Murdoch Children’s Research Institute PhD Projects available for 2021

TableofContents

Lab-basedprojects........................................................................................................................4CellBiology.............................................................................................................................................4

1.Developinghighcontentscreensofnoveltreatmentsforcongenitalnephroticsyndrome...........42.Controllingnephronpatterningandsegmentationinkidneyorganoids.......................................43.Regulatingthevascularisationofthehumanglomerulusinvitro.................................................54.Nephrotoxicityscreeningusingstemcell-derivedproximaltubules..............................................55.Developingcomputationalapproachestoanalysedevelopmentanddisease..............................5

ClinicalSciences......................................................................................................................................66.Towardstreatmentofintellectualdisabilitycausedbyerrorsinthechromatinmachinery..........67.Neuropsychologicalprofileofchildrenwithchildhoodapraxiaofspeech.....................................68.Paininchildrenwithcerebralpalsyandotherdevelopmentaldisabilities....................................79.PlacentalCordBloodCellTherapyinChildrenatHighRiskofHeartFailure.................................7

Genetics..................................................................................................................................................810.InvestigatingthemolecularbasisofParkinson’sdiseaseusingnovelgeneticmodels................811.Identifyingthegeneticcausesofbrainmalformationinchildren................................................812.UnderstandingthemolecularbasisofCANVAS-anovelneurologicaldisordercausedbyanexpandedDNArepeat........................................................................................................................913.Developmentofnovelhumanstemcellderivedmodelsofbeta-propellerprotein-associatedneurodegenerationfordiseasemodellinganddrugscreening..........................................................914.Discoveryofnewtreatmentsforbraindevelopmentdisorderslinkedtoepigeneticregulatorygenes................................................................................................................................................10

InfectionandImmunity........................................................................................................................1115.UnderstandingthecauseofHumanpapillomavirus(HPV)-negativecervicalcancersinAustralianwomen............................................................................................................................1116.Immunemechanismsofpeanutallergyremission.....................................................................1117.ThecardiometaboliclegacyofSARS-CoV-2inlongitudinaladolescents....................................1218.Definingthemechanismsthatunderpinthebeneficialoff-targeteffectsofBCG......................1319.UnravellingtheInflammatorySignaturesofPaediatricRespiratoryDisease............................13

PopulationHealth................................................................................................................................1420.PredictorsofinfectionandclinicalseveritywithSARS-CoV-2inextantlongitudinalLifeCoursepopulationcohortsofchildrenandtheirhousehold/familycontacts..............................................1421.Takingplacentatoscale:Thepopulationburdenofdisorderedplacentationandplacentalfunction............................................................................................................................................14

NonLab-basedprojects..............................................................................................................15CellBiology...........................................................................................................................................15

22.Metabolicreprogrammingofthefailingheart..........................................................................15ClinicalSciences....................................................................................................................................15

23.Long-termimpactofmoderateandlatepretermbirth:effectsonneurodevelopment,braindevelopmentandrespiratoryhealthatschoolage.........................................................................1524.Neuropsychologicalprofileofchildrenwithspeechdisorder.....................................................1625.Measuringchildandfamilycentredoutcomesfollowingspinalsurgeryforchildrenwithneuromuscularscoliosis...................................................................................................................1726.Comprehensiveclinicalphenotypingofindividualswithstuttering...........................................1727.Mentalhealthandparticipationoutcomesforchildrenandyouthwithcerebralpalsy............1828.Supportingyoungpeoplewithcomplexdisabilitytoparticipateinimportantlifesituations....1829.Understandinganddefiningsupportivehealth/NDISserviceenvironments.............................1930.Adaptanevidence-basedhealthylifestyleprogramtoanAustraliancontext..........................1931.Optimisinguseofeverydaytechnologyforchildrenandadolescentswithacquiredbraininjury.........................................................................................................................................................20

32.Assessmentandmanagementoffatiguefollowingpaediatricacquiredbraininjury................20Genetics................................................................................................................................................21

33.RareDiseasesNow-Greatcareforrare....................................................................................2134.Implementationconsiderationsforanationalprogramforexpandedreproductivecarrierscreening..........................................................................................................................................22

InfectionandImmunity........................................................................................................................2335.Doseoptimisationofantibioticsinchildrenwithcysticfibrosisusingpharmacokinetic-pharmacodynamicmodelling..........................................................................................................2336.Applicationofintra-oral3-DimensionalScanningtomonitororalhealthinchildren................2337.ClusterRCTofamulti-componentinterventionpackagetoimprovematernalandchildhoodvaccinationinVictoria......................................................................................................................23

PopulationHealth................................................................................................................................2438.Geneticsofchildhoodhearingloss.............................................................................................2439.AssociationsbetweenCOVID-19psychosocialstressorsandimmuneandcardiometabolicmarkersamongadolescents............................................................................................................2540.LongitudinalandseculartrendsinoutcomesforadolescentswithhearingimpairmentinVictoria.............................................................................................................................................2541.Inequitiesinchildren'smentalhealth:evidencetoinformprecisionpolicyresponses..............2642.Theimpactofpositiveandadverseexperiencesonchildren'scardiovasculardiseaseriskandmentalhealthoutcomes..................................................................................................................2743.Improvinglifetimeoutcomesforbabiesinspecialcarenurseries..............................................2744.Precisionpredictionofmaternalandchildoutcomesfromroutinefetalultrasounds...............28

Lab-basedprojects

CellBiology1.DevelopinghighcontentscreensofnoveltreatmentsforcongenitalnephroticsyndromeProfMelissaLittlemelissa.little@mcri.edu.au0399366206Congenitalnephroticsyndromepresentsearlyinlifeandresultsinkidneyfailureandresultingsevereproteinuriawhichcanbelifethreatening.Notreatmentsareavailableforthisconditionotherthanrenaltransplantationanddialysis.Thegeneticallyinheritedformsofthisconditionmostcommonlyresultfrommutationingenesexpressedinthepodocytesoftheglomerulus.Wehavedevelopedamethodforgeneratinghumankidneytissuefrompluripotentstemcellsthatrepresentgoodmodelsofthehumankidney.Wehavealsoestablishedpatientstemcelllinesandgeneeditedstemcelllineswithspecificpointmutationsingenesknowntoresultincongenitalnephroticsyndrome.Thisprojectwouldcharacterisethesemutantkidneytissuesanddevelopahighcontentscreentoidentifycompoundsthatmaybeabletotreatthisdisease.Inthisway,theobjectivewouldbetodeveloppersonalisedtreatmentsforcongenitalnephroticsyndrome.2.ControllingnephronpatterningandsegmentationinkidneyorganoidsProfMelissaLittlemelissa.little@mcri.edu.au0399366206Thehumankidneycontainsapproximately1millionnephronsthatareresponsibleforfiltrationoftheblood,activesecretionofwasteproductsandthereabsorptionofwaterandcriticalmoleculesbackintothebody.Todothis,thefinalnephronneedaround25distinctcelltypeseachwithspecificfunctions.Wehavedevelopedamethodforrecreatinghumandevelopingkidneytissuefrompluripotentstemcells.Thesetissues,referredtoaskidneyorganoids,containpatterningandsegmentingnephronsbeginningtoformeachofthemanyrequiredcelltypes.However,theseremainimmatureandsomecelltypesarenotpresent.Itisalsoclearthatdifferentcultureconditionsfavouroneendofthenephronoveranother.Theaimofthisprojectwouldbetodissectwhatpathwaysaredrivingthepatterningofdifferentnephronsegmentsandcelltypestoimprovethemodeland/orgeneratecelltypesthatarecurrentlymissingorimmature.

3.Regulatingthevascularisationofthehumanglomerulusinvitro.ProfMelissaLittlemelissa.little@mcri.edu.au0399366206Thehumankidneycontainsapproximately1millionnephronseachofwhichiscomprisedofaglomerulusintowhichacapillarybedgrowsandthroughwhichthebloodissubsequentlyfilteredtoformtheurine.Wehavedevelopmentamodelofthedevelopinghumankidneygeneratedfromhumanpluripotentstemcellsthatcontainsformingnephronswithmaturingglomeruliaswellasendothelialcells.However,theefficientwithwhichcapillaryloopsformwithintheseglomeruliislow.Thisprojectwillinvestigatemolecularapproachestoinducegrowthfactorsecretionfromtheglomerulustoimprovecapillaryformationinvitro.Thiswillallowthemodellingofglomerularkidneydiseaseandpotentiallyimprovetissuesurvivalposttransplantation.4.Nephrotoxicityscreeningusingstemcell-derivedproximaltubulesProfMelissaLittlemelissa.little@mcri.edu.au0399366206Thehumankidneycontainsapproximately1millionnephronseachofwhichiscomprisedofaglomerulusintowhichacapillarybedgrowsandthroughwhichthebloodissubsequentlyfilteredtoformtheurine.Wehavedevelopmentamodelofthedevelopinghumankidneygeneratedfromhumanpluripotentstemcellsthatcontainsformingnephronswithmaturingglomeruliaswellasendothelialcells.However,theefficientwithwhichcapillaryloopsformwithintheseglomeruliislow.Thisprojectwillinvestigatemolecularapproachestoinducegrowthfactorsecretionfromtheglomerulustoimprovecapillaryformationinvitro.Thiswillallowthemodellingofglomerularkidneydiseaseandpotentiallyimprovetissuesurvivalposttransplantation.5.DevelopingcomputationalapproachestoanalysedevelopmentanddiseaseProfMelissaLittlemelissa.little@mcri.edu.au0399366206Theuseofcomplex3Dtissuesderivedfromstemcellsaffordsmanysignificantadvantagesforthestudyofdevelopmentanddisease.Theanalysisoftheresultingtissueis,however,complexgiventheirsizeandcellularcomplexity.Advancesinimagingtechnology,transcriptionalprofilingresolutionandmachinelearningprovidethetoolsthatshouldallowhighthroughoutcharacterisationofsuchcomplexstructures.Thisprojectaimstodevelopnovelcomputationalapproachtohandlehighcontentimagedatasetsfortheinterrogationofdiseasemechanism.Theapplicantshouldhavesomebasicunderstandingofcomputationalbiologyand/orimaging.

