgenerallyconsideredthatafterapproximatelyfive yearsastate-of-the-artmicroscopeisoutdated.This correspondstotheproductcyclesofcompaniesthatare ontheorderof5-10years,dependingonthetechnology.Discussionsshowedthatthepathtocommercializationofanewideaandthepotentialmarketforthe correspondingproductisilldefinedandunnecessarily long.Whilecompaniesonlydevelopnewproducts,if thereisamarket,itisnotclearwhodefinesthispotentialmarket.Somenewmicroscopictechniqueshave beenlaunchedtooearly,i.e.immatureorwithoutclear scientificapplication,othersonlywithconsiderabledelayholdingbacktheirpotentialinansweringimportant researchquestions. Problemsindefiningapotentialmarketincludehowto provetheutilityandapplicabilityofanewtechnique, ifthereisonlyoneprototype.Totestthevalueofnew ALMinventionsandopenthemtomoreusers,early duplicationofinstrumentsindeveloperlabsand/orprovidingcopiestoothermultiplicatorlabsisconsidered 17 veryuseful,butcurrentlynofundingmechanismsexist tosupportthis. Onceutilityatasmallscalehasbeenestablishedwith severalusersanddependabilityoftheinstrumenthas improved,offeringnewtechnologiestoabroaderuser baseincollaborationwithcorefacilitiesisveryuseful. Thiscanbeakeystepinevaluatingmaturity,robustness andmarketpotential.Commercializationtoprovide turn-keyinstrumentstotheentirecommunityisthen theobviousnextstep.Thiswoulddefineaclearinnovationpipeline,fromdevelopergroup,vialocalduplicationofinstrumentsandrestrictedaccess,tobroader useraccesswithinacorefacility,andfinally,towide distributionviacommercialization.Thispipelinewould evaluateutilityandsizeofuserbaseandthusmarket potentialateverystage,avoidingmanyoftheproblems thatexisttoday. Fromtheviewofthescientists,theintellectualproperty shouldnotbegiventoindustrytooearly,especially forsoftwareapplications,butshouldratherstaywith thescientistsaslongascommercialpotentialandbest industrialpartnerforcommercializationisunclear.On theotherhand,someindustrialpartnersbelievethat thedevelopmentshouldbedonebyR&Dinindustry, notwithintheuniversities. 18 Thecaveatofthisisthatdevelopmentinindustryis furtherawayfromtheresearchneedsandapplications andhasmuchlongerinnovationcycles.Itisworth notingthatmostoftherecentmajorinnovationsin AdvancedLightMicroscopythathavemadealsomajor commercialimpact,suchasconfocal,twophotonand super-resolutionmicroscopyalloriginatedfromacademicdeveloperlaboratories. Againcorefacilitiescanplayakeyroletobridgethe gapbetweendevelopersandindustryandcouldbe complementedbydedicatedpartneringactivitiesto providearegularforumforcontactsbetweenresearch groups,corefacilitiesandcompanies,whichisoneof thegoalsoftheEuro-BioImagingIndustryBoard. Recommendations • Aclearpipelineforcommercializationofnew technologydevelopmentshouldbedefinedthat allowsearlyuseraccess,timelyevaluationofmarket potentialandrapidcommercialization. • Corefacilitiesshouldplayakeyroleinbridgingthe gapbetweenacademiaandindustry. • Thedialoguebetweenacademiaandindustry shouldbefosteredandsupported. Software Softwaretoolsinmicroscopysupportdataacquisition, microscopeoperation,andimportantlycomputational handlingandanalysisofdigitalimagedata.Standardisationandopenaccessforthescientificcommunity arekeyrequirementsforacademicresearchtoensure reproducibilityofresultsanddisseminationofmethods.Theavailabilityofadequatesoftwaretoolsand standards,especiallyforimagedatamanagementand analysisiscurrentlyunsatisfactory. Thereasonsaremanifold: • Thebroadrangeandrapiddevelopmentofimage basedresearchapplicationsmakescommercialisationdifficultandtooslowtosatisfyuserneeds. • Fundingforsustainableacademicsoftwaredevelopmentisdifficulttoobtain,evenmoresoforimplementinguser-friendlyready-to-usesoftware,than fordevelopingnewalgorithms. • Arewardsystemforopenaccessandopensource softwaredevelopmentismissing. • Softwareoftendependsoncompaniesandtheir proprietarydataformatsthatarenotstandardized and/orchangerapidlywithnewsoftwareversions. • Metadataisveryimportantforusingandinterpretingtheimagedatacorrectly.However,metadataof