Annual Report 2014/15 - IUPHAR/BPS Guide to ?· Good health and luck for 2015 ahead. ... database linking…

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  • NCIUPHARAnnualReport

    2014/15

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    BackgroundtoNCIUPHARNCIUPHAR was initiated in 1987 at the Xth International Congress of Pharmacology in Sydney. In 1989, theExecutive Committee of IUPHAR named Paul Vanhoutte (Hong Kong) as chairman of a revised and enlargedcommittee, with Michael Spedding (France) as secretary (1990). This committee energetically expanded itsactivities and the number of subcommittees (to 33), eventually producing the first official compendium on theoccasion of the XIIIth International Congress of Pharmacology in Munich in 1998. Robert Ruffolo (USA) wasChairmanofNCIUPHAR from19982002.MichaelSpeddingbecameChairman in2002andwaselectedagain in2006,andassumedthepostofSecretaryGeneralofIUPHARinJuly2015.

    NCIUPHARand itspartnersaredevelopingaknowledgeenvironment thatwillenablestudentsandscientists inacademia and industry,working in areas related to pharmacology and drug/target research, to exploit the fullpotentialoftheconsiderableamountof informationondrugactionavailable inthepublishedscientific literature.Thisknowledgeenvironmentwillbeavaluabletoolforbasicandclinicalscientistsseekingnewapproachesfordrugdiscovery research,andthediagnosisandtreatmentofdisease,andavaluableteaching resource forstudentsofpharmacologyandtranslationalmedicine.

    NCIUPHARhastheobjectivesof:1. Issuingguidelinesforthenomenclatureandclassificationofallthe(human)biologicaltargets,includingall

    thetargetsofcurrentandfutureprescriptionmedicines2. Facilitating the interfacebetween thediscoveryofnewsequences from theHumanGenomeProjectand

    thedesignationofthederivedentitiesasfunctionalbiologicaltargetsandpotentialdrugtargets3. Designatingpolymorphismsandvariantswhicharefunctionallyimportant4. Developing an authoritative and freely available, global online resource, originally called the IUPHAR

    database, incollaborationwiththeBritishPharmacologicalSociety(BPS),which isnowaccessibleviatheIUPHAR/BPSGuidetoPHARMACOLOGYwebportal(GtoPdb;http://www.guidetopharmacology.org),witharemitto:

    provideaccesstodataonallknownbiologicaltargets enablestudentsandscientistsinacademiaandindustry,workinginareasrelatedtopharmacology

    anddrug/targetresearch,toexploitthefullpotentialoftheconsiderableamountofinformationondrugactionavailableinthepublishedliterature

    provideanentrypointintothepharmacologicalliteratureforbasicandclinicalscientistsfromotherdisciplines

    providean integratededucationalresourcewithaccesstohighqualitytraining intheprinciplesofbasicandclinicalpharmacologyandtechniques

    fosterinnovativedrugdiscovery

    OutgoingChairmansstatement2014/15wasanotheryearofremarkableprogressforNCIUPHARinbuildingourlongtermfoundations,inlinewithourstrategicobjectives.ThankstothealltheattendeesatthetwiceyearlyNCIUPHARmeetings(heldalternativelyinEdinburghandParis), thesemeetingshavebeenscientificallyexciting,administrativelyeffective andkept totime!TheGrantholdersmeetingseverytwomonths(held inEdinburghorbyteleconference)havealsokepttheWellcome Trust grant on track in terms of fulfillment of the aims and objectives for the development ofIUPHAR/BPS Guide to PHARMACOLOGY database (GtoPdb) project in collaboration with the BritishPharmacologicalSociety(BPS).

    NCIUPHARhasgrowndramaticallyinrecentyears,includingincreasedexpertsubcommittees,andbranchingintonewerareasthatarehavingadramaticimpactondrugdiscoveryandpharmacology.Theimmenserecentgrowthof drug target knowledge, including their crystal structures, has been amajor support to drug discovery. ThisincludesuseofboththeNCIUPHARclassificationsandtheGtoPdb.Weareapproachingthepointofdefiningofnearly allpotentiallydruggable sites encodedby thehumangenome.However,drugdiscovery successhasnotgrownatthesamerateasourknowledgeofdrugtargets.Thisispartlyduetotheexponentiallyincreasingnumberofdrugrelatedvariablesaswellasarapidlyincreasingknowledgeofreceptorpolymorphisms,whichmaybecrucialindiseasestates,andalsocontributetocontroversy.Thehighlightingofthesevariablesviagroupsofexpertshas

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    beenshowntobeafirststeptowardscontrollingthem. IntheGtoPdb,such identificationandhighlighting istheresultofexpertdrivenanalysisusingour(~90)subcommittees.