ClinicalSciences6.TowardstreatmentofintellectualdisabilitycausedbyerrorsinthechromatinmachineryProfDavidAmordavid.amor@mcri.edu.auIntellectualdisabilityoccursin2-3%ofnewborns,foravarietyofreasons,includingenvironmentalfactors,chromosomalabnormalitiesandmutationsinsinglegenes.Intellectualdisabilityresultsinlifetimedependencyonfamilyandsocietalsupport,yettraditionally,ithasbeenviewedasanuntreatablecondition.However,recentlyithasbeenrecognisedthatintellectualdisabilityresultingfrominbornerrorsinthechromatinmachinerymaybetreatable.Morethan40geneticsyndromeshavesofarbeenidentifiedinthiscategory,includingKabukisyndrome,KAT6AsyndromeandKleefstrasyndrome.Thisprojectwillfocusonmutationsinchromatinfactorsandchromatin-modifyingenzymesfoundinpatientswithintellectualdisability,becausechromatinchangesarereversible,andbecausetheseclassesofmoleculesarewellestablishedastherapeutictargetsinotherdisorders.Theprojectwillidentifyandcharacterizemutationsinthechromatinmachineryininfantsandchildrenwithbraindevelopmentdisorders,delineatehumanphenotypesassociatedwiththesemutations,andcharacterizethephenotypic,cellbiological,molecularandbiochemicalconsequencesofthepatient-specificmutationsinmodelsystems.Thelongertermobjectiveistotestpotentialtherapeuticinterventionsingeneticmodelsinvitroandinvivo.Weanticipatethattheinvestigationoftheroleofindividualchromatinmodifierswillgowellbeyondaspecificsyndromeandwillprovideanunderstandingoftheregulationofgeneexpressioninbraindevelopmentandplasticity,potentiallyhighlightingtherapeuticsforpatientswithoutmutationsinthesefactors.Wehopetorecruitahighqualitystudentwishingtoundertakeresearchintogeneticsandneurodevelopmentaldisorders.7.NeuropsychologicalprofileofchildrenwithchildhoodapraxiaofspeechProfAngelaMorganangela.morgan@mcri.edu.au0383416458Childhoodspeechdisordersarecommon,affecting1in20preschoolchildreninthegeneralpopulation.Yetthesechildrenpresentwithmildarticulationorphonologicaldisordersthattypicallyresolvewithorwithoutintervention.Bycontrast,approximately1in1,000patientspresentwithapersistentandlesstractablespeechdisorderknownaschildhoodapraxiaofspeech(CAS).ThreecoresymptomssupportaCASdiagnosis:includinginconsistenterrorsonconsonantsandvowels;lengthenedanddisruptedcoarticulatorytransitionsbetweensoundsandsyllables;andinappropriateprosody(ASHA2007).Lifelongimpairmentisseen,withpsychosocialimpact,literacydeficits,andrestrictededucationalandemploymentoutcomes.WhyisCASsomuchmorepersistentthanotherspeechconditions?Increasingevidencehasshownageneticbasisforupto1in3childrenwithCAS.Novelmolecularpathwayshavealsobeenrevealed,indicatingarolefortranscriptionaldysregulation.ThismechanismisassociatedwithalteredbraindevelopmentwhichresultsintheCAS

symptomatology,alongwithothercommonlyshareddeficitssuchasimpairedmotorskilldevelopment.Todate,fewstudieshaveexaminedneuropsychologicalstrengthsandchallengesinchildrenwithCAS.Agreaterunderstandingofcognitivecontributionstothecondition,combinedwithnewgenomicdata,willleadtomoretargetedtherapeuticinterventionsandhelptoexplainthemechanismswhichleadtothissymptomprofile.OurteamhasanexcitingPhDopportunityforaprojectexaminingcognitivecontributionsinCASassociatedwithourspeechgeneticsclinicattheRoyalChildren'sHospital.3yearstipendoffered.Essentialcriteria:DegreeinClinicalPsychologyorNeuropsychology;HighacademicmarksthatwouldmeeteligibilityforenrolmentattheUniversityofMelbourne.Desirable:Experienceintestingchildrenwithneurodevelopmentaldisordersorequivalentclinicalexperience.8.PaininchildrenwithcerebralpalsyandotherdevelopmentaldisabilitiesA/ProfAdrienneHarveyadrienne.harvey@mcri.edu.au0393457540Painisincreasinglybeingrecognisedasasignificantissueforchildrenwithcerebralpalsy(CP)andotherdevelopmentaldisabilities,yetisunderidentifiedandconsequentlymanagedsuboptimallyinthispopulation.Inaddition,therearelimitationswithcurrentmethodsofmeasuringpaininchildrenwhoareunabletoself-reportduetocognitiveand/orcommunicationlimitations.ThisPhDprojectwillfocusontoolsthatidentifyandmeasurepainandvalidatingtheseinchildrenwithcerebralpalsyaswellasdevelopinginnovativemethodsusingtechnologytomeasurepaininchildrenwhoareunabletoself-report.Wehopetorecruitahighqualityalliedhealth,nursingormedicalprofessionalintothisPhDpositionandexperienceindisabilityisdesirable.9.PlacentalCordBloodCellTherapyinChildrenatHighRiskofHeartFailureA/ProfSalvatorePepesalvatore.pepe@mcri.edu.au0393454114Ourworkseekstoreducethehighriskofheartfailureanddeathfacedbychildrenwithsevereandcomplexheartdiseases.Babiesbornwithseverelymalformedheartandbloodvesselsthatareinadequatefornormalbloodcirculationundergoaseriesofcomplexheartoperations,thefirstisperformedonday2or3oflife(Norwoodprocedure).Evenaftersurgery,theheartisundergreatmetabolicandmechanicalstressasexcessivedemandsdonotallownormalheartmusclegrowthtosufficientlysupportbloodcirculationleadingtohighmortalityinthefirstyearoflife.Inotherchildrenwithheartfailureduetoheartmuscledamage(cardiomyopathy),surgicalimplantationofaventricularassistdevice(VAD,mechanicalpump)supportsheartfunction,alleviatingpressureandvolumeoverloadtoallowpotentialadaptiverepair,musclegrowth,improvedmusclefunctionandweaningfromthepump.Howevermanystillrequireahearttransplantordiewithin2yearsofdiagnosis.Fromourpreviousresearchandthatofothers,cordbloodstemcells(CBSC)have

beenfoundtostimulatenormalheartmusclegrowth,increasepumpingcapacity,andreduceinflammation,fibrosisandmetabolicstressaftersurgery.Inordertoapplythis,wehavedesignedasafewaytodirectlytreattheheartwithCBSCduringthecardiopulmonarybypasssurgerythatisemployedintheNorwoodandVADimplantationprocedures.Dependingonthequalificationsandinterests,anumberofresearchprojectsareavailableathonours,MastersorPhDlevel,involvinglaboratoryorclinicalbasedwork.Studentbackgroundandresearchinterestsareideallyinoneormoreareassuchas:physiology,immunology,haematology,genetics,biochemistry,pharmacology,surgery,veterinarymedicineormedicine.

Genetics10.InvestigatingthemolecularbasisofParkinson’sdiseaseusingnovelgeneticmodelsA/ProfPaulLockhartpaul.lockhart@mcri.edu.au0383416322Parkinson'sdiseaseisaprevalentneurodegenerativedisorderwithlargelyunknowncause.However,recentadvancementsingenomictechnologieshaveledtotheidentificationofover20genestobecausativeofaround10%ofParkinson'sdiseasecases.ThekeyneuropathologicalfeaturesofParkinson'sdiseaseincludealossofdopamineproducingneuronsandthepresenceofalpha-synucleincontainingproteinaggregatesinsurvivingneurons.WerecentlyidentifiedRAB39BasanovelgeneforParkinson'sdisease.RAB39Bhasaputativefunctioninintracellulartrafficking,andwehypothesisethatitplaysaroleintheregulationofalpha-synuclein.TheaimofthisprojectistocharacterisethefunctionofRAB39BandinvestigateitsroleinthepathogenicmechanismsunderlyingParkinson'sdisease.StudieswillutilisenewlydevelopedanduniqueinducedpluripotentstemcellandmousemodelswithmutationsinRAB39B.Inthisproject,thecandidatewillcharacterisethesenoveldiseasemodelsandperformvariousfunctionalstudies.Theywillbeabletodevelopskillsandexpertiseinawiderangeoftechniquesincludingstemcellculture,stemcelldifferentiation,mousehandling,andmousebehaviouraltesting.TheywillalsoutilisearangeofstandardmolecularandcellulartechniquessuchasrealtimePCR,westernblotting,immunostainingandmicroscopy.Overall,thisprojectwillinvolveperformingpreclinicalstudiesonnoveldiseasemodelstoimproveourunderstandingofthemolecularbasisofParkinson'sdiseaseandidentifypotentialtherapeutictargets.11.IdentifyingthegeneticcausesofbrainmalformationinchildrenA/ProfPaulLockhartpaul.lockhart@mcri.edu.au0383416322Thehumancortexisthesurfaceofthebrainthatenablesadvancedintellectualfunction.Itformsthroughaseriesofoverlappingstepsinvolvingneuronalproliferation,migrationanddifferentiation.Abnormalformationofthecortexcausesagroupofdisordersknownas