theexperiment,i.e.theinstrumentsettings,areoftendifficulttoaccessindependentlyfromthecompany’sproprietarysoftware.Metadataandprotocols regardingforexamplethesamplecompositionand preparationareofteninsufficientlyrecordedbythe users,ifatall. • Publicdomainsoftwareisdevelopedonmanydifferentsoftwareplatformsandisoftendifficultor impossibletouse,becauseitisnotuser-friendly. Asaresultthecurrentlandscapeconsistsofmany independentlydevelopedsoftwaretoolsthatarenot standardizedorinteroperableintermsofthedatainput andoutput,whichhasmadecommunityeffortsat standardizationinefficient.Evensomeofthemostsuccessfultoolsoftendependontheengagementofone orveryfewenthusiasticindividuals,endangeringtheir sustainability. 19 20 Therearecurrentlyseveraleffortstoimprovethisunsatisfactorysituation.TheOpenMicroscopyEnvironment (OME)andbio-formatsinitiativehavegreatlyimproved standardsofbothrawimageandmetadataandsignificantlyimprovedinteroperabilityofdatabetweendifferentsoftwaretools.Thesedatastandardsarebecoming widelyacceptedbyusersandindustryalsofornew releasesofcommercialsoftware.Theleadingmanufacturersofmicroscopesandaccompanyingsoftwareare nowOMEcommercialpartners.OMEisalsooffering openaccessdatahandlingandmanagementsupport. Recommendations: Inaddition,thereisaconvergencetoonlyafewdevelopmentsoftwareplatformsforimageanalysis.Most widelyusedistheopensourceprojectImageJ,which willbesustainedasImageJ2intheUnitedStatesand hasabroaduserandplug-indevelopercommunity. Inaddition,Matlabhasestablisheditselfasasecond widelyuseddeveloperplatform,whichisalgorithmicallymorepowerful.However,thenumerousMatlab toolscurrentlylackthemodularintegrationthatImageJ plug-insallow.Finally,thereisstillarelativelylarge groupofmorespecializedsoftwareenvironmentsto supportspecificdataanalysistasks,whichagainwould benefitfrommorestandardizationandintegration.A majorchallengeforthefuturewillbetoimplement newpowerfulmultidimensionaldataformatsforimage andmetadatathatreflecttheincreaseindimensionalityofimagedatadrivenbytherevolutioninimaging technologies. • Fundingorganisationsshouldrequestopenaccess todataandsoftwaretoolsthattheysupportintheir fundingprogrammes,therebyprovidinganincentive forrapiduptakebycompanies. • Datastandardizationneedstoproceedfurtherand standardsshouldbeuniversallyusedandaccepted alsobyindustry.Itshouldbepossibletolearnfrom communitiesthathaveestablisheddatastandards andcross-validatedsoftwaretools,e.g.macromolecularx-raycrystallographywiththeirsuccessful CCP4initiative7,orastronomerswiththeirFITS format.Newmultidimensionaldataformatswillbe neededinthefutureatthecoreofimageacquisitionandanalysis. • Whereverpossible,integrationintoexistingand standardizedopenaccesstools,suchasOMEand ImageJorMatlabpackagesshouldbeencouraged fornewsoftwaredevelopments,unlessthereare strongscientificreasonsthatrequirenewplatforms. 7Seehttp://www.ccp4.ac.uk/ Data Challenge Thefieldofopticaltechnologyandlightmicroscopyis veryrapidlyadvancingandexpanding.Forexample, increasinglymultidimensional,high-throughputaswell assuper-resolutionlightmicroscopywillbeimportant andwidelyusedmethodsforfutureresearch.Those methodscangeneratebetweenmultipletensofGBup toseveralTBofdataperexperiment,whichtranslates tomassivelyincreasingdataproductionvolumesper investigator.Therefore,datacompression,storagenetworkbandwidthaswellascrossplatforminteroperabilityhavebecomecriticalissuesforITinfrastructuressupportinglifescienceresearchthatusesALMmethods.At manyinstitutesthebioinformaticsinfrastructureneeds betterequipmentorupgrading.Veryofteninstallation ofnewITinfrastructurerequiresspecificprerequisites suchashosting(personnel)andevenhousing(e.g.air conditioning). “Over the past twenty years there have been great advances in light microscopy with the result that multidimensional imaging has driven a revolution in modern biology. The development of new approaches of data acquisition is reported frequently, and yet the significant data management and analysis challenges presented by these new complex