    ThemanagementstructureofNCIUPHARand theGtoPdb team,with input from IUPHARExec,BPS,and inputfromASPET,ASCEPTand the JapanesePharmacologicalSociety,hasbeen functioningextremelywell thus far.However,sinceIhaveassumedthepostofSecretaryGeneralofIUPHAR,itisnowapparentthatthecurrentmodelinvolvingcoordinationbyasingleChairmaybetoodifficultataskintheabsenceof,essentially,afulltimepositiondedicated specifically to that role.Atmy request, a StrategicReviewCommittee (SRC)was established at theOctober2014NCIUPHARmeetingheldinParis,withthetaskofreviewingthecurrentstatusofNCIUPHARanditsactivities, and recommending a path/model for going forward in terms ofmanagement and direction of NCIUPHAR. The SRC is comprised of Doriano Fabbro (Chair), Arthur Christopoulos, Steve Alexander and AdamPawson. An initial report with recommendations has been submitted by the SRC to NCIUPHAR, and furtherdiscussionswilltakeplaceattheAprilmeetinginEdinburgh.

    TheGtoPdbteamconsistsoffivefulltimestaffwithaparttimeadministrator,thankstotheagreementbetweenIUPHAR,theBPS,theWellcomeTrustandtheUniversityofEdinburgh.Thishasboostedourcapacityasevidencedbytheexpandednumberofsubcommitteeswhichtheyarenowthenexusof.Thedatabaseteamisefficient,highlymotivated,andledbyProfessorJamieDaviesasthedatabasePrincipalInvestigatorattheUniversityofEdinburgh.OurcollaborationwiththeBPShasalsoproducedTheConciseGuidetoPHARMACOLOGY,thesuccessortotheBPSGuidetoReceptorsandChannels(GRAC).ThefirsteditionoftheConciseGuidewaspublishedin2013/14,andwearenowpreparingfortheproductionofthe2015/16editiondueintheautumn.Thiswillbeanupdatedsnapshotoftheconcise target familysummaries in thedatabase,publishedasaseriesofPDFsasdesktop referenceguides.Thispublicationhasbeenamajoreffortofthedatabaseteamandthe ConciseGuideEditors.TheGtoPdbteamhavealsomadesignificantimprovementsandenhancementstothewebinterfaceanddatabase,whicharedetailedinthisreport.

    Last July,NCIUPHARwas extremelywell represented atWCP2014 in Cape Townwith 7members presentinginspiredplenarylectures,and14membersspeakingineightsymposia.Thiswasafabulousscientificmeetingwithexcellent organization. We now look forward to WCP2018 in Kyoto (congratulations to the JapanesePharmacologicalSocietyonsecuringthis!)andWCP2022inGlasgow(congratulationstotheBPSonsecuringthis!).

    Goodhealthandluckfor2015ahead.

    MichaelSpedding

    OutgoingChairmanofNCIUPHARSecretaryGeneralofIUPHAR

    CurrentandfuturedirectionsforNCIUPHARNCIUPHAR isperhapsthemostpublicsuccessof IUPHAR,and isengaged inamajortask;todefineallthemaindrugtargetsencodedbythehumangenome,andannotatetheminadatabasefreelyaccessibleworldwideand,importantly,linkthemtotherapeuticsandpharmacologicaltargetvalidation.

    Majoreffortscontinuetodefinethemainvariablesindrug/receptorinteractionsincludingtheparametersthatcanlead to variation in receptor function and pharmacology (i.e. biased signalling, splice variation, receptorpolymorphisms,heterooligomerisation,allostericmodulation,posttranslationalmodification,epigenetictargets,noncodingRNAs,andlinkagetomultiplesignallingcascades).Theseareasareofgreatinterestbecausetheymayconsiderablyexpandtherepertoireofpotentialtargetsfordrugdevelopment,andareunderevaluationbyworkinggroups, which will lead to a number of reports about issueswhichareofcrucial importanceforpharmacology.All theseareashavebeenorwillbeworkedon for relevance forpharmacology,andadditionallymaybeuseful

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    fundingapplicationareastoensurethefuturesustainabilityofNCIUPHARactivities,andtheGtoPdbproject.