malformationsofcorticaldevelopment(MCD),whichcanresultinepilepsy,intellectualdisabilityandcerebralpalsy.ThereisconsiderableevidencethatgenemutationscauseMCD,buttodatefewofthegenesinvolvedhavebeenidentified.Thisprojectwillutilisemoderngenomictechnologies,includingwholeexomeandgenomesequencing,toidentifythegeneticbasisofMCD.ClosecollaborationwithneurosurgeonsandneurologistsattheRoyalChildren'sHospitalenablesuniqueaccesstotissuetoinvestigaterelevantdiseasemechanisms.Methodologywillincludesinglecelltranscriptomicsandproteomicanalysesofresectedbraintissue.Newlyidentifiedgeneswillbeinvestigatedinmodelsystems,includingpluripotentstemcellstodetermineunderlyingdiseasepathogenesis.Thesuccessfulapplicantwillworkcloselywithcliniciansandbioinformaticianswithinalargemultidisciplinaryteam.12.UnderstandingthemolecularbasisofCANVAS-anovelneurologicaldisordercausedbyanexpandedDNArepeatA/ProfPaulLockhartpaul.lockhart@mcri.edu.au0383416322RepeatexpansionscauseovertwentyneurogeneticdisordersofmajorclinicalDNArepeatexpansionmutationscauseovertwentyneurogeneticdisordersofmajorclinicalsignificancewhichcanpresentwithheterogenous,overlappingclinicalphenotypes.Discoveryofnovelexpansionsanddiagnostictestingofknownlocihasprovenextremelychallengingduetotherepeatsequencesbeingrefractorytostandardmoleculartechniques.Werecentlydeterminedthatanovelintronicpentanucleotiderepeatexpansiononchromosome4causestheneurogeneticdisordertermedcerebellarataxiawithneuropathyandvestibularareflexiasyndrome(CANVAS).Ourpreliminarystudiessuggesttheexpansionisthemostcommongeneticcauseofataxiainhumans.ThisprojectwillbeacomponentofalargerstudythataimstocharacterisetheCANVASrepeatmutationusingshortreadandlongreadgeneNextGenerationsequencingtechnologies.Itwillinvestigatepathogenicmechanismsunderlyingdiseaseutilisingmolecularandcellbiologytechniques,includingprimarycellandinducedpluripotentstemcellgenerationandcharacterisation.Thecandidatewillalsocontributetothegenediscoverycomponentofanongoingtrialtestingthediagnosticutilityofexpansionrepeatdetectioninnextgenerationsequencingdata.13.Developmentofnovelhumanstemcellderivedmodelsofbeta-propellerprotein-associatedneurodegenerationfordiseasemodellinganddrugscreeningA/ProfPaulLockhartpaul.lockhart@mcri.edu.au0383416322Beta-propellerProtein-AssociatedNeurodegeneration(BPAN)isarare,X-linkedneurologicaldisordercharacterisedbyintellectualdisability,seizuresandataxiainearlychildhood.TheconditionprogressesrapidlyleadingtodevelopmentofParkinsonism,dystoniaandcognitiveimpairmentinadolescence/earlyadulthood.ChildrenaffectedbyBPANdisplaybrainironaccumulationatanearlyage,leadingtoclassificationofBPANunderagroupof

disordersknownasneurodegenerationwithbrainironaccumulation(NBIA5).BPANiscausedbypathogenicvariantsintheWDR45genewhichencodestheWDrepeat-containingprotein45.Theproteinplaysanimportantroleinautophagy,abiochemicalmechanismthatregulatesdegradationandrecyclingofcellularcomponents.However,verylittleisknownaboutthecellulareffectsofvariantsinWDR45onthenervoussystemandhowitcausesBPAN.Hence,therearenodrugsavailablethatcancureorslowtheprogressionofBPAN.Inthisprojectwewillusepatient-derivedinducedpluripotentstemcells(iPSC)togeneratebraincellculturesinorderstudydisease-specificmechanismsandtestpotentialdrugtreatments.Thefirststepwillbetoexaminetheeffectsofpathogenicvariantsonelectrophysiological,biochemicalandmorphologicalpropertiesofdifferentiatedcells,withafocusonneurons.Drugstargetingrelevantpathways(e.g.autophagy,ironmetabolism,etc.)willbeusedtodeterminetheireffectivenessinmodulatingdiseasephenotypeintheneuron.ThiswillhelpestablishthevalidityofourculturemodelasavitalpreclinicaltoolforBPANdrugscreening.Theprospectivecandidatewillgettheopportunitytolearnarangeoflaboratorytechniquesincludingstemcellculturing,differentiationofstemcellsintoneurons,electrophysiology,immunocytochemistry,microscopy,drugscreeningassays,real-timeqPCRandwesternblotanalysis.14.DiscoveryofnewtreatmentsforbraindevelopmentdisorderslinkedtoepigeneticregulatorygenesA/ProfPaulLockhartpaul.lockhart@mcri.edu.au0383416322Thecerebralcortex-theouterlayerofthebrain-ishighlyexpandedinhumanscomparedtoothermammals,anditisthisuniquehumancharacteristicwhichisthoughttoaccountforourspeciesincreasedintellectualcapacity.Impairedcognition,asobservedinpeoplewithintellectualdisabilities,isoftenassociatedwithdefectsduringbraindevelopment.Duetoadvancesinhumangeneticsequencing,alargenumberofdevelopmentaldisordersassociatedwithintellectualdisabilitieshavebeinglinkedtogeneticmutationsinspecificgenes.Interestingly,alargenumberofthesegenesareinvolvedinepigeneticregulation-acellularprocesseswhichregulateswhichgenesareexpressedorsilencedthroughreversiblemodificationofhistonesorDNA.Corticaldevelopmentisahighlycomplexprocesswhichrequirestightandtimelycontrolovertranscriptionalprogrammesorchestratingexpressionandsilencingofamultitudeofgeneswhichgovernvariouscellularprocessesincludingproliferation,migrationandneuronaldifferentiation.Thereforemisfunctionofepigeneticgeneswhichregulatethesetranscriptionalprogrammesresultinfailuresinoneormoreofthesecellularprocessesduringcorticaldevelopmentandleadtolong-termintellectualdisability.Thebroadaimsofthisprojectareto:1.Modelhumancorticaldevelopmentinvitrousinghumanembryonicstemcell(hESC)andinducedpluripotentstemcells(iPSC)derivedfromintellectuallydisabledpatientsharbouringdeleteriousmutations2.Identifygene-dependentdeficitsduringcorticaldevelopment3.Runasmall-scaledrugscreenfortreatmentofthesegeneticdisorders.SuccessfulcandidateswillgenerateabatteryofgeneticallymodifiedhESCsusingCRISPR-Cas9mediatedgenedisruption,performinvitrocorticaldifferentiation,conductneuronalphenotypeanalysisusinglivecellconfocalimagingofgeneticallyencodedfluorescentreporters,assesselectrophysiologicalpropertiesof

neuronsusingMEAassays,conductbiochemicalanalysesofepigeneticmarkersalongwithperformingbasicmolecularbiologytechniquessuchascloning,genotypingPCR,westernblotandimmunocytochemistry.

InfectionandImmunity15.UnderstandingthecauseofHumanpapillomavirus(HPV)-negativecervicalcancersinAustralianwomen.DrGeraldMurraygerald.murray@mcri.edu.auBackground:Cervicalcancerislistedasthefourthmostcommontumourinwomenworldwide.WiththevastmajorityofthesecancersattributedtoHPVinfection,manycountriesareusingprophylacticHPVvaccinestopreventinfection,aswellasHPVDNAdetectionassaysastheprimaryscreeningtoolreplacingPapcytology.However,thisscreeningmethodmaymissasmallpercentageofcervicalcancercasesseeminglynotcausedbyHPV.IdentificationofspecificDNAbasedtargetsareneededtocapturethissmallpercentageofcervicalcancercases.TheProject:CurrentlyHPVnegativecervicalcancersareattributedtoapprox.7%ofallcervicalcancerswiththeaetiologicalagentcurrentlyunknown.PreviousstudieshaveidentifiedthataproportionoftheseHPVnegativecancersdocontainHPVsequencesofeithergenotypesnotcommonlytestedfororknowngenotypesthatcontainDNAmutationsintheL1/L2andE6/E7genes,commonlyusedasPCRtargets.TheprojectispartofacollaborationwithresearchinstitutesandhospitalsacrosstheEasterncoastofAustraliaandinvolvestheuseoflaboratorybasedmoleculartechniquesandbioinformaticanalysisofnextgenerationsequencingdata,toidentifytheaetiologicalagentfortheseHPVnegativecancers.ProjectOutcomes:TheprojectaimstoidentifyHPVnegativecancersamongallrecentlydiagnosedcervicalcancersinAustralia.Uncovertheunknowncausesfortheunderlyingneoplasiaandusethistoaidintheexpansionofcurrentmoleculartargets.FinancialsupportAninitialfirstyearPhDscholarshipisavailableforthesuccessfulapplicanttothevalueof$33,092.ThesuccessfulapplicantwillalsobeencouragedtoapplyforanAustralianResearchTrainingScholarshipfortheremainderoftheirproject.16.ImmunemechanismsofpeanutallergyremissionDrMimiTangmimi.tang@rch.org.auFoodallergiesareamajorhealthburdenglobally,andAustraliahasthehighestreportedratesoffoodallergyintheworld.Thereiscurrentlynocuresoresearchhasfocusedonidentifyingapproachestoredirectallergen-specificimmuneresponsesawayfromallergytowardsatolerantstate,whichcansupportclinicalremissionofallergy.Severaltherapiesunderinvestigationcaninduceremission,whichmaybetransientorlonglasting.Theimmunechangesoflong-lastingremissionareunknown;understandingthekeyfactorsthat