datasets remain largely unsolved. As in the well-developed field of genome bioinformatics, central repositories are and will be key resources, but there is a critical need for informatics tools in individual laboratories to help manage, share, visualize, and analyze image data.” Assystematicandquantitativeimagingstudiesare becomingfeasible,importantnewscientificinsights canbegainedbyre-analysisofreferencedatasets aftertheirinitialpublication.Openaccesstoproperly standardizedandcuratedexistingmicroscopyreference dataisthereforeveryimportantforthecommunity. Comparabletothepublicgenome(andstartingnow alsoproteome)dataresourcesinbioinformatics,itis desirablethatimportantmicroscopydataisreadily availablethroughcentralandpubliclyaccessiblestorage repositories.Thestandardizationrequiredfordepositing dataintosuchrepositories,andforsharingandmaking datacommonlycomputableiscurrentlyunderway. Localcapacitiescanthenbeusedforcomputing,e.g. parameterizing,analyzingandvisualizingthedata. However,localITinfrastructuremustbeconsideredand includedinalargerstrategiccontext.Gradualupgrades continuouslyfollowingthegrowingdemandofdata centresaremorecostlyandlessefficientthenwellplannedrenewalsofITinfrastructurewithintheframeworkofanoverallITconceptforthewholeinstitution, countryandultimatelyEuropeanlandscape.Because ofthelargevolumeofindividualimagedatasetsand thelargesizeofindividualfiles,networkbandwidthbetweenlifescienceinstitutionsisfrequentlyinsufficient foreffectivedatatransferandsharing.Cloudstorage andremotecomputingconceptsforprocessingshould thereforebeevaluatedinthemediumterm. (From:SwedlowJR,GoldbergIG,EliceiriKW(2009)Bioimage informatics for experimental biology.Annu.Rev.Biophys. 38:327-346.) 21 Technology Outlook SimilartogenomicsthecostsforITandcomputational analysisinALMarealsorelativelysmallwhencompared tothoseoftheproductionofpioneerdatasets,suchas thefirsthumangenome,orthefirstmicroscopy-based genomewidescreens.However,asdataproduction technologymaturesandincreasesinthroughput,ITand computationalcostsquicklybecomeasignificantpart ofresearchprojectsusingALMtechnologies.Inaddition,thecriticalstepsofdataprocessingandanalysis becomeincreasinglythebottleneckinproducingscientificresults,andaretoooftennotadequatelycovered bythefundingprogrammes.Especiallysmalleruniversitiesandinstitutesneedtobewellawareofthetotal costsofALMincludingbothimagedataproductionand analysis.EspeciallyupgradingITcanbringunexpected andunplannedforfollow-upcosts,iftheoverallIT structureisnotpreparedforit,e.g.regardingbuilding infrastructureandnetworkbandwidth. Thediscussionwithandamongscientistsallowedassemblinganumberoftopicsthatwereseenasrelevant technicaldevelopmentsinlightmicroscopyinthenext years: • highthrough-putmicroscopyforsystemsbiology • multidimensionalmicroscopy • 3Dand4Dimagingofmodelanimalsandembryos fordevelopmentalbiology • lightsheetbasedmicroscopy • singlemoleculeimaging,especiallyinlivespecimen • multiphoton,including2ndand3rdharmonic,3D imagingoflivespecimen • super-resolutionmicroscopy/nano-microscopy/ isotropichighresolution • non-linearexcitationtechniques Recommendations • ITinfrastructureandbioinformaticsshouldbeseen asintegralpartsofALMcentresorplatformsand needtobeincludedalsoinearlystagesofplanning. • Sufficienthumanandfinancialresourcesneedtobe providedtomeetthedatachallenge. 22 • photo-perturbationmethods • betterfluorophoresandnewlabellingtechniques • reductionofphototoxicityinlivecellimaging • automatedimageprocessinganddataanalysis Conclusions AdvancedLightMicroscopyisanessentialtoolformodernlifesciencesandarapidlyadvancingandexpanding areaofresearchandtechnologydevelopment.Europe currentlyholdsaninternationallyleadingpositionin boththedevelopmentaswellasthebiologicalapplicationsofALMmethods.Howevertomaintainthis leadingpositionandtorealizethefullpotentialofALM methodsforgeneratingknowledgethroughresearch andforbenefitingsocietythroughtechnicaland medicalinnovations,ALMneedsbettersupportand organization.Thekeyconclusionsofthisreportcanbe