    The immense recentgrowthofknowledgeaboutdrug targets,with their crystal structures,hashad adramaticimpact on drug discovery and pharmacology, and importantly, NCIUPHAR classifications have been widelyadopted.Inthepastyear,wehavemadegreatstridestoproactively includenewdrugtargets intheGtoPdb,andrecruitexperts toadviseon them; todatewehave>2700annotatedprotein targets in theGtoPdb,with>7500ligands,includingallapproveddrugs(~1200).

    There is growing research interest, academically, clinically and industrially, in the pharmacology of immunity,inflammationand infection indefiningthe immunological/inflammatorytargets indiseasestates,withtheirmainpharmacology.Withintheresearchcommunity,there isanurgentneedforaprecompetitive,unbiasedresourcethat will integrate highlevel expertise in immunity, inflammation and infection, pharmacology andmedicinalchemistry.Atpresent, immunologicalandpharmacologicalknowledgeareheldbyseparatecommunitiesandthebestresourcesfallshortofwhat isneeded.GtoPdb isthebestmolecularpharmacologydatabase,but iscurrentlylimited in the immunity, inflammationand infectionarea.Wehaveapplied totheWellcomeTrust for funding toextendGtoPdbintothisarena,andtoproduceaGuidetoIMMUNOPHARMACOLOGY.

    Wehavealsoapplied for funding foraCOSTAction inneuropharmacology/neuroimmunology.This ispartlyasaresultofourcollaborationwiththeEuropeanCollegeofNeuropsychopharmacology (ECNP)andmembersoftheNomenclatureTaskForce fordrugs inpsychiatry.There isa longway togobut,asa firststrategic step,wearecollatingthedrugsindevelopmentforAlzheimersandseveralexamples(inconjunctionwithECNP)inpsychiatry,datatrawling,andlinkingwithexpertsubcommittees.Thus,wewouldnotonlybeabletoregrouptargetsbytype,butalsobytherapeuticindication.Thiswouldbeofgreatusetopatientgroups.

    Anexcitingchallengeon thenot toodistanthorizon isour 'OneHealth' Initiative;OneBiology,OneHealth,OneMedicine:An IntegratedDatabaseforthePharmacologicalActionofDrugs inHumans,DomesticAnimalsandModelOrganisms.WewillbesubmittinganapplicationtotheBBSRCforfundingtodrivethisinitiativeinduecourse.Weare moving towards encouraging our subcommittees of experts to include information on translationalpharmacology on drug targets.Wewill also be extendingGtoPdb into the area of stem cell pharmacology (adatabase linkingstemcellsciencewithexpertlycuratedpharmacologicalknowledge),andalso into thecriticallyimportantarenaofenvironmentalpharmacology(adatabasethatprovidescomprehensiveinformationondefinedandemergingpesticiderisks,includingtheiraffinitiesandpotencyinidentifiedspecies).However,giventhecurrentbudgetaryclimate(seeAppendixV:Fundsavailableasof31stMarch2015**),thisisallreliantonfunding,whichwearevigorouslypursuing.

    Finally,workingwith theUniversityofEdinburghDrupalWebsiteService,andwith funding fromASPET,SimonMaxwellhasspearheadedthedevelopmentoftheIUPHAR/ASPETPharmacologyEducationProject,aneducationportalthatwillbecloselylinkedwiththeGtoPdb.Itwillprovideaccesstohighqualitytrainingintheprinciplesandtechniquesofbasicandclinicalpharmacology.

    OrganisationofNCIUPHARCorecommittee

    ThecorecommitteeofNCIUPHARislistedinAppendixI.ThebiannualcoreNCIUPHARmeetingsarethemedandwehaveestablishedanalliancewiththeJapanesePharmacologySocietywhopaythetravelfortwomembers*,butwhoareinvitedaccordingtothemeetingthemes.