leadtolong-lastingremissionwillenabledevelopmentofeffectivelong-termtreatmentsforfoodallergy.Wehavebeeninvestigatingacombinationtreatment,ProbioticandPeanutOralImmunotherapy(PPOIT),whichhasbeenshowntoinducelong-lastingremissionthatpersiststo4yearspost-treatment.Bycontrast,publishedreportsofpeanutoralimmunotherapy(OIT)withoutimmunologicaladjuvantsuggestthatOIT-inducedremissionmaybeshort-lived,withtwothirds(67%)oftreatmentresponderslosingtheirremissionstateby12monthsposttreatment.Theaimofthisprojectistouseacombinationofgeneexpressionandflowcytometryapproachestounderstandtheimmunemechanismsinvolvedinretrainingtheallergicresponsetowardslong-lastingremissionofpeanutallergy.Geneexpressionandflowcytometrydatawillbegeneratedonimmunecellsbeforeandafterinterventionin1)patientswhoachieveremissionofpeanutallergyremissionfollowingPPOITtreatment2)patientswhoachieveremissionofpeanutallergyfollowingstandardOIT3)patientswhoremainallergictopeanutfollowingplacebotreatment.Findingswillprovidecluesofkeyimmunefactorsthatdrivelastingremissionofallergycomparedtoremissionthatislostovertime,whichmayinturnleadtodevelopmentofmoreeffectivelong-termtreatmentsforfoodallergy.17.ThecardiometaboliclegacyofSARS-CoV-2inlongitudinaladolescentsProfDavidBurgnerdavid.burgner@mcri.edu.au0399366730Summary:SARS-CoV-2isarespiratoryvirusthathasn'treadthetextbookonhowitshouldbehave;acuteCOVID-19appearstobeadiseaseofbloodvesselsasmuchasoftherespiratorytract.Thereisalsoconcernregardingthelong-termeffectsofacuteSARS-COv-2infection,withincreasingreportsofprotractedsymptoms('longCOVID')andincreasedriskofcardiovasculardisease(CVD).ThisprojectwilladdresstheeffectsofCOVID-19onthecardiovascularandmetabolic(cardiometabolic)healthofadolescents.ThisexcitinginnovativeprojectwillfocusonthenewlyestablishedYoungLivescohortofover1000population-representativeadolescents,whowillhaveadetailednon-invasiveassessmentsandextensivemetabolomicprofilingatrecruitmentandagain12monthslater.Thefindingswillhaveimmediatetranslationalimportanceandwillinformprevention,interventionsandpolicy.ProjectDescription:Thesuccessfulapplicantwilljoinafriendly,dynamicmultidisciplinaryteam(includingotherPhDstudentsworkingontheimmunologicalandpsychosocialaspectsoftheYoungLivescohort,whoareacademicpaediatricians,researchscientists,andepidemiologists.Thecandidatewillanalysecardiometabolicandlaboratorydatacollectedatrecruitment,andundertaketrainingtoparticipateintheongoingassessmentoftheparticipants.Theprojectcombineshands-onclinicalresearch,laboratorywork,anddataanalysisandinterpretation.Theprojectwouldsuitaclinician(e.g.paediatrician,infectiousdiseases,cardiologist,endocrinologist)orascientistwithaninterestandsomecontentknowledgeintheseareas.Fulltrainingofcardiometabolicassessmentsandotherkeyskillswillbegiven.Excellentpeopleskillsareessentialandsomeexperienceofdatamanagementandstatisticalanalysiswouldbebeneficial.Thesuccessfulcandidateisexpectedtobecompetitiveforownscholarshipfunding(APAorsimilar).Top-upfundingmaybeavailable.

18.Definingthemechanismsthatunderpinthebeneficialoff-targeteffectsofBCGProfNigelCurtisNigel.Curtis@rch.org.auInadditiontoprotectingagainstitstargetdisease,tuberculosis,theBacillusCalmette-Guérin(BCG)hasbeneficialoff-target('heterologous'or'non-specific')effectsonhumanhealthincludingreducingallcauseinfantmortality,likelybyprotectingagainstnon-mycobacterialinfectiousdiseases.ThisprotectionisproposedtoresultfromtheimmunomodulatoryeffectsofBCG.Ourteamhasestablishedtworandomisedcontrolledtrials(RCTs)investigatingwhetherBCGprotectsagainstnon-mycobacterialdiseases:-MelbourneInfantStudy:BCGforAllergyandInfectionReduction(MISBAIR):ourRCTofneonatalBCGvaccinationin>1200childreninMelbournetodetermineifBCGprotectsagainstallergicdisease,eczema,asthmaandinfections.TheBRACEtrial:ourinternationalRCTof>10,000healthcareworkerstodetermineifBCGvaccinationreducestheimpactofCOVID-19andotherrespiratorydiseases.ThisprojectwillusesamplesfromparticipantsinoneorbothoftheseRCTstocharacteriseBCG-inducedchangesintheimmunesystem.Thisprojectwilluseacombinationofinvitrostimulation,flowcytometry,multiplexcytokineassays,epigeneticanalysisandgeneexpression.ThefindingsofthisprojectwillprovideimportantinsightsintotheimmunomodulatoryeffectsofBCGandtheassociationsbetweenthesechangesandthebeneficialclinicaleffectsofthisvaccine.19.UnravellingtheInflammatorySignaturesofPaediatricRespiratoryDiseaseDrMelanieNeelandmelanie.neeland@mcri.edu.auInflammationisakeyaspectofthepathophysiologyofmanycommonpaediatricrespiratorydiseases,butverylittleisknownabouttheexactinflammatorypathwaysthatdefinedifferentdiseases.Abetterunderstandingoftheinflammatorysignatureofdifferentpaediatricrespiratorydiseaseswouldhelptoidentifynoveltherapeutictargetsandpredictivebiomarkers.InthisPhDyouwillhavetheopportunitytoworkaspartofalargerstudythatisaimingtodefinetheinflammatorysignaturesofcommondiseasessuchasasthma/wheeze,acutelowerrespiratorytractinfections,lungdiseaseofprematurityandbronchiectasis.Whatisuniqueandworldleadingaboutthisprojectistheuseoftissuespecificsamples(bronchoalveolarlavageandbronchialbrushings).TheexactfocusofthePhDcanbedetermined,butbroadlyspeakingyourPhDwouldinvolvelaboratoryexperiencewithtechniquessuchasflowcytometryandsinglecellRNAsequencing,andbioinformaticanalysisusingmulti-omicdatasets.Theidealcandidatewouldhavelaboratoryexperience,ideallywithflowcytometryorRNAsequencing,andbekeentoundertakeresearchthathasastrongclinicalcomponent.

PopulationHealth20.PredictorsofinfectionandclinicalseveritywithSARS-CoV-2inextantlongitudinalLifeCoursepopulationcohortsofchildrenandtheirhousehold/familycontactsA/ProfKirstenPerrettkirsten.perrett@mcri.edu.auSummary:ThisprojectwillusedatafromtheCOVID-ImmuneandYoungLivescohortstudieswhichharnesstheMCRI'suniquepopulationcohortsofchildrentoinvestigatewhetherpre-COVIDimmunephenotypesandbiomarkerspredictsusceptibilitytoandseverityofSARS-CoV-2infection.Inaddition,thisprojectofferstheopportunitytofurtherunderstandtheclinicalfeatures,naturalhistory,transmissiondynamicsandlong-termeffects/legacyofSARS-CoV-2infectioninchildren,adolescentsandyoungadults.Thefindingswillhaveimmediatetranslationalimportanceandwillinformprevention,interventionsandpolicy.ProjectDescription:COVID-19epidemiologyandpathophysiologyareunprecedentedbutpoorlyunderstood,hamperingshort-andlong-termmanagement.Infection-related,dysregulatedimmuneresponsesarecentralandlikelyunderpintheincreasinglyrecognisedlong-termimpacts.AstrikingfeatureofthecurrentCOVID-19pandemicistherelativelylowincidenceofsymptomaticinfectionandmilderdiseaseinchildren.Thisismarkedlydifferenttoalmosteveryotherinfectiousdisease,particularlythoseduetoviruses.Keyscientificquestionsaretherefore,whychildrenarelesssusceptibletoinfectionand,ifinfected,whytheclinicalseverityismuchlessthaninadults,whoisatriskandwhatistheimmunologicallegacyofinfection.Thisprojectwillinvestigatepre-pandemicimmunedataandbiosamplesfromupto3500children,adolescentsandyoungadultsfrom4ofMCRI'suniquepopulationcohortsandfollowthemforsymptoms/signsofCOVID-19andseroconversion.Inaddition,comprehensiveimmunephenotypingwillbedoneatbaselineand12monthsintheadolescent/youngadultYoungLivescohort(n=1000)toinvestigatetheimmunologicallegacyofCOVID-19infectiontounderstandearlyevidenceofadversechangesinimmuneresponsesandinflammation.21.Takingplacentatoscale:ThepopulationburdenofdisorderedplacentationandplacentalfunctionProfMelissaWakemelissa.wake@mcri.edu.auTheplacentaregulatesahealthypregnancy.Thepopulationburdenofdisorderedplacentationandfunctionisunquantifiedbutpotentiallyimmense.ThishighlynovelPhDtakesplacentalresearchtoscale,developinginnovativehigh-throughputplacentalimagingandsamplingwithinthe'GenerationVictoria'cohort,targetingall160,000Victorianbirthsovertwoyearsandall70birthinghospitals.Initiallyfocusingontheplacentalpathophysiologyofthegreatobstetricsyndromes,theresourceonceestablishedcanlaterquantifyplacentalrolesinmaternal,fetal,childhood,adultandtransgenerationalhealth.ThelandmarkGenVthusoffersimmenseopportunitiestoestablishacareerandleadershipintransformativepregnancyandnewbornresearch.

NonLab-basedprojects

CellBiology22.MetabolicreprogrammingofthefailingheartDrAlejandroHidalgo-Gonzalezalejandro.hidalgogon@mcri.edu.au0383416484Afteraheartattacktheheartmuscleundergoesmajorcellularchangesinordertopreservefunctionandremainviable.Thesechangesarebelievedtobean'adaptive'mechanismtoallowtheheartmuscletocontinuetopumpenoughbloodtotherestofthebody.Intheshortterm,thesecellularchangessuccessfullymaintainfunctionbutfailuretoreturntonormalphysiologyleadstocellulardysfunction.Mostofthesephysiologicalchangesaffectthemitochondria'scapacitytoproduceenergyandregenerate.Accumulationofdysfunctionalmitochondriabecomesasourceoftoxicsubproductsthatsignificantlycontributestocelldeath.Themitochondrionhasbeentermedthepowerhouseofthecell,consideringitgenerateslargequantitiesofenergy.Duetoitsrole,itisimperativethatmitochondrialhomeostasisismaintainedtoguaranteeadequateenergygenerationforcardiacfunctionandtoreducetheproductionoftoxiccellularsubproducts.Mitochondrialqualitycontrolandrecyclingisorchestratedbyamultiproteincomplexthatallowsidentificationanddegradationofdamagedmitochondria.Modulationofoneormultiplemembersofthiscomplexcouldenhancemitochondrialregenerationandhavepotentialforthetreatmentofdiseasedcardiomyocytes.Todate,mitochondrialregenerationhasnotbeenexploredasatherapyforheartfailure.Inthisproposal,wewilltakeadvantageofour"heartattack"modelfromhumanpluripotentstemcellstovalidatefactorsformitochondrialregenerationandimprovecellsurvival,reducecardiacmusclelossandincreasecontractility.Thisprojectwillinvolvethegenerationofhumanheartcellsfromstemcells,cellculture,immunohistochemistryandconfocalimaging.