summarizedasfollows. • Inmostcases,commercialALMtechnologiesbenefit frombeingaccessibletoresearchersincorefacilities withmoderateuserfees. • Corefacilitieswillplayakeyroleintheresearch infrastructurelandscapebyimprovingaccessto ALMtechnology,trainingandsupportingusersand facilitatingtechnologydevelopmentandcommercialization. • Tofulfilthisrolenewfundingandevaluation schemesforcorefacilitiesandtheirexpertstaffare necessary • Thevolumeofimagedataincreasesatunprecedentedspeedsandmakesstandardizationofsoftware anddataformatsaswellasinvestmentinALM relatedITinfrastructure,datarepositoriesandnew analysistoolsahighpriority. 23 About Euro-BioImaging When will Euro-BioImaging be launched and its benefits realized? Euro-BioImagingisalarge-scalepan-Europeanresearch infrastructureprojectontheESFRIRoadmap.Itsmission istoprovideaclearpathofaccesstoacompleterange ofessentialimagingtechnologiesforeverybiologist andbiomedicalscientistinEurope.Euro-BioImagingwill deployadistributedbiologicalandbiomedicalimaging infrastructureinEuropeinacoordinatedandharmonizedmanner.Byprovidingaccesstoandtraininginimagingtechnologies,andbysharingofbestpracticeand imagedata,Euro-BioImagingwillbecomeanengine thatwilldriveEuropeaninnovationinimagingresearch andtechnologies. Who is behind Euro-BioImaging? PreparatoryPhasePartners Euro-BioImaginghasastrongandgrowingsupporter base.Theconsortiumoftheinitialprojectphaseis scientificallycoordinatedbytheEuropeanMolecularBiologyLaboratory(EMBL,DE)andtheEuropean InstituteforBiomedicalImagingResearch(EIBIR,AT).It comprises39beneficiariesfrom15EuropeanMember Statesandassociatedcountries,andmorethan180 associatedpartnersfrom26EuropeanMemberStates andassociatedcountries.Euro-BioImagingisformally endorsedbyover250universities,researchcouncils, fundingbodies,ministries,andindustrypartners. Collaborationwithnationalimagingcommunities Furthermore,theEuro-BioImaginginfrastructureproject isthedrivingforcetoorganizetheEuropeanbiological andbiomedicalimaging.Thefirststepinthisprocessis theself-organizationofnationalimaginginfrastructure providersintheMemberStatestodefinetheirneeds andcapabilities.ThesecondstepistoformapanEuropeancommunityofimaginginfrastructureprovidersfromtheMemberStatesthatsupportstheEuroBioImagingprinciplesofcoordinationandharmonized infrastructuredeployment,openaccessandhighest trainingstandards. 24 Preparatory Phase:2010-2013. Aconstructionplanforapan-Europeanresearch infrastructureforbiologicalandbiomedicalimaging technologiesisdeveloped.Thelegal,governmentaland financialframeworkforimplementationoftheEuroBioImaginginfrastructureisbeingestablished.Costs are€7.9mwith€5.2mfundedbyanEUFramework contract. Construction Phase:2014-2017 TheEuro-BioImaginginfrastructurewillbedeployedby eithernewlyconstructedormajorupgradesofexisting facilitiesfundedmainlybyMemberStates.Totalanticipatedcostsareoftheorderofseveral€100m,butdue tothemodularnatureofEuro-BioImaginginfrastructurenodes,investmentcanbescaledtonationalneeds andcapabilities. Operational Phase:2017onwards Euro-BioImagingwillprovidetrainingprogrammesin andaccesstostate-of-the-artimagingtechnologiesina distributedinfrastructureofimagingfacilitiesthroughoutEurope.Operatingcostswillbeapproximately20% ofconstructioncostperyeartoensurecontinuoustechnologyupgrades andtheprovisionofhighlytrainedstaff.Qualityof servicewillbecontinuouslyreviewed.FundingmechanismsthroughamixofEuropeanandMemberState measureswillbelaidoutinthePreparatoryPhasebusinessplan. Euro-BioImaging webpage and contact www.eurobioimaging.eu Dr.JanEllenberg(ScientificCoordinator,ALM) Dr.AntjeKeppler(ProjectManager,ALM) EuropeanMolecularBiologyLaboratory(EMBL) Meyerhofstr.1, D-69117Heidelberg Tel.