Happyholidaystooneandall!Thisshortsciencevideobringstomindallthosetwinklinglightsnowbrighteningthenight,aswemarkthebeginningofwinterandshortestdayoftheyear.Thisvideoalsohelpstoremindusaboutthepowerofconnectionthisholidayseason.
Itshowsamotorneuroninamouse’sprimarymotorcortex.Inthisportionofthebrain,whichcontrolsvoluntarymovement,heavilybranchedneuralprojectionsinterconnect,sendingandreceivingsignalstoandfromdistantpartsofthebody.Asinglemotorneuroncanreceivethousandsofinputsatatimefromotherbranchingsensorycells,depictedinthevideoasanarrayofblinkinglights.It’sonlythroughtheseconnections—throughopencommunicationandcooperation—thatvoluntarymovementsarepossibletonavigateandenjoyourworldinallitswonder.Oneneuron,likeoneperson,can’tdoitallalone.
ThosedatacamefromTheMachineIntelligencefromCorticalNetworks(MICrONS)program,supportedbytheIntelligenceAdvancedResearchProjectsActivity(IARPA).It’spartoftheOfficeoftheDirectorofNationalIntelligence,oneofNIH’sgovernmentalcollaboratorsintheBRAINInitiative.
TheMICrONSprogramaimstobetterunderstandthebrain’sinternalwiring.Withthisincreasedknowledge,researcherswilldevelopmoresophisticatedmachinelearningalgorithmsforartificialintelligenceapplications,whichwillinturnadvancefundamentalbasicsciencediscoveriesandthepracticeoflife-savingmedicine.Forinstance,theseapplicationsmayhelpinthefuturetodetectandevaluateabroadrangeofneuralconditions,includingthosethataffecttheprimarymotorcortex.
Prettycoolstuff.So,asyouspendthisholidayseasonwithfriendsandfamily,letthisvideoanditstwinklinglightsremindyouthatthere’smuchmoretotheseasonthaneating,drinking,andwatchingfootballgames.
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Globalhealthresearchalsoencompassesdatascience,economics,genetics,climatechangescience,andmanyotherdisciplines.Formorethan50years,FogartyhasbeenbuildingpartnershipsamonginstitutionsintheU.S.andabroad,whiletrainingthenextgenerationofscientistsfocusedonuniversalhealthneeds.
America’sinvestmentinFogartyhaspaidrichdividends
Duringthepandemic,inparticular,we’veseenresearcherstrainedbyourprogramsmakescientificdiscoveriesthatcontributedtointernationalsecurity.TakeJessicaManning,aformerFogartyfellowwhonowconductsmalariaresearchinPhnomPenh,Cambodia.HerteamattheMinistryofHealthsequencedtheviralstrainofSARS-CoV-2,thecauseofCOVID-19,infectingthefirstCambodianpatientanddocumentedearlythespreadofthisnovelcoronavirusoutsideofChina.
Similarly,ChristianHappi,directoroftheAfricanCentreofExcellencefortheGenomicsofInfectiousDisease,Ede,Nigeria,sequencedthefirstSARS-CoV-2genomeinAfrica.Happiwasabletodoitbyadaptingthesequencingandanalyticalpipelinesthathe’dcreatedbackwhenhewasaFogartygranteestudyingEbola.
InBotswana,SikhulileMoyoleveragedtheskillshe’dacquiredwhilesupportedbyaFogartyHIVresearchtraininggrantwithMaxEssex,HarvardSchoolofPublicHealth,Cambridge,MA,totrackCOVID-19mutationsforhiscountry’sMinistryofHealth.LastNovember,healertedtheworldofanewOmicronvariant.Withinsixweeks,Omicronbecamethedominantglobalstrain,challengingtheabilityofCOVIDvaccinestocontrolitsspread.IntheDominicanRepublic,WilliamDuke,anationalcommissionmember,usedwhathe’dlearnedasaFogartytraineetohelpcreateanationalCOVID-19interventionplantopreventandcontrolthedisease.
Fogarty’sfosteringofglobalhealthleadersisonewayweadvancescientificexpertisewhileensuringournation’sbiosecurity.Anotherisbyfindingeffectivewaystostudyabroadthesamehealthconditionsthataffectourownpopulation.
Researchersinotherfieldsalsodiscoveruniqueopportunitiestoinvestigatepopulationswithhighratesofdisease.SianaNkya,aFogartygranteebasedinTanzania,hasdevotedhercareertostudyingthegeneticdeterminantsofsicklecelldisease,whichaffectsmanypeoplearoundtheworld,includingintheU.S.WehopethatUS-Africanpartnershipsmightdevelopimproved,affordabletreatmentsandacureforallpatientswiththisdevastatingdisease.Similarly,peopleintheU.S.haveaccesstostate-of-the-artHIVtreatmentstudiesinplacesaroundtheglobewhereincidenceratesarehigher.
FogartyhassupportedmanymilestoneachievementsinHIVresearchovertheyears.Amongthemisastudythattookplaceinninecountries.Theresearch,ledbyMyronCohenoftheUniversityofNorthCarolinaatChapelHill,establishedthatantiretroviraltherapycanpreventsexualtransmissionofHIV-1amongcouplesinwhichonepersonisinfectedandtheotherisnot.Infact,thisresearchinformscurrentHIVtreatmentrecommendationsworldwide,includingintheU.S.