ClinicalSciences23.Long-termimpactofmoderateandlatepretermbirth:effectsonneurodevelopment,braindevelopmentandrespiratoryhealthatschoolageProfJeanieCheongjeanie.cheong@thewomens.org.au0383453771TheVictorianInfantBrainStudiesgroupatTheMurdochChildren'sResearchInstituteisseekingaPhDstudenttojointheirteamonaprojectinvestigatingtheimpactofmoderate-latepreterm(MLP;32to<37weeks'gestation)birthonneurodevelopment,braindevelopment,andrespiratoryhealthat9yearsofage.ThemajorityofpretermbirthsareattributedtoMLPbirths,andthereisagrowingevidence-basedemonstratingthatchildren

bornMLPexperiencemoreadverseoutcomesinearlychildhoodthantheirterm-bornpeers.Specifically,childrenbornMLPexperienceincreasedrespiratorymorbidityininfancyandearlychildhoodthantheirterm-bornpeers.OurpreviousresearchhasalsofoundthatinfantsbornMLPhavesmallerandlessmaturebrainsthanterm-borninfantsatterm-equivalentage,althoughlessisknownaboutbrainchangesovertimeinthispopulation.Withinthelargerproject,childreninthestudyarewearingatri-axialaccelerometertomeasurephysicalactivity,sedentarybehaviourandsleeppatternsforoneweek,aswellascompletingaself-reportedphysicalactivityquestionnaire.ThePhDstudentwillinvestigateoneofthefollowingareasinrelationtotheseactivitydata:1)Theassociationbetweenphysicalactivitylevelsandbrainfunctionin9-year-oldchildrenbornMLPcomparedwithterm-borncontrols.ChildrenareundergoingbrainMRI,andthePhDstudentwillbesupportedbyexpertsintheareaofneuroimaging.2)Theassociationbetweenphysicalactivitylevelsandrespiratoryfunctionin9-year-oldchildrenbornMLPcomparedwithterm-borncontrols.Theprojectcontainsrichdataconcerningrespiratoryhealth,aschildrenarecompletinglungfunctiontestsandwearecollectingdataonrespiratorysymptomsanddiagnoses.3)Theassociationsbetweensleepdurationandqualityandcognitive/behaviouraloutcomesin9-year-oldchildrenbornMLPcomparedwithterm-borncontrols.Wearecollectingdetailedneuropsychologicaldata,suchasIQ,memoryandacademicachievement,alongsidedataconcerningbehaviouralproblems.24.NeuropsychologicalprofileofchildrenwithspeechdisorderProfAngelaMorganangela.morgan@mcri.edu.au0383416458Childhoodspeechdisordersarecommon,affecting1in20preschoolchildreninthegeneralpopulation.Yetmostofthesechildrenpresentwithmildarticulationorphonologicaldisordersthattypicallyresolvewithorwithoutintervention.Bycontrast,approximately1in1,000patientspresentwithapersistentandlesstractablespeechdisorderknownaschildhoodapraxiaofspeech(CAS).ThreecoresymptomssupportaCASdiagnosis:includinginconsistenterrorsonconsonantsandvowels;lengthenedanddisruptedcoarticulatorytransitionsbetweensoundsandsyllables;andinappropriateprosody.Lifelongimpairmentisseen,withpsychosocialimpact,literacydeficits,andrestrictededucationalandemploymentoutcomes.WhyisCASsomuchmorepersistentthanotherspeechconditions?Increasingevidencehasshownageneticbasisforupto1in3childrenwithCAS.Novelmolecularpathwayshavealsobeenrevealed,indicatingarolefortranscriptionaldysregulation.ThismechanismisassociatedwithalteredbraindevelopmentwhichresultsintheCASsymptomatology,alongwithothercommonlyshareddeficitssuchasimpairedmotorskilldevelopment.Todate,fewstudieshaveexaminedneuropsychologicalstrengthsandchallengesinchildrenwithCAS.Agreaterunderstandingofcognitivecontributionstothecondition,combinedwithnewgenomicdata,willleadtomoretargetedtherapeuticinterventionsandhelptoexplainthemechanismswhichleadtothissymptomprofile.OurteamhasanexcitingPhDopportunityforaprojectexaminingcognitivecontributionsinCASassociatedwithourspeechgeneticsclinicattheRoyalChildren'sHospital.

25.MeasuringchildandfamilycentredoutcomesfollowingspinalsurgeryforchildrenwithneuromuscularscoliosisA/ProfAdrienneHarveyadrienne.harvey@mcri.edu.au0393457540Scoliosisiscommoninchildrenwithcerebralpalsyandotherdevelopmentaldisabilitieswhohavesignificantgrossmotorimpairmentandimpactssignificantlyonthechild'swellbeing,qualityoflifeandparticipation.Spinalsurgeryisthedefinitivetreatmentforprogressivescoliosis,howeveritcomeswithamoderatelyhighcomplicationrate.Thereissomeevidencethatsurgeryiseffectiveforreducingthedeformity,butinsufficientevidencethatitimprovesfunctionaloutcomes,caregiveroutcomes,andqualityoflife.Thisprojectfocusesondevelopingrobustmethodstomeasurechildandfamily-centredoutcomesfollowingspinalsurgeryforchildrenwithneuromuscularscoliosis.Theprojectwillinvolvebothquantitativeandqualitativemethodologies.Wehopetorecruitahighqualityalliedhealth,nursingormedicalprofessionalintothisPhDpositionandexperienceindisabilityisdesirable.26.ComprehensiveclinicalphenotypingofindividualswithstutteringProfAngelaMorganangela.morgan@mcri.edu.au0383416458Stutteringischaracterizedbydysfluentspeech,whichmayhaveaprofoundeffectonanindividual'ssocialandmentalwellbeing.Upto11%ofchildrenbeginstutteringby4yearsofage.Approximatelyone-thirdofaffectedpreschoolerswillgoontodevelopapersistentstutter.Stutteringinterventionsareeffectiveforsomechildreninthepreschoolyears;yettherearelesseffectivetreatmentsforolderchildren,adolescentsandadults.Further,itisnotpossibletopredictwhowilldeveloppersistentstuttering.Understandingthegeneticbasesofstutteringwillprovideinsightsintotheunderlyingbiology,potentiallyleadingtostratificationofstutteringintoclinicallyrelevantsubtypesandmoretargetedtherapies.Estimatesfortheheritabilityofstutteringrangefrom0.4-0.8,indicatingastronggeneticinfluence.Family-basedstudieshaveimplicatedrarevariantsin4genes,howeveritisnotclearwhetherthesegenesarealsorelevanttostutteringinthegeneralpopulation.Wehypothesizethatcommongeneticvariationmakesasubstantialcontributiontotheriskofstutteringandproposethatthisismosteffectivelyinvestigatedbyundertakingagenome-wideassociationstudy(GWAS),usingalargepopulation-basedsampleofpeoplewithstuttering.OurAustralianteamattheWEHI,MCRI,QIMRandUniversityofMelbourneareleadinganinternationalGWASconsortiumtoidentifygeneticlociandmolecularpathwaysimportanttostuttering.Aspartofthiseffort,wehavealreadycollectedspeechdataonalmost1000individualswithstuttering,thelargestcohortofitsnaturetodate,withdatacollectionongoing.Despitedecadesofinterestinthesymptomatologyofstuttering,existingdeepphenotypingstudiesarelargelylimitedtosmallhighlybiasedclinicalsamples.ThisPhDprojectwillfocusoncomprehensiveclinicalphenotypingofindividualswithstutteringrecruitedtoourGWASstudy.Ourgenotype-phenotypeapproachwillallowustobeginto

disentanglethebiologicalpathwaysandgenenetworksthatunderliestuttering,themostcommonspeechdisorder.27.MentalhealthandparticipationoutcomesforchildrenandyouthwithcerebralpalsyProfChristineImmschristine.imms@unimelb.edu.au0399533404Mentalhealthproblemsandparticipationrestrictionsarefrequentlyreportedforchildrenwithdisabilities.Thereislittleinformationonthelong-termrelationshipsbetweenmentalhealthandparticipationinthepresenceofchild-onsetdisability,orabouthowmentalhealthisaffectedbyrehabilitationservicesprovidedforthesechildrenandfamilies.ThiscollaborativeprogramofresearchisbeingledbyaSwedishresearchteam(Prof.MatsGranlund)andwillinvestigaterelationsbetweenparticipationandfactorsaffectingparticipationwithafocusonmentalhealthandservicesprovidedtochildrenwithdisabilitieswhohavementalhealthproblems.Theprogramisintwoparts:(i)childrenwillbefollowedfor5yearstocollectlong-termoutcomedataonparticipationandmentalhealth;and(ii)children,parentsandprofessionalswillcollaboratetodevelopandevaluatemethodsforinvolvingchildrenandparentsinthe(re)habilitationinterventionprocess.ThereisanopportunityforanAustraliandoctoralscholarship(withstipend)withinthisprogramofworkwithaparticularfocusonoutcomesforadolescentsandyoungadultswithcerebralpalsy.Wehopetorecruitahigh-qualityalliedhealth,psychologyormedicalprofessionalintothisPhDpositionandexperienceindisabilityisdesirable.28.SupportingyoungpeoplewithcomplexdisabilitytoparticipateinimportantlifesituationsProfChristineImmschristine.imms@unimelb.edu.au0399533404Beingabletoattendandbeinvolvedinavarietyofactivitiesandmeaningfullifesituationsisastrongcontributortolong-termhealthandwellbeing.Youngpeoplewhohaveintellectualimpairments,withorwithoutassociatedphysicalimpairments,oftenexperiencerestrictionsintheirparticipationincommunitylife,includingemploymentandrecreation.Programsarebeingdesignedthataimtosupportthelearningofskillsneededtoeffectivelynavigatetheenvironmentsinwhichcommunityactivitiesoccur.Developmentofparticipation-supportingskills(e.g.settingparticipatorygoals,determiningrelevantbarriersandsupports,gainingself-advocacyskills)iscriticaltoenablingincreasedparticipation.ThisworksitswithintheNHMRCfundedCentreforResearchExcellenceCPAchieveprogram,andistargetedtowardsinvestigatingthefeasibility,effectandpotentialforup-scalingofaparticipation-focusedintervention,suitableforthosewithintellectualimpairments.Thereisanopportunityforadoctoralstudentwithinthisprogramofwork.Wehopetorecruitahigh-qualityalliedhealth,psychologyoreducationalprofessionalintothisPhDpositionandexperienceindisabilityisdesirable.

