Call 2016: `Small animal models and rare diseases`

Call2016:‘Smallanimalmodelsandrarediseases’
TheFrenchFoundationforrarediseases(Fondationmaladiesrares)ispleasedtolaunch,
incollaborationwiththeFrenchNationalInfrastructureTEFOR,itssecondcallfor
proposals:developmentandstudyofsmallanimalmodels-excludingmousemodels-
forrarediseases.
A–Contextandaimsofthecall
A1.Presentation
TheFrenchFoundationforrarediseases(Fondationmaladiesrares)promotesandsupports
researchonrarediseases.ThisFoundationwascreatedin2012,asakeyfeatureactionofthesecond
French National Rare Disease Plan (2011-2014). It is operating with public and private sources of
funding to stimulate, coordinate and support fundamental, clinical and translational research.
Founders include the French Muscular Dystrophy Association (Association Française contre les
Myopathies – AFM-Téléthon), Alliance Maladies Rares, the French National Institute of Health and
Medical Research (Inserm), the Conference of General Directors of the French University Hospitals
and the Conference of Presidents of French Universities. The Foundation plays a pivotal role,
coveringalldomainsofresearchinrarediseases,withastrongemphasisontranslationalresearch.
TheFoundationpromotesandsupportsresearchonrarediseasesthroughspecificcallsforprojects.
Inthiscontext,oneofthemainobjectivesoftheFoundationistofacilitateaccessforresearchersto
strategic technology platforms by providing financial support. All the scientific activities of the
Foundation are directed by its Administrative Board, composed of presidents or representatives of
the5foundingorganizationsand8qualifiedindividuals.TheFoundationbenefitsfromtheguidance
of a Scientific Advisory Board composed of internationally renowned physicians and scientists, key
opinionleadersinthefieldofrarediseases.
TEFORisaFrenchinfrastructurethatpromotesinnovativeservicesandtoolsforresearchon
Drosophila, Zebrafish and other model organisms. TEFOR provides cutting-edge integrated services
for transgenesis, genome editing and phenotyping. A growing number of academic platforms now
facilitate access of research teams to innovative and rapidly evolving technologies applied to the
generationofgeneticallyengineeredanimalsfromalargepanelofspecies.
TEFORbringsthreeplatformstogether:AMAGEN,dedicatedtosmallfish,speciallyZebrafish,theFLY
FACILITYforthefly,andTRIP,theRattransgenesisplatform.Othernationalplatformsgivesupport
for the generation and characterization of models in the xenopus (CRB, the Xenopus transgenesis
platform)andtherabbit(theRabbittransgenesisplatform).
Callforprojects‘Smallanimalmodelsandrarediseases’-Fondationmaladiesrares/TEFOR–April2016–page1
A2.Context
Animal models are essential tools to get insights into physiological processes and improve the
understandingofmolecularandcellularmechanismsleadingtopathologicalconditionsrelatedtoa
raredisease.Theyhaveproventobeusefulforthedevelopmentofnewdiagnosticandtherapeutic
approaches.
Mouse models are common for the study of human diseases and have already demonstrated the
extentoftheirimpact.TheFrenchFoundationforrarediseasesalreadysupportsresearchteamsfor
thedevelopmentandcharacterizationofmousemodels(Callmousemodelsandrarediseases).
However,someothersmallanimalmodelscouldalternativelybeusedaccordingtothe3Rrule.They
maypresentsomeclosephysiologicalsimilaritiesandbettermimicadisease.
They may furthermore provide a number of exceptional advantages, such as to obtain quicker
results,bettermonitoringandmodelingofphysiopathologicalprocessesthatcanonlybefollowedin
vivoandtoperformintegratedstudies(-omics)andscreeningofphenotypicchangesinresponseto
geneticalterations(suchaspangenomicscreen)orsmallmolecules.
Choosinganappropriateandreliableanimalmodelisofparticularimportance.Insomecasesalso,it
canbeadvantageoustouseseveralcomplementaryanimalmodelstocoverdifferentaspectsofthe
samedisease(transversal/integrativeapproaches).Inaddition,theuseofoneormoresmallanimal
modelscanrepresentakeystepbeforetheuseoflargeanimalmodelsintheearlystageofclinical
applications,inordertovalidateinvivoaproofofconcept.
Genome editing represents a technological revolution that allows the generation of animals
modelinghumandiseasesineveryorganism.Advancesinthemethodologiesthatcanbeappliedto
small animal models extend opportunities in rare diseases research and new avenues towards
addressingtherapeuticapproaches.
A3.Objectives
This call aims to give a significant boost to the generation and characterization of small animal
models of rare diseases, in order to get a better understanding of pathophysiological mechanisms
involved in rare diseases and to provide evidence for therapeutic proofs of principle that may
eventuallybetranslatedintorarediseasespatientscare.
