THE BRAIN INITIATIVE® Brain Research through Advancing Innovative Neurotechnologies ® (BRAIN) Initiative Joshua Gordon, MD, PhD Walter Koroshetz, MD BRAIN Multi-Council Working Group Co-Chairs
THEBRAININITIATIVE®
BrainResearchthroughAdvancingInnovativeNeurotechnologies® (BRAIN)
InitiativeJoshuaGordon,MD,PhDWalterKoroshetz,MD
BRAINMulti-CouncilWorkingGroupCo-Chairs
THEBRAININITIATIVE®
Goal:Elucidatecircuit structureandfunctiontounderstand:• Howthebrainmoves,plans,executes• Howtomonitor/manipulatecircuitsforimprovedfunction
• That disorderedbraincircuitscauseneuro/mental/substanceabusedisorders
Long-termgoal:Makecircuitabnormalitiesthebasisofdiagnostics, andnormalizationofcircuitfunction thetargetofintervention
Molecular/StructuralPathology
CircuitDysfunction
Neuro/Mental/SubstanceAbuseFunctionalDisability
FosterInnovation:FocusonBrainCircuits
Emphasizetechnologydevelopment
FIRSTFIVEYEARS
Emphasizediscovery
drivenscience
SECONDFIVEYEARS
THEBRAININITIATIVE®
1.Discoveringdiversity:Identifyandprovideexperimentalaccesstothedifferentbraincelltypestodeterminetheirrolesinhealthanddisease.
2.Mapsatmultiplescales:Generatecircuitdiagramsthatvaryinresolutionfromsynapsestothewholebrain.
3.Thebraininaction:Produceadynamicpictureofthefunctioningbrainbydevelopingandapplyingimprovedmethodsforlarge-scalemonitoringofneuralactivity.
4.Demonstratingcausality:Linkbrainactivitytobehaviorwithpreciseinterventionaltoolsthatchangeneuralcircuitdynamics.
SevenHighPriorityResearchAreasBrainCellTypes
ToolsforCircuit
Diagrams
Tech.toMonitorNeuralActivity
PreciseInter-
ventionalTools
THEBRAININITIATIVE®
5.Identifyingfundamentalprinciples:Produceconceptualfoundationsforunderstandingthebiologicalbasisofmentalprocessesthroughdevelopmentofnewtheoreticalanddataanalysistools.
6.Advancinghumanneuroscience:Developinnovativetechnologiestounderstandthehumanbrainandtreatitsdisorders;createandsupportintegratedhumanbrainresearchnetworks.
7.FromBRAINInitiativetothebrain:Integratenewtechnologicalandconceptualapproachesproducedingoals#1-6todiscoverhowdynamicpatternsofneuralactivityaretransformedintocognition,emotion,perception,andactioninhealthanddisease.
TheoryandDataAnalysisTools
AdvanceHumanNeuro-science
IntegrateApproaches
SevenHighPriorityResearchAreas
THEBRAININITIATIVE®
Training/Dissemination?Theory
*AllFY17informationisanestimate,aswedonotknowtheFY17budget.President’sbudget~$195M
ScientificStewardship:NIHBRAINInvestment
ScientificgoalsandoverarchingprinciplesoftheBRAIN2025reportandtheBRAINMulti-CouncilWorkingGroup(MCWG)continuetoguideNIHfundingdecisionsBRAINMCWGassessedprogressinFeb.2017,recognizedinvestmentstowards65/74short-termgoals
0
20
40
60
80
100
120
140
160
180
200
Millions
Training/Dissemination
HumanImaging/Modulation
UnderstandingCircuits
NeuralRecording/Modulation
Cell/CircuitTools
CellTypes
Theory/Training/Dissemination
*
THEBRAININITIATIVE®
• Blueprint• NCCIH• NEI• NIA• NIAAA• NIBIB• NICHD• NIDA• NIDCD• NIMH• NINDS• OBSSR• OD• ORWH
FiscalYear
ActualBudget
#New BRAINAwards
21st CenturyCures
ACDWGRecommendation