29.Understandinganddefiningsupportivehealth/NDISserviceenvironmentsProfChristineImmschristine.imms@unimelb.edu.au0399533404Asyoungpeoplewithlongtermhealthconditionstransitionthroughadolescenceandintoadulthoodtheybecomemoreresponsibleforhowtheynavigatetheirenvironmentstogainaccessto,andtoparticipatein,arangeofimportantactivities.Oneenvironmentknowntobeofgreatimportanceandasignificantchallenge,isthenavigationofhealthanddisabilityserviceprovisionintheadultserviceprovisionsector.CurrentlywehavelimitedknowledgeabouthowparentsandyoungpeoplewithcerebralpalsyinAustraliaworktogethertonavigatethisaspectoftheyoungperson'stransitiontoadulthood.Weknowthatsomeyoungadultswithcerebralplaywilltransitionsuccessfullywiththeirusualsupports,somewillalwaysneedsignificantassistance,andweanticipateathirdgroupwhohavethecapacitytodevelopself-managementskillsbutwhostruggletodoso.Thegoalofthisprogramofworkistoexploretheimpactofthehealthanddisabilityserviceenvironments,thequalityoftheindividuals'supportnetworksontheiraccessanduseofservicesacrosssettings.ThisworksitswithintheNHMRCfundedCentreforResearchExcellenceCPAchieveprogram,andaimstoidentifymodifiablebarriersformoreeffectivehealthanddisabilityservicestransitionforyoungadultswithcerebralpalsy.Thereisanopportunityforadoctoralstudentwithinthisprogramofwork.Wehopetorecruitahigh-qualityalliedhealth,nursing,psychologyormedicalprofessionalintothisPhDpositionandexperienceindisabilityisdesirable.30.Adaptanevidence-basedhealthylifestyleprogramtoanAustraliancontextProfPrueMorganprue.morgan@monash.eduYoungpeoplewithdevelopmentaldisabilitymayexperiencelongtermsocial,physicalandmentalhealthissuesthatimpactontheirlifeparticipationandabilitytoliveahealthylife.Thetransitionperiodfromchildhoodtoadulthoodprovidesanopportunitytodevelopself-managementskillsandassumegreaterindependence,withorwithoutsomeassistance.However,wedon'tknowhowbesttosupportthedevelopmentofself-efficacy,healthliteracyandparticipationskillsinyoungpeoplewithcerebralpalsyinAustralia,toenablethemtomakegoodchoicesandliveahealthylife.Therearesome'lifestyleprograms'availableinothercountries,butwedon'tknowiftheywillmeettheneedsofyoungpeoplewithcerebralpalsylivinginAustralia.Thegoalofthisprogramofresearchistoidentifywhatinformationyoungpeoplewithcerebralpalsyneed,andhowbesttoprovidethiseducationinorderforthemtoliveahealthyandhappylife.ThisworksitswithintheNHMRCfundedCentreforResearchExcellence'CP-Achieve'program,andaimstodevelopandtestaconsumer-informedevidence-basedhealthylifestyleprogram.Thereisanopportunityforadoctoralstudentwithinthisprogramofwork.Wehopetorecruitahigh-qualityalliedhealth,nursing,psychologyormedicalprofessionalintothisPhDpositionandexperienceindisabilityisdesirable.

31.OptimisinguseofeverydaytechnologyforchildrenandadolescentswithacquiredbraininjuryDrSarahKnightsarah.knight@mcri.edu.au0399366577Acquiredbraininjury(ABI)isacommoncauseofchildhooddisability.Inchildrenandadolescents,amongthemostcommoncausesofABIaretraumaticbraininjury,stroke,infection,tumour,hypoxia,andencephalitis.ManychildrenwithABIexperiencelong-termcognitive,communication,physicalandsocialdifficultiesthatareassociatedwithreducedindependence,participationandoverallqualityoflife.Everydaytechnologies,suchassmartphonesandtablets,havegreatpotentialaspopular,multifunctiontoolstosupportindependenceandparticipationfollowingacquiredbraininjury(ABI).AlmostallAustralianadolescentsandtwo-thirdsofprimaryschoolagedchildrennowowntheirowntabletorsmartphone.However,thereisevidencethateverydaytechnologiessuchastheseareunder-utilisedinrehabilitationcontextsdespitegrowingevidencetosupporttheiruseaseffectiveassistivedevicesacrossarangeofdisabilities.Thereisadistinctneedtobetterunderstandcurrentpatternsofuse,aswellashealthprofessionalandcaregiverfamiliarity,skill,knowledgeandconfidenceinsupportingchildrenandadolescentswithABItousetechnologytooptimiseindependenceandparticipationineverydaylife.Thisprojectwilluseamixedmethodsapproachto:(1)betterunderstandhowchildrenandadolescentswithABIuseeverydaytechnologies,(2)identifythefacilitatorsandbarrierstosupportingtheuseofeverydaytechnologiesinarehabilitationcontext,and(3)examineifandhowrehabilitationprofessionalsandcaregiverssupportandteachchildrentouseofeverydaytechnologyintheirhome,schoolandcommunityaspartoftheirrehabilitation.Thisdatawillbeusedintheco-designofahealthprofessionalandfamilytrainingpackagetooptimisetheuseofeverydaytechnologyforchildrenandadolescentswithABI.ThisprojectwillfitunderthebroaderumbrellaoftheMCRIABIintegratedknowledgetranslationprogram.Studentswouldneedastrongacademictrackrecordandinterestinrehabilitationandtechnologyisdesirable.32.AssessmentandmanagementoffatiguefollowingpaediatricacquiredbraininjuryDrSarahKnightsarah.knight@mcri.edu.au0399366577Acquiredbraininjury(ABI)isdefinedasanybraininsultthatoccursafterbirth.Inchildrenandadolescents,amongthemostcommoncausesofABIaretraumaticbraininjury,stroke,infection,tumour,hypoxia,andencephalitis.Fatigueisafrequentlyreportedsequelaeofacquiredbraininjury(ABI),andcannegativelyimpactonachild'sparticipationineverydaylife.InchildhoodABI,fatigueisassociatedwithpooracademicachievement,limitedphysicalactivity,andsocialandemotionalproblems.Theeffectivemanagementoffatigueisaclinicalpriorityforpaediatricrehabilitationservices.However,thereisminimalresearchthatfocusesonunderstandingthebestapproachtosupportingchildrenandfamiliesto

managefatigue.ThisstudywilluseamixedmethodsdesigntoexamineexistingapproachestotheassessmentandmanagementoffatigueinchildrenwithABIfromtheperspectivesofchildren,familiesandpaediatricrehabilitationprofessionals.Thisdatawillbeusedintheco-designofafatiguemanagementprogramforchildrenwithABI.ThisprojectwillfitunderthebroaderumbrellaoftheMCRIABIintegratedknowledgetranslationprogram.Studentswouldneedastrongacademictrackrecordandinterestsinrehabilitation.ThisprojectwillbebasedwithintheNeurodisabilityandRehabilitationgroupattheMurdochChildren'sResearchInstituteandtheVictorianPaediatricRehabilitationServicewherethesuccessfulcandidatewillbesupportedbyahighlyexperiencedclinicalresearchteam.

Genetics33.RareDiseasesNow-GreatcareforrareA/ProfTiongTantiong.tan@vcgs.org.au0399366576Rarediseasesindividuallyaffectfewerthan1in2,000births,butcollectivelytheyarecommon-over5,000patientsareseenontheMelbourneChildren'scampusforrarediseasediagnosiseachyear.Nationally,morethan15,000Australianchildrenborneachyearwillhaveashortenedlifespanorexperiencedisabilityduetoararedisease.About80%ofrarediseasesareofgeneticoriginandtheyareestimatedtocause35%ofdeathsinchildrenbeforeoneyearofage,andupto20%ofpaediatrichospitaladmissionsworldwide.Despitegenomictesting,themajorityofchildrenwithararediseasedonotreceiveagenomicdiagnosisandevenfewerreceiveimpactfulinterventions.Atthebeginningof2020,theMCRIRareDiseaseFlagshipreceivedalmost$2MoverthreeyearsfromtheRoyalChildren'sHospitalFoundationforRareDiseasesNow(RDNow),anexcitinginitiativetodelivergenomicdiagnosesandprecise,personalisedcaretoRCHfamilies.DrawingontheresearchandclinicalexpertiseattheMCRIandVCGS,RDNowwillengagewithnon-geneticsspecialistswithinRCHtoestablishacampus-wideframeworkforundiagnosedchildrentohavethebestchanceofreceivingadiagnosisandtoaccessthelatestclinicaltrialsandtreatments.RDNowseeksanenthusiasticPhDstudentpassionateaboutrarediseasesforaprojectexaminingakeyquestionintherarediseasefield.Scopeofpotentialprojectsincludesnovelgenomictestingmethodsandanalysisstrategies,developingpathwaysforregistriestostudythenaturalhistoryofararediseaseandlinkingtoclinicaltrialsandtherapies.ThestudentwilladdressthesechallengesbybeingamemberoftheRDNowteamtodevelopsystemstoimproveaccesstorarediseasediagnosis,linkingnewdiscoveriestonaturalhistorystudiesandclinicaltrials,andfacilitatethebroadeningofgenomicexpertiseintomultipleRCHDepartments.Thisprojectwouldsuitanindividualwithapaediatricclinicalbackgroundorundergraduate,postgraduate,orvocationalgenetics/genomicsexperience.Akeeninterestinrarediseasesisessential.Apublicationtrackrecordinrarediseasesorgenomicsishighlydesirable.ThesuccessfulapplicantwilldevelopcollaborativerelationshipswithRCHclinicians,MCRIscientists,theVCGSlaboratoryteamandbioinformaticians.