Another objective of this call is to favor new collaborations between rare diseases research teams
and groups with extensive experience with a particular animal model, helping the development of
interestingandinnovativemodelsandtherelatedfunctionalstudies,whichwouldleadtosignificant
advancesinrarediseasesresearch.
Callforprojects‘Smallanimalmodelsandrarediseases’-Fondationmaladiesrares/TEFOR–April2016–page2
B–Contentofthecall
Successful applicants will have a facilitated access to tools developed by experienced academic
platforms,inordertodevelopsmallanimalmodelsofrarediseases.
The precise type of model development (knock-out, knock-in, humanized model, transgenic…), will
be specific to each organism, but will rely on the latest improvements and most appropriate
techniques of genome editing (ZFNs, TALEN, CRISPR/CAS9, etc.) or more classical transgenic
approaches (such as DNA microinjection, lentiviral infection). The project must be based on
scientifically validated preliminary data and the choice of organism and model must be clearly
justified.
Pilotfunctionalstudiesmaybeconsiderediftherelevantservicesareprovidedbytheplatform,for
example:phenotypingbyadvancedimaging(zebrafish),etc.
Inthescopeofthiscall,animalmodelswillbedevelopedwiththesupportofthefollowingnational
platforms:
Non-mammalianmodels:
-Zebrafish,withtheplatformAMAGEN,Gif-sur-Yvette(TEFORinfrastructure);
-Fly,withtheplatformFLYFACILITY,Clermont-Ferrand(TEFORinfrastructure);
-Xenopus,withtheplatformCRB,Rennes;
Mammalianmodels:
-Rat,withtheplatformTRIP,Nantes(TEFORinfrastructure);
-Rabbit,withthetransgenesisplatformofINRA,Jouy-en-Josas.
Technologies and applications used by each platform for every organism, links to websites and
contactsforeachplatformarelistedinAnnex1.
Principal investigators must contact platforms for a detailed description of services that could fit
the objectives of their project and to obtain assistance in optimizing the technical design. The
technicalvalidationoftheprojectbytheplatformismandatory.Adetailedtimetableandbudget
associatedwitheachstepoftheprojectmustbeprovidedaccordingly.
Theprogressofeachprojectwillbemonitoredandupdatedevery3monthsbytheprojectmanager
oftheplatformandcommunicatedtotheprincipalinvestigator.
Principal investigators may also seek advice from platforms in order to establish appropriate
collaborationswithteamsspecializedintheuseofparticularmodelspecies.
Callforprojects‘Smallanimalmodelsandrarediseases’-Fondationmaladiesrares/TEFOR–April2016–page3
C–Evaluation
C1.Eligibility
TheprincipalinvestigatoroftheprojectmustbelongtoaFrenchresearchteam,affiliatedto
academia (research team working in universities, other higher education institutions or research
institutes) and/or to clinical/public health sector (research team working in state or university
hospitals/publichealthorganizations).
C2.Evaluationcriteria
Thefollowingelementswillbeparticularlyconsideredintheevaluationoftheproject:
• Originalityoftheproject;
• Relevanceofpreliminarydatajustifyingthedevelopmentofthemodel;
• Adequacyofthespeciesandmodelforthehumandisease;
• Clarityofobjectivesandoutcomesoftheproject;
• Prospectsintermsofdiseaseknowledgeandexpectedtherapeuticbenefits;
• Detaileddescriptionandtimetableoftheresearchprogramproposed;
• Qualityoftheteam;
• Integrationoftheprojectintheresearchprogramoftheapplicant;
• Team experience and complementary and synergy of associated partners in model
exploration;
• Positioningoftheprojectinthenationalandinternationalcontext.
C3.Selection
Selectionwillbemadeonapeerreviewmode.Proposalswillbeevaluatedbytwoexternal,
nationalandinternational,academicrefereeswitharecognizedexpertiseonthemodel.Projectswill
then be selected by a scientific ad hoc committee, composed of small animal models experts and
membersoftheScientificAdvisoryBoardoftheFrenchFoundationforrarediseases.
D–Funding
TheFrenchFoundationforrarediseaseswillprovidefinancialsupportforthegenerationof
the animal model and/or if justified and approved, for the characterization of the model by
phenotypingorfunctionalstudies.
Funding will cover costs of services provided by the platform and is not intended to cover
equipment,runningcostsorpersonnelcostsintheresearcher’slaboratory.
Callforprojects‘Smallanimalmodelsandrarediseases’-Fondationmaladiesrares/TEFOR–April2016–page4
E–Proposalsubmissionandscheduleofthecall
Tocompleteandsubmitanapplicationform,pleaseaccesstotheportal“Applicantportal”.