    CorrespondingMembers

    Inordertobroadentheexpertiseofthecorecommittee,thenumberofcorrespondingmembers(seeAppendix I)hasbeen further increased, to include7newmembers:DavidGloriam (UniversityofCopenhagenandGPCRDB,Denmark),GillianGray(UniversityofEdinburgh,UK),BongKiunKaang(SeoulNationalUniversity,Korea),StefanKnapp (Structural Genomics Consortium, UK),Margaret (Mandy)MacLean (University of Glasgow, UK), FionaMarshall (Heptares, UK) and Georg Terstappen (AbbVie, Germany). Corresponding members attend selectedmeetingsofNCIUPHAR and are invited according to themeeting themes.They include representativesof themajorpharmaceuticalcompanies.

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    EvolvingPharmacologyGroup

    AnthonyDavenport leadsagroupwhichmonitorsthe deorphanisationofGPCRsandevolvingpharmacologyofdrugtargets ingeneral.Particularly importantandtimelybreakthroughsare included intheHotTopicssectionofthedatabasealongwithemailalerts.

    ClinicalTranslationalPharmacologyGroup

    Inordertoprovideadviceonthetranslationalaspectsofdrugtargetpharmacology,asubgroup(seeAppendixI)ofclinicalpharmacologists(coremember,SirColinDollery)discusshowbesttorespondtothewishesofourclinicalcolleaguesandtotranslateactivityatdrugtargetsitestoclinicalefficacy.

    Subcommittees

    Chairpersons(seeAppendixII)proposealistofexperts,ratifiedbyNCIUPHAR,toensureadequaterepresentationof the field. The chairperson of each subcommittee plays a critical role coordinating the actions of thesubcommittee, organising meetings, finalising documents and the website pages. However, we encouragepostdocstojointhesubcommittee,aschairssimplydonothaveenoughtimetofillinthevarioustemplatefieldspostdocscanthereforegetpublicationcredits,andseveralNCIUPHARpublicationshavebecomecitationclassics.ThehindexofNCIUPHARis>74.Thesubcommitteesmeettoestablishconsensusonclassification,andtoensurethattheNCIUPHARguidelinesare compliedwith.Wenowhavemore>90subcommittees(seeAppendixII).

    PublicationsandOutreachRecentpublications

    NCIUPHAR has built its reputation on the basis of its published articleswith nomenclature recommendationswhichareadoptedworldwide.NCIUPHARhasanhIndexof74 forarticleswhichcarry thebadge IUPHAR.NCIUPHAR has a longstanding, formal collaboration with ASPET and Pharmacological Reviews, and the officialnomenclature reports are published in the journal. In addition, our collaborationwith the BPS has led to thepublication of a series of general stateofthefield review articles (alongside database updates) in the BritishJournalofPharmacology.

    EightNCIUPHARnomenclaturereports(seeAppendixIII)haveappearedinPharmacologicalReviews(Editor,EliotOhlstein) so far during the 2014/15 period, reflecting the activity of NCIUPHAR. In addition, 12 NCIUPHARcommissioned reviews for theBritish JournalofPharmacology (EditorinChief, IanMcGrath)have recentlybeenaccepted(seeAppendixIII).

    Duringthesecondhalfof2014,AdamPawsonandthePressEditorsattheBritishJournalofPharmacologystartedimplementing links directly from all published review articles (starting initially with the IUPHAR reviews) andresearch articles toGtoPdb entries.All articles (since ~August 2014) now include a Table of links beneath theabstractlistingalltargetsandligandsinthearticlewithhyperlinkstothecorrespondingentriesintheGtoPdb,thusallowingreadersinstantaccesstothewealthofinformationcontainedinthedatabase.

    Newsletter

    ThebiannualNCIUPHARnewslettercontinuestobedistributed inthespringandautumn,throughamailing list(usingMailChimp EmailMarketingandEmailListManagersoftware)comprisingall IUPHARmembersocieties,NCIUPHAR subcommittees and collaborators, pharmacology departmentsworldwide, and database userswhohave signedup to receive news alerts; and wasmade available for download from GtoPdb homepages. ThenewsletterwasalsoadvertisedonsocialmediaandtheRSSfeed.

    GtoPdbteamrepresentationofNCIUPHARatconferencesandmeetings

    TheactivitiesofNCIUPHARhavebeenpromotedbyNCIUPHARrepresentativesatthefollowingconferencesandmeetingsduringthepastyear:

    The7th InternationalBiocurationConference (InternationalSociety forBiocuration),Toronto,April2014;HelenBenson

    ComputationalChallengesinDataCitationworkshop,Philadelphia,April2014;JoannaSharman;

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    The GLISTEN Barcelona GPCR Spring Conference 2014, GPC...

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