34.ImplementationconsiderationsforanationalprogramforexpandedreproductivecarrierscreeningDrAlisonArchibaldAlison.archibald@vcgs.org.auBackground:Publicly-fundedgeneticcarrierscreeninginAustraliaiscurrentlylimitedtoindividualswithafamilyhistoryofageneticcondition,andparticularethnicgroups.MostAustraliancoupleswhohavechildrenaffectedbysevererecessivegeneticconditionsarenotawareoftheirhighchanceofhavinganaffectedchild.InMay2018,FederalHealthMinisterGregHuntannounced$20MfundingfromtheMedicalResearchFutureFund(MRFF)forMackenzie'sMission(MM),aresearchstudytoinvestigatehowbesttodeliverafree,easilyaccessibleRGCSprograminAustraliaforallcoupleswhowishtouseit.MMwillscreen10,000couplesfortheirchanceofhavingachildwithaconditionduetomutation(s)inabout1300genes.TheaimsoftheMMcarrierscreeningprojectareto:•DevelopandtestprocessesforRGCSasprovidedbyMM•EvaluatetheuptakeofRGCS,frequencyofincreased-riskcouplesandtheirreproductivedecisions•EvaluatetheimplementationofRGCS•Evaluatethescreeningexperienceofcouplesincluding

▪psychosocialimpacts,▪implementationchallenges,▪ethicalissuesand▪healtheconomicimplications

PhDprojectdesign:ThePhDstudentwilltakeresponsibilityforamixed-methods,longitudinalanalysisoftheMMprogramwithafocusonimplementationfromtheperspectiveofcoupleswhoparticipateinthestudy.Thiswillincludeintrinsicandextrinsicinfluencesoncouples'decision-makingaboutscreeningandaboutfuturereproductivechoices.ThecandidatewillworkcollaborativelyacrosstheMMresearchstreamsgatheringdatatosupporttheirPhD.Quantitativedata(drawingonimplementationandevaluationframeworksandexistingscalesincludingthemulti-dimensionalmeasureofinformedchoice,deliberation,decisionalconflictandregret)willbecollectedandanalysedtoassesscongruenceofknowledge,attitudeandbehaviourtoevaluateinformeddecision-making.ThestudentwillanalyserelevantquantitativedatacollectedinsurveysfromcouplescompletedbeforeandafterscreeningprovidedthroughtheMMprogram.Thestudentwillcollectandanalysequalitativedataininterviewswithpurposivelyselectedindividualsbeforeandafterscreeningtoexploreandexplaindecision-making.TheoutcomesofthisPhDwillincludeanevaluationoftheMMprogramfromtheperspectiveofparticipatingcouples,recommendationstoaddressbarriersandenablersidentifiedandparticipationindevelopmentofanimplementationplanforanationwidescreeningprogram.Theprojectmayincludeanevaluationofadeliveredimplementationplan.Stipend:ThecandidatewillbeexpectedtoapplyforcompetitivePhDscholarships(NHMRC,University,etc.)althougha3-yearPhDstipendisavailableforanexcellentcandidate.LocationTheresearchwillbeundertakenattheMurdochChildren'sResearchInstituteandMMiscoordinatedthroughtheAustralianGenomicsHealthAlliance.ThePhDcandidatewillenrolwiththeDepartmentofPaediatrics,UniversityofMelbourne.

InfectionandImmunity35.Doseoptimisationofantibioticsinchildrenwithcysticfibrosisusingpharmacokinetic-pharmacodynamicmodellingDrAmandaGweeamanda.gwee@rch.org.au0393455522Theaimofthisprojectistooptimiseantibioticdosinginchildrenwithcysticfibrosis.Theprojectinvolves:(I)leadingamulticentreprospectiveaudittocollectbloodsamplesinchildrenwithcysticfibrosis(ii)usingmodellingtodeterminethepharmacokinetics(whathappenstothedruginthebody)andpharmacodynamics(theeffectofthedruginthebody)ofantibioticsinchildrenwithCF.Themodelwillthenbeusedtosimulatetheantibioticdoserequiredtoimprovecareforchildrenwithcysticfibrosis.36.Applicationofintra-oral3-DimensionalScanningtomonitororalhealthinchildrenProfDaveBurgnerdavid.burgner@mcri.edu.au0399366730TheCOVID-19pandemichashighlightedtheurgentneedforimprovedoptionsfortele-health,includingtele-dentistry.Three-dimensionalscanningpromisesconsiderablepotentialforrecordingandmonitoringoralhealth.Althoughtraditionallyrestrictedclinicallytoorthodonticsandprosthodontics,recentrapiddevelopmentsin3Dtechnologieswillexpanditsapplicationtoamuchbroaderrangeofclinicalandresearchsettingsincludingremoteoralhealthassessmentandautomatizeddiagnostics.ThisPhDprojectwillevaluatethevalidityofanintra-oralscannertomeasurethepresenceandseverityofdentalcariesanddevelopmentaldefectsinchildrenofdifferentagesinbothprimaryandsecondarydentition.Theprojectwillbenestedwithinanumberoflargepopulation-basedandclinicalhigh-riskcohortsattheMelbourneChildren'sCampus.ThePhDinvolvesperformingclinicalassessments,includingdentalexaminationsand3Dintraoralscanning,onchildren,withasubstantialanalyticalcomponenttovalidatetheintraoralscannerforpopulationhealthresearchandasadiagnosticandpatientmanagementtool.Thesuccessfulapplicantwilljoinadynamic,supportiveandproductiveresearchteambasedinMelbourne,AustraliaandCopenhagen,Denmark.ThecandidatewillbebasedattheMCRIbutwillworkcloselywiththeproductdevelopmentteamat3Shape(Denmark).ThePhDprogramwillincludeafull-timePhDstipend,andpotentialfundingforinternationaltravel,includingpartofthecandidaturetobebasedinDenmark.Part-timecandidaturemaybeconsidered.37.ClusterRCTofamulti-componentinterventionpackagetoimprovematernalandchildhoodvaccinationinVictoriaA/ProfMargieDanchin

margie.danchin@rch.org.au0431144160Maternalandchildhoodvaccinationisvitaltoensurethehealthofwomenandchildren,butconcernregardingvaccinesafetyandeffectivenessremainsapressingissue.Uptakeofbothinfluenzaandpertussisvaccinesinpregnancyispoor,despitebeingstronglyrecommended.Thisleavesmanypregnantwomenandtheirinfantsneedlesslyvulnerable.Childhoodvaccinecoverageandtimeliness,includingbirthHepatitisBvaccine,arealsoanongoingchallenge.Pregnancyisacriticaltimeforvaccinedecision-making,whenexpectantparentsmustconsiderbothmaternalvaccinesandchildhoodvaccinesfortheirbaby.Todate,therehavebeennoevidenced-basedinterventionstooptimisematernalandchildhoodvaccineuptake.Toaddressthisimportantgap,wehavedevelopedaninnovative,evidence-based,multi-componentinterventionpackagetailoredformidwivesatthePractice,ProviderandParent(P3)levelstomeetthediverseandcomplexinformationneedsofpregnantwomen.OurpilotstudyfoundtheP3interventiontobeacceptableandfeasibleforusebymidwivesandparentsandinformedupdatinganddevelopmentofthenextiterationoftheP3-MumBubVaxintervention.Now,withamulti-disciplinaryteamofresearchersweneedtoassesstheimpactandcost-effectivenessofthisapproachtosupportrapidtranslationintopractice.WeareseekingaPhDstudenttoleadtheconductofaclusterrandomisedcontrolledtrialinVictoriatoevaluatetheP3-MumBubVaxinterventionpackageusingafactorialdesignforimprovinguptakeofinfluenzaandpertussisvaccinationamongpregnantwomen,timelyuptakeofroutineinfantvaccines,maternalvaccineknowledge,attitudesandbeliefsandmidwifeconfidenceindiscussingvaccination.Wewillalsoassesstheimplementationbarriersandfacilitatorstoinformadaptabilityandscalabilityandevaluatetheexpectedcost-effectivenessofP3-MumBubVaxcomparedtousualcare.ThetrialwillbeconductedinantenatalcentresinVictoriaalongsideGenerationVictoria(GenV),awhole-of-stateAustralianbirthcohortfordiscoveryandinterventionalresearch.

PopulationHealth38.GeneticsofchildhoodhearinglossDrValerieSungvalerie.sung@rch.org.au0393454363Congenitalhearinglossaffects1-3per1000children.Overthelastquartercentury,remarkableadvanceshavetransformedthesechildren'slifechances:universalnewbornhearingscreening,earlyaccesstotechnology,interventionandcochlearimplantation.Yet,earlydiagnosisandinterventiondonotguaranteeimprovedoutcomes.TheVictorianChildhoodHearingImpairmentLongitudinalDatabank(VicCHILD)isastatewidedatabank(withmorethan950hearing-impairedchildrentodate)designedtodiscoverthehiddenfactorsthatpredictlanguageandqualityoflifeoutcomes.Oneofthepossiblefactorsmaybetheunderlyinggeneticaetiology,poorlyunderstoodtodateduetothelackofcomprehensivediagnostictesting.Recentyearshaveseengreatadvancesingenetictesting.In2017-2018,exomesequencingwasofferedtonewbornsinVicCHILDwithmoderatetoprofoundhearingloss,leadingtomonogenicdiagnosesfor59of106