Submissiondeadlineforproposals:July5,2016(5:00pm).
Theprovisionalscheduleofthecallisthefollowing:
April,2016
Launchofthecall
July5,2016
Submissiondeadlineforproposals
September-October2016
Evaluationbytwoexternalreferees
November2016
Selectionbythecommittee
December2016
Publicationoftheselectedprojects
The title of the selected projects and name of their principal investigator will be published on the
websiteoftheFrenchFoundationforrarediseasesbyDecember2016.Thesummarywrittenfora
generalaudiencemaybeusedforcommunicationpurposesbytheFoundationandTEFOR.
ResultsandIntellectualPropertydataresultingfromprojectsfundedthroughthecallwillbeowned
bytheresearcher’sorganizations.
AcknowledgementPolicy:ItisrequiredthatprojectsfundedacknowledgetheFrenchFoundationfor
rare diseases and the TEFOR infrastructure in all publications and communications. Reference(s) of
thepublication(s)mustbesenttotheFoundation.
IRDiRC policies and guidelines: the project partners are expected to follow IRDiRC policies and
guidelines.Formoreinformationseehttp://www.irdirc.org
Callforprojects‘Smallanimalmodelsandrarediseases’-Fondationmaladiesrares/TEFOR–April2016–page5
ANNEX1:PARTNERPLATFORMSOFTHECALL
FlyFacility
organism(s)
Drosophilamelanogaster
localization
GReD,INSERMU1103,CNRSUMR6293,Universitéd’Auvergne,Clermont-Ferrand
website
www.fly-facility.com
contacts
[email protected]
ChristopheJagla:[email protected]
TeresaJagla:[email protected]
phone
0473178181
applications
U6-sgRNAtransgenicstrainsdevelopment
gRNAefficiencytestsinembryos
KOandKImodels
technologies
CRISPR/Cas9
Transgenesis
AMAGEN
organism(s)
Daniorerio
Oryziaslatipes
localization
UMSCNRS/INRAGif-sur-YvetteandJouy-en-Josas
website
http://www.inaf.cnrs-gif.fr/inaf/amagen.html
contacts
FrédéricSohm
[email protected]
phone
0169823412
applications
KOandKImodels
Transgenicstrains,includingGal4strains
Phenotypingbyadvancedimaging(Teforcorefacility)
technologies
CRISPR/Cas9microinjection
TALENmicroinjection
DNAmicroinjection
Imagingtechnics(viaTEFORCoreFacility)
CRBXénopes
organism(s)
Xenopuslaevis
Xenopustropicalis
localization
UMS3387CNRS/UniversitédeRennes1-263,avenueduGénéralLeclercF-35042
RennesCedex
website
http://xenopus.univ-rennes1.fr
contacts
[email protected]
DanielBoujard:[email protected]
ChristopheHeligon:[email protected]
phone
0223235250
0223235251
applications
KOstrains
transgenicstrains
technologies
CRISPR/Cas9microinjection
TALENmicroinjection
DNAmicroinjection
Genotyping
TRIP-Nantes
organism(s)
Rattusnorvegicus
localization
INSERMUMR1064,30,boulevardJeanMonnet,44093Nantes
website
http://www.tgr.nantes.inserm.fr/
contacts
IgnacioAnegon:[email protected]
SéverineMénoret:[email protected]
phone
0240087415
applications
Generationoftransgenicbysmallorlarge(BAC)DNAmicroinjection
GenerationofKIorKOrats
Immunophenotype
technologies
DNA,ZFNs,TALENs,CRISPR/Cas9,PiggyBactransposonandlentiviralvectors
microinjection
Embryofreezing
Q-PCRgenotyping(zygosityanimals)
Identificationoftransgenesintegrationsite(LM-PCR)
Analysisofimmuneresponses
Atelierdemodificationgénétiquechezlesmammifèresnonrongeurs
organism(s)
Oryctolaguscuniculus(NewZealandrabbits,NZ1077)
localization
INRAUMR1198BiologieduDéveloppementetReproduction78350JouyenJosas
website
http://www6.jouy.inra.fr/bdr/Services-communs/Ateliers
contacts
GenevièveJolivet
[email protected]
phone
0134652544
applications
Productionoftransgenicrabbits(additivetransgenesis)
KO,KI,siRNAmediatedknockdown
Designoftransgene,TALEN,gRNA
Phenotypinginvestigation
technologies
DNA,RNAinjection,BACDNAinjection
TALEN,ZFN,CRISPRtechnologies
Genotyping(PCR,cloningoftransgeneintegrationsites)
Ultrasoundanalysis,iDEXA-DualX-rayAbsorptiometry