+496221387-8847 [email protected] ACCESSTOIMAGINGTECHNOLOGIES: IMAGINGDATA: Euro-BioImagingwillallowscientistsfromallMemberStatestoaccessabroadrangeofcuttingedge imagingtechnologiestheyrequirefortheirvaluable biologicalormedicalresearch.Euro-BioImagingwill guaranteethatinvestmentinimaginginfrastructure isusedinthemostcost-effectiveandefficientway byapplyingEuro-BioImagingqualitystandardsin management,accessandserviceofimagingfacilities. Biologicalandbiomedicalimagingwillbecome oneofthemajordataproducersinthefutureand researchersarefacingunprecedentedchallenges concerningimagedatamanagementandanalysis. TheEuro-BioImaginginfrastructurewillofferplatformsforstoring,sharingandprocessingbiological andmedicalimagingdataonalargescale. TRAINING: Standardizedandhighqualityeducationoftomorrow’sscientistsinapplyingadvancedimagingtechnologiestostudythesinglecelltotheentirehuman beingwillbeoneofthemajorchallengesinbiology andmedicine.Specifictrainingprogrammesat Euro-BioImagingfacilitieswillcomplementnational effortsineducationandMemberStateswillbenefit fromanincreaseinexpertise. ECONOMICVALUE: ImplementingtheEuro-BioImaginginfrastructure withitsnodesindifferentregionsofEuropewill bringnewjobopportunitiesandperspectivesfor researchers,engineers,administrativeandrelated staff.Thesepositiveeffectswillalsoradiateintothe surroundingareasoftechnologydevelopmentand services. EUROPEANRESEARCHAREA: Euro-BioImagingcloselycooperateswithallBiologicalandMedicalSciencesResearchInfrastructures toovercomethefragmentationoftheEuropean researchlandscape. 25 About ERA-Instruments The programme The ERA-Instruments website Ithasbecomeincreasinglyobviousthatconceptsand strategiesforresearchinfrastructure(RI)fundingshould beharmonisedandcoordinatedwithintheEU.ESFRI hasdeterminedrequirementsforEuropeanRIfunding andhaspresentedaroadmap.Growingattentionis paidtolifesciencesthatrelyonRIsofalesscentralised, butmorenetworkeddimension.Thereisaclearneed foractionintheinterdisciplinaryareabetweenphysics, chemistry,biologyandmedicalsciencesascuttingedge instrumentationbecomesincreasinglyexpensiveand, yet,indispensable forworld-classresearch. ERA-InstrumentsisfundedunderFP-7throughthe “capacities”specificprogramme. However,promotionofresearchpolicies,apartfrom theESFRIprojects,hasbeenrestrictedsofartonational effortswithoutmanagingtheseactionswithaEuropeanview.Fundingandresearchorganisationscannot affordtoremainatthenationalstagewithworld-wide competitionforthebestscientistsandthemostpromisingprojects.Frontierresearchisinternationalsincelong andfundingorganisationshavetofollowscientiststo theEuropeanlevel. 26 www.era-instruments.eu Contact to ERA-Instruments JohannesJanssen DeutscheForschungsgemeinschaft(DFG) Kennedyallee40 53175Bonn Tel.+49228885-2430 Fax+49228885-2777 [email protected] ERA-Instruments Partners • • • • • • • • • • • • • • • • Deutsche Forschungsgemeinschaft (DFG), Germany (Coordinator) Centre National de la Recherche Scientifique (CNRS), France Biotechnology & Biological Sciences Research Council (BBSRC), United Kingdom Consiglio Nazionale delle Ricerche (CNR), Italy Ente per le Nuove tecnologie, l‘Energia e l‘Ambiente (ENEA), Italy Netherlands Organisation for Scientific Research (NWO), Netherlands Consejo Superior de Investigaciones Científicas (CSIC), Spain Archimedes Foundation, Estonia The Icelandic Centre for Research (RANNIS), Iceland The National Hellenic Research Foundation (NHRF), Greece Grantova agentura CR (GACR), Czech Republic Fonds Wetenschappelijk Onderzoek (FWO), Belgium Hermann von Helmholtz-Gemeinschaft Deutscher Forschungszentren e.V. (Helmholtz), Germany Wellcome Trust (Wellcome Trust), United Kingdom Ministry for Science and Research (BMWF), Austria Medical Research Council (MRC), United Kingdom 27 ERA-Instruments Euro-BioImaging Coordinator: Deutsche Forschungsgemeinschaft (DFG) Kennedyallee 40 53175 Bonn Coordinator Light Microscopy: European Molecular Biology Laboratory (EMBL) Meyerhofstr. 1 69117 Heidelberg www.era-instruments.eu www.eurobioimaging.eu ERA-Instruments and Euro-BioImaging are supported by the European Commission within the Seventh Framework Programme, Grant Agreement no. 211928 (ERA-Instruments) Grant Agreement no. 262023 (Euro-BioImaging)
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