FY14 $46.1M 58
FY15 $85M 67 $100M
FY16 $154M 108 $190M
FY17 TBD $10M $300M
FY18 TBD $86M $400M
FY19 TBD $115M $500M
NIHBRAINInvestment
THEBRAININITIATIVE®BRAIN21st CenturyCures
InnovationFunds
$0
$50
$100
$150
$200
$250
$300
$350
$400
$450
$500
FY17 FY18 FY19 FY20 FY21 FY22 FY23 FY24 FY25 FY26
DollarsinMillions
21st CenturyCuresActauthorizes$1.511billiontobetransferredfromtheBeauBidenCancerMoonshot&NIHInnovationAccountforBRAINresearchthrough2026
Fundsneedtobeappropriatedeachyear,nottoexceed theseamounts:• FY17:$10,000,000• FY18:$86,000,000• FY19:$115,000,000• FY20:$140,000,000• FY21:$100,000,000• FY22:$152,000,000• FY23:$450,000,000• FY24:$172,000,000• FY25:$91,000,000• FY26:$195,000,000
THEBRAININITIATIVE®InnovationFund Budget
ScenarioFYYear
OriginalCuresFund Competing Noncompeting MultiYear
Funded Total
2017 10,000,000 10,000,000 - 10,000,000
2018 86,000,000 38,000,000 10,000,000 38,000,000 86,000,000
2019 115,000,000 33,500,000 48,000,000 33,500,000 115,000,000
2020 140,000,000 _________ 81,500,000 58,500,000 140,000,000
2021 100,000,000 28,500,000 71,500,000 100,000,000
2022 152,000,000** 45,000,000 62,000,000 45,000,000 152,000,000
2023 450,000,000** 45,000,000 73,500,000 331,500,000 450,000,000
2024 172,000,000** 118,000,000 54,000,000 172,000,000
2025 91,000,000 89,500,000 1,500,000 91,000,000
2026 195,000,000 89,500,000 105,500,000 195,000,000
Total 1,511,000,000 200,000,000 598,500,000 712,500,000 1,511,000,000
**Potentialtimeframetotakeadvantageofemergingscientificopportunitiesand/ortousefundstoadvancedisseminationofnewtools/technologiesordevelopnewdatasharingplatforms.
THEBRAININITIATIVE®
SCAPE:Novel3Dmicroscopymethodforhigh-speed,volumetricimagingoflivingtissuevisualizesspontaneousneuronalfiringinwhole-brainofawake,behavingmiceandDrosophilalarvae
Diamondelectrodescanmeasurestimulation-drivenmonoaminetransmitterreleaseinbasalgangliaofhumanswithgreaterlongevityandstrength
Two-PhotonHolographicStimulationofred-shiftedopsin,ReaChR:Red-shiftedopsins reacttolongerwavelengthsoflight,mayreachdeepbrainstructures
Bouchardetal.,NaturePhotonics, 2015
Bennet etal.,FrontiersinHumanNeuroscience, 2016
Chaigneau etal.,FrontiersinCellularNeuroscience, 2016
BRAIN-supportedTechnologyLeapstoCatalyzeNeuroscience
THEBRAININITIATIVE®
MaintainflexibilitytoallowustotakeadvantageofemergingscientificopportunitiesUtilizeavarietyoffundingapproachestoensuresustainedfundingBalanceregularandmulti-yearfundingofgrants• Abilitytospreadfundsovermorethanoneyeartoprovideamoresteadystreamofresources
• Leverageadministrativeandcompetitivesupplements• Ensurefullfundingofallgrantsby2026
21st CenturyCuresInnovationFunds:StrategiesforBRAIN
THEBRAININITIATIVE®
$150
$150
$150
$100
$75$386
$500
BrainCellTypes
ToolsforCircuit
Diagrams
Tech.toMonitorNeuralActivity
PreciseInter-
ventionalTools
TheoryandDataAnalysisTools
AdvanceHumanNeuro-science
IntegrateApproaches&Principles