OtherexamplesofGlobalBrainprograminvestigationswithbroadimplicationsinourowncountryincludestudyingearlypsychosisinChina;capacitybuildingforschizophreniaresearchinMacedonia;exploringfamilyconsequencesfromtheZikavirusinBrazil;andstudyingdementiaandrelatedhealthandsocialchallengesinLebanon.
ThesearejustafewexamplesofFogarty’sworkanditsuniquemission.WhatismostremarkableaboutFogartyisthatjustunder90percentofourgrantsareco-fundedbyatleastoneotherNIHinstitute,center,oroffice.Collaboration,bothwithinbordersandacrossthem,isFogarty’sformulaforsuccess.
Note:Dr.LawrenceTabak,whoperformsthedutiesoftheNIHDirector,hasaskedtheheadsofNIH’sInstitutesandCenters(ICs)tocontributeoccasionalguestpoststotheblogtohighlightsomeoftheinterestingsciencethattheysupportandconduct.Thisisthe22ndintheseriesofNIHICguestpoststhatwillrununtilanewpermanentNIHdirectorisinplace.
Fluseasonisnowuponus,andprotectingyourselfandlovedonesisstillaseasyasheadingtothenearestpharmacyforyourannualflushot.Thesevaccinesareformulatedeachyeartoprotectagainstuptofourcirculatingstrainsofinfluenzavirus,andtheygenerallydoagoodjobofthis.Whattheycan’tdoispreventfutureoutbreaksofmorenovelfluvirusesthatoccasionallyspilloverfromotherspeciesintohumans,therebyavoidingafutureinfluenzapandemic.
Onthislatterandmore-challengingfront,there’ssomeencouragingnewsthatwaspublishedrecentlyinthejournalScience[1].AnNIH-fundedteamhasdevelopedaunique“universalfluvaccine”that,withoneseasonalshot,thathasthepotentialtobuildimmuneprotectionagainstanyofthe20knownsubtypesofinfluenzavirusandprotectagainstfutureoutbreaks.
Whilethisexperimentalfluvaccinehasn’tyetbeentestedinpeople,theconcepthasshowngreatpromiseinadvancedpre-clinicalstudies.Humanclinicaltrialswillhopefullystartinthecomingyear.Theresearchersdon’texpectthatthisuniversalfluvaccinewillpreventinfluenzainfectionaltogether.But,likeCOVID-19vaccines,thenewfluvaccineshouldhelptoreducesevereinfluenzaillnessesanddeathswhenapersondoesgetsick.
Whilethisisn’tthefirstattempttodevelopauniversalfluvaccine,pastattemptshadprimarilyfocusedonalimitednumberofconservedantigens.Anantigenisaproteinorothersubstancethatproducesanimmuneresponse.Conservedantigensarethosethattendtostaythesameovertime.
Becauseconservedantigenswilllooksimilarinmanydifferentinfluenzaviruses,thehopewasthatvaccinestargetingasmallnumberofthemwouldaffordsomebroadinfluenzaprotection.Butthefocusonastrategyinvolvingfewantigenswasdrivenlargelybypracticallimitations.Usingtraditionalmethodstoproducevaccinesbygrowingfluvirusesineggsandisolatingproteins,itsimplyisn’tfeasibletoincludemorethanaboutfourtargets.
That’swhererecentadvancesinmRNAtechnologycomein.WhatmakesmRNAsoniftyforvaccinesisthatallyouneedtoknowistheletters,orsequence,thatencodesthegeneticmaterialofavirus,includingthesequencesthatgettranslatedintoproteins.
AresearchteamledbyScottHensley,PerelmanSchoolofMedicineattheUniversityofPennsylvania,Philadelphia,recognizedthattheeaseofdesigningandmanufacturingmRNAvaccinesopenedthedoortoanalternateapproachtodevelopingauniversalfluvaccine.Ratherthanlimitingthemselvestoafewantigens,theresearcherscouldmakeanall-in-oneinfluenzavaccine,encodingantigensfromeveryknowninfluenzavirussubtype.
Morestudyisneeded,ofcourse,butearlyindicationsareencouraging.Thevaccinegeneratedstrongandbroadantibodyresponsesinanimals.Importantly,itworkedbothinanimalswithnopreviousimmunitytothefluandinthosepreviouslyinfectedwithfluviruses.Thatcameasgoodnewsbecausepastinfectionsandresultingantibodiessometimescaninterferewiththedevelopmentofnewantibodiesagainstrelatedviralsubtypes.
Inmoregoodnews,theresearchersfoundthatvaccinatedmiceandferretswereprotectedagainstsevereillnesswhenlaterchallengedwithfluviruses.Thosevirusesincludedsomethatwerecloselymatchedtoantigensinthevaccine,alongwithsomethatweren’t.
Thefindingsofferproof-of-principlethatmRNAvaccinescontainingawiderangeofantigenscanofferbroadprotectionagainstinfluenzaandlikelyothervirusesaswell,includingthecoronavirusstrainsresponsibleforCOVID-19.Theresearchersreportthatthey’removingtowardclinicaltrialsinpeople,withthegoalofbeginninganearlyphase1trialinthecomingyear.Thehopeisthatthesedevelopments—driveninpartbytechnologicaladvancesandlessonslearnedoverthecourseoftheCOVID-19pandemic—willhelptomitigateorperhapsevenpreventfuturepandemics.
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