newborns,raisingdiagnosticratesfrom22%to56%oftheeligibleVicCHILDcohortandchangingmanagementfor51%.Translationofexomesequencingintoroutineclinicalcarenowdemandsevidenceastoitsprognosticpredictionoflong-termchildoutcomes,cost-utilityandcost-consequencebenefits.Weseekanoutstandingcliniciandoctoralresearchertocompleteexomesequencingfortherestofthe2017-2108VicCHILDcohortwithmildandunilateralhearingloss,andtocompletecollectionofthe5-7yearoldlongitudinaloutcomesofthewhole2yearVicCHILDcohort.39.AssociationsbetweenCOVID-19psychosocialstressorsandimmuneandcardiometabolicmarkersamongadolescentsA/ProfNaomiPriestnaomi.priest@anu.edu.auAdolescentsareathighriskofinfectionbytheSARS-CoV-2virus.Adolescentshavealsobeendisproportionatelyimpactedbythepandemicviaeducationaldisruption,isolation,employmentloss,financialandhousingstress,substantiallyincreasingtheriskofpopulationmentalillhealthanddeathbysuicide.COVID-19hasalsobeenaccompaniedby'asecondpandemic'ofracismthathasimpactedmanyadolescentsfromIndigenousandfromethnicminoritybackgrounds.Racism,includingmediaexposuretoracism,hasprofoundnegativeimpactsonadolescentmentalhealthincludingsuicidality,depression,anxiety,substanceuseaswellasphysiologicalchangessuchashighbloodpressureandraisedmarkersofinflammation.Associationsbetweenpsychosocialstressors,mentalhealthandimmuneandcardiometabolicmarkersarealsoincreasinglydocumentedamongadolescentsandyoungpeople.ExploringassociationsbetweenCOVID-19relatedpsychosocialstressorsandimmuneandcardiometabolicmarkersamongadolescentsisrequiredtoinformevidencebasedresponsestoaddresshealthinequitiesincardiometabolicdiseaseandmentalhealth.TheprojectwillusesecondarydatafromtheYoungLivescohortstudyof~1000adolescentstoinvestigatehowpsychosocialstressorsrelatedtotheCOVID-19pandemicareassociatedwithimmuneandcardiometabolicmarkersamongadolescents.Evidencegeneratedwillbeusedtoinformpolicydecisionmakingandactiontoreduceadolescenthealthinequitiesincardiometabolicdiseaseandmentalhealth.40.LongitudinalandseculartrendsinoutcomesforadolescentswithhearingimpairmentinVictoriaDrValerieSungvalerie.sung@rch.org.au0393454363helast25yearshaveseensignificantchangestomethodsofdetection,interventionandservicesavailabletochildrenborninVictoriawithahearingimpairment.Universalnewbornhearingscreening,earlyinterventionandcochlearimplantationhaverevolutionisedtheopportunitiesforhearing-impairedchildren,buttheirlanguageandlearningstilllagbehindtheirhearingpeers.SeverallongitudinalcohortstudiesinVictoriahavefollowedchildrenthroughchildhoodtoexaminelanguage,psychosocial,mentalhealthandqualityoflifeoutcomes.TheCHIVOSstudy(ChildrenwithHearingImpairmentinVictoriaOutcomeStudy)

followedchildrenbornin1991to1993(whendetectionwaslargelyopportunistic)withfollowupwavestakingplaceatages7to8,12to14and17to19.TheSCOUTstudy(StatewideComparisonofOutcomesStudy)followedchildrenbornadecadelaterbetweenMarch2003-February2005(whendetectionwasviariskfactorscreening)andthiscohorthavebeenfollowedupatages5to6,10to12andwillbeaged17to18atnextproposedfollowupin2021.TheVicCHILD(VictorianChildhoodHearingImpairmentLongitudinalDatabank)studybeganin2011/12,incorporatingtheSCOUTcohort(viainformedconsent)andinvitingallchildrenborninVictoriawithapermanenthearingimpairmentfrom2005onwardsintothestudy,withcontinuousfollowupsofchildrenaged5-7yearsand10-12yearsandproposedfuturefollowupatages17-18years.WeseekanoutstandingdoctoralresearchertoexaminelongitudinaloutcomesoftheSCOUTcohortandseculartrendsinoutcomesforadolescentsborninVictoriawithahearingimpairmentoverthelast25years.ThiswillinvolveassessmentoftheSCOUTcohortatage17-18yearsincludingparent-andchild-reportedoutcomes,directassessments,accessingacademic(NAPLAN)results,andbiologicalsampling.ExaminingseculartrendswillincorporatedataalreadycollectedfromtheCHIVOScohort.41.Inequitiesinchildren'smentalhealth:evidencetoinformprecisionpolicyresponsesProfSharonGoldfeldsharon.goldfeld@rch.org.auInequitiesinchildren'shealthanddevelopmentrefertodifferentialoutcomesthatareunjustandpreventable.Australianchildrenexposedtodisadvantagefrominfancyareathigherriskofpoormental,physicalandacademicoutcomesbylatechildhood.Theseinequitiestrackforwardintoadulthood,wheretheycarryhighcostsforindividualsandsociety.Reducingchildinequitiesisapublichealthpriority.WhileAustraliangovernmentsarecommittedtoreducinginequities,thetranslationofcurrentlyavailableevidenceintoeffectiveactioncontinuestobechallenging.TheChangingChildren'sChancesprojectworkscollaborativelywithpolicymakerstogenerateevidencethatidentifiesclearandactionablepolicypathwaystoreduceinequitiesinchildren'shealthanddevelopment.AChangingChildren'sChancesscholarshipisavailableforaPhDcandidatetocontributeamixed-methodsstudy.Theprojectwillinvestigatehowevidencerelatedtothemodifiablesocialdeterminantsofchildmentalanddevelopmentalhealthinequitiescaninformpolicydecisionmakingandaction.Theprojectwillinvolvequantitativeanalysisofexistingdata(e.g.theLongitudinalStudyofAustralianChildren)andinterviewswithstakeholders.Theoutcomeswillhelptoinformhowresearcherscanbetterdeliverevidencetomeaningfullyinformpolicy,andareexpectedtobeofhighrelevancetoeffortstoaddresstheimpactsofCOVID-19onchildren'smentalanddevelopmentalhealth.ThePhDwillbeconductedthroughtheUniversityofMelbourneandthesuccessfulcandidatewillbebasedattheMurdochChildren'sResearchInstitute.ThecandidatewillbesupportedbytheChangingChildren'sChancesteamandthebroaderresearchenvironmentoftheCentreforCommunityChildHealth.Keyreading:GoldfeldS,GrayS,AzpitarteF,etal.Drivingprecisionpolicyresponsestochildhealthanddevelopmentalinequities.HealthEquity.2019;3(1):489-494.

42.Theimpactofpositiveandadverseexperiencesonchildren'scardiovasculardiseaseriskandmentalhealthoutcomesA/ProfNaomiPriestnaomi.priest@anu.edu.auNon-communicablediseasesandmentalillnessaccountforasubstantialportionoftheglobalburdenofdisease.Thesediseasesoftenhavetheiroriginsinchildhood.AkeychallengefacinggovernmentsinternationallyisunderstandinghowtoeffectivelypreventNCDsandreduceinequitiesinhealthoutcomesattheearliestpossiblestage.Childrenaregrowingupinasocialenvironmentthatincludesbothadverseandpositiveexperiences.Exposuretochildhoodadversity(e.g.householdmentalillness)hasharmfuleffectsonphysicalandmentalhealththroughoutthelifecourse.Similarly,exposuretopositiveexperiences(e.g.astimulatinglearningenvironment)contributetooptimalhealthanddevelopmentaloutcomes.However,positivechildhoodexperiencesremainunder-exploredinrelationtolaterhealthoutcomes,includinghowtheybufferagainstadversity.Theprojectwillusequantitativeanalysisofexistingdata(e.g.theLongitudinalStudyofAustralianChildren)togenerateevidenceabouttheimpactofpositiveandadverseexperiencesonchildren'scardiovasculardiseaseriskandmentalhealthoutcomes.Findingscanbeusedtoinformpolicydecisionmakingandactiontoreduceinequitiesinchildren'sphysicalandmentalhealth.ThisPhDprojectisnotafundedproject,sothecandidatewillneedtoapplyforaPhDscholarshiporothertypesoffunding.ThePhDwillbeconductedthroughTheUniversityofMelbourneandthesuccessfulcandidatewillbebasedattheMurdochChildren'sResearchInstitute.ThecandidatewillalsobesupportedbytheChangingChildren'sChancesteamandthebroaderresearchenvironmentoftheCentreforCommunityChildHealth.TheChangingChildren'sChancesprojectworkscollaborativelywithpolicymakerstogenerateevidencethatcaninformhowexistingpolicyinterventionscanbeoptimisedtoreduceinequitiesinchildren'shealthanddevelopment.Keyreading:O'ConnorM,SlopenN,BecaresL,etal.Inequalitiesinthedistributionofchildhoodadversityfrombirthto11years.AcademicPediatrics.2020;20(5):609-618.43.ImprovinglifetimeoutcomesforbabiesinspecialcarenurseriesProfMelissaWakemelissa.wake@mcri.edu.auMorethan10%ofnewbornsareadmittedtospecialcarenurseries(SCN),manyexperiencinglifelongadverseoutcomes.Withinthe'GenerationVictoria'cohort,targetingall160,000Victorianbirthsovertwoyearsfrom2021andencompassingall28SCNs,thisPhDwillassistinsettingupanewstatewideSCNregistry.Itwillovercomeresearchchallengesofdispersedcareanddifficultiesinlong-termoutcomesmeasurementtobuildanevidencebaseforbetterphysical,mentalanddevelopmentaloutcomes.GenV'slinkeddatasets,digital'ePhenome'willsupportexplorationoftheimpactsofvariationsincareandcomparisonswiththegeneralpopulation.Itoffersimmenseopportunitiestoestablishacareerandleadershipintransformativenewbornandchildhealthservicesresearch.

44.PrecisionpredictionofmaternalandchildoutcomesfromroutinefetalultrasoundsProfMelissaWakemelissa.wake@mcri.edu.au Predictionofthegreatobstetricandnewbornsyndromesremainsfrustratinglyimpossible,resultinginavoidableburdentomaternalandchildhealthandhealthcareservices.Artificialintelligencecouldtransformthepredictivevalueofroutinefetalultrasounds-ifamega-repositoryexistedcombiningultrasoundswithwell-phenotypedoutcomes.ThisPhDwillhelpdevelopandcapitaliseonaninternationally-uniquestatewideconsentedrepositoryoffetalultrasoundsforVictorianbabiesborn2021-22andtheirmothers,workingwithinthe'GenerationVictoria'cohort,itslinkeddatasetsanddigital'ePhenome'.ThelandmarkGenVoffersimmenseopportunitiestoestablishacareerandleadershipinthedigitaltransformationofpregnancyand/orchildhoodhealth.