HighlevelestimateofpotentialdistributionofInnovationFundsoverthenext9yearsFY2022,2023,2024largefundingincreasesmaybeopportunitytotakeadvantageofscientificopportunitytorapidlyadvanceanareaand/ordevoteadditionalfundstooneoftheBRAINinitiativepriorities,particularlycostlygoalse.g.:• Humanstudies• Disseminationofnew
technologies/training• Infrastructurefordatascienceandnew
datasharingplatforms
21st CenturyCuresInnovationFunds:PotentialDistribution
Dollarsinmillions
THEBRAININITIATIVE®
Mission:TocoordinateandfacilitatecommunicationsfromitsmembersrelatedtotheBRAINInitiative
Websiteprovidesplatformforfundingopportunities,news,achievements,resources,andmoregatheredfromacrossthefederalandnon-federalparticipantsoftheBRAINInitiative
www.braininitative.org
AdvancingResearchthroughPartnerships:BRAINInitiativeAlliance
THEBRAININITIATIVE®RecruitingOutstandingWorkforce:
EngagingManyDisciplinesDepartmentCategory(forContactandMultiPIs) FY15 ~FY16Biochemistry 11 12Biology/cellbiology/Microbiology/Pathology/Immunology 43 36Chemistry 17 11Genetics 4 3Biostatistics/math/computerscience 12 33Physics 16 14Engineering(allcategories) 119 141Neuroscience/Neurology 146 141Neurosurgery 14 47Psychiatry/Psychology 17 69Radiology/Radiation-Diagnostic 31 61Bioimaging/Imaging 15 8
THEBRAININITIATIVE®
0%
10%
20%
30%
40%
Applications Scored ScoreBetterthan40 Awarded
NewInvestigator(NI):EligibleContactApplicants
FY14-16R01 FY14 FY15 FY16
RecruitingOutstandingWorkforce:New,EarlyStageInvestigators
ControlisneuroscienceacrossallICs.
0%
5%
10%
15%
20%
Applications Scored ScoreBetterthan40 Awarded
EarlyStageInvestigator(ESI):EligibleContactApplicants
FY14-16R01 FY14 FY15 FY16
• TheBRAINInitiativeisreachingearlystageinvestigatorsandtheirapplicationsaredoingspectacularlywell
• NewBRAINFOAsattractbothNIandESIapplicants.SourceoftheincreaseinFY15andFY16
• TheR21FundingopportunityforlargescalerecordingcontinuestoattractNIandESIapplicants
THEBRAININITIATIVE®
Novelmethodforclassifyingcelltypesusinghighthroughputgeneticsequencingallowedcomprehensiveclassificationofretinalbipolarneurons
Genomeeditingofsynthetictargetarraysforlineagetracing(GESTALT)trackscellfateinwholecomplex,multicellularorganisms
Thezebrafish optomotor response:Integrationofwhole-brainimaging,behavioralanalysis,functionalperturbations,andnetworkmodelingtobuildabrain-scalecircuitmodelofanorientingbehavior
3Dmapofmotorcortextractpathwaysinmicerevealasystematicallyorganizedconnectome ofmotoroutputprojections
BRAIN-supportedTechnologyLeapstoCatalyzeNeuroscience
Shekhar etal.,Cell, 2016
McKennaetal.,Science, 2016
Naumann etal.,Cell 2016
Jeong etal., ScientificReports 2016
THEBRAININITIATIVE®
Dr.ArnoldKriegstein andcolleaguesidentifycandidateentryreceptorforZika virusinneuralstemcells
SinglecellRNA-seq analysisofdifferentcelltypesduringearlydevelopment(CellStemCell)• Examinedexpressionofseveral
candidateentryreceptorsforZika virus
• CandidateAXLishighlyexpressedinseveralcelltypes,includinghumanradialglialcells• Lossofradialgliafounderpopulationsleadstomicrocephaly
• AXLexpressionpatternisconservedinmice,ferrets,andhumaniPSCs – modelsforinfectivityanddevelopmentaleffectsofZika virus
ScientificAdvancements:CellTypes