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Effec%veSpecificAims
RobertJ.Milner,PhD•JoanM.Lakoski,PhD
ResearchandScholarshipareacyclethatdefine
yourresearchiden%ty
October30,2015
Toaccomplisharesearchprojectsuccessfully
youneedresources...
Research
Your
Research
Iden%ty
Space
Scholarship
Exper%se/Personnel
Time
Equipment
Money
Materials/Subjects
Yourequesttheseresourceswitharesearchproposal
Therearekeyelements
towri%ngasuccessfulproposal
Itisessen%altostartwithagoodques%on
WhatisthemechanismofX?
Yourproposalmusthaveahighlikelihoodof
producingresultsthatwillhaveanimpact:
—EmphasizeSignificance,Innova;on!
IsthisdrugabeOertreatment?
Yourproposalmustbeeasytounderstand:
—Keepitsimple,concise&logical!
DoesthischangeinclinicalpracPce
improveoutcomes?
Youmustknowwhatisrequiredfortheproposal:
—ReadtheInstruc;ons!
ForNIHresearchproposals
highimpactisdeterminedby...
Youmustknowhowtheproposalwillbereviewed:
—WritetotheReviewCriteria!
thelikelihoodfortheprojecttoexerta
sustained,powerfulinfluence
ontheresearchfield
Thebestresearchques%onshave
significanceandimpact
Youmustproposetoanswertheresearchques%on
withatestablehypothesis
Doestheprojectaddressanimportantproblem?
Agapinknowledgeortreatment?
Ifthegoalsoftheprojectareachieved,
•  howwillscienPficknowledge
orclinicalpracPcebeimproved?
•  willtheresultsexertasustained,powerful
influenceontheresearchfield
“Nowyouknowthat,
whatdoyouknow?”
Funded
Goodresearchishypothesisdriven
Ahypothesisisageneralstatement,
oXendescribingbiologicalmechanisms
butnotdirectlyrelatedtoexperiment.
HypothesesallowyoutomakespecificpredicPons
thatcanbetestedexperimentally.
Hypothesis
Predic%on
FloydBloom,MD
©2015RobertJ.Milner,Ph.D.&JoanM.Lakoski,Ph.D.
1
Ahypothesisisnotthesameasapredic4on:
—don’tconfusethem!
Predic4onsdefinetheoutcomesofyourproposal
—“Nowyouknowthat,whatdoyouknow?”
Hypothesis: ThefirststepinviralinfecOonisbinding
oftheviralenvelopeproteinXYZtothe
cellsurfacereceptorABC.
Theseexperimentswill...
1.  definethemechanismofvirusbinding
tothecellsurface
2.  provideanopportunityforfuture
developmentofanO-viraltherapies
Predic;on: TreaOngcellswithanObodiesagainstABC
willinhibitthebindingbetweenXYZand
ABCanddecreaseviralinfecOon.
Youmuststatetheoutcomesofyourproposal
—donotassumethatthereviewerwill
ThehypothesisisNOT:
AnObodiestoABCareaneffecOveanOviraltherapy.
Connec4ngthedots:
thelogicalframeworkofaresearchproposal
Research
Ques;on
Testable
Hypothesis
Aboveall,remember...
theproposalmusttell
acoherentstory
A successful proposal
is an effective act of
communication
Experimental
Predic;ons
theoutcomesmustadvance
theresearchques;on
Defined
Outcomes
Yourgoalistoexciteandpersuadeyourreviewer
Howdoyouwantthereviewer
toreacttoyourproposal?
??
Writesimply,clearly,andlogically
ApplyGeorgeOrwell’s
rulesforwri;ngwell...
!!!
Neverusealongwordwhereashortonewilldo.
Ifitispossibletocutawordout,alwayscutitout.
Neverusethepassivewhereyoucanusetheac4ve.
Breakanyoftheserulessoonerthansayanything
outrightbarbarous.
ZZZZZZZ
Poli@csandtheEnglishLanguage,Orwell,1945(hNp://www.erudite.io/orwell/poliOcs)
Image:GeorgeOrwell’spresscard:hNp://www.netcharles.com/orwell/
©2015RobertJ.Milner,Ph.D.&JoanM.Lakoski,Ph.D.
2
Neverusealongwordwhereashortonewilldo
UseshortAnglo-Saxonwordsrather
thanlongLaOn-derivedwords:
endnotterminate
startnotcommence
Ifitispossibletocutawordout,alwayscutitout
Mostadjec4vesandadverbsareunnecessary
—cutthemout!
✓ ✗
Deletethe“wiggle”words:
—anumberof(some,several)
—inorderto(to)
—isableto(can)
Avoidjargon
—yourreadersmaynotbeexpertsinyourfield
Removeexcessmodifiers:
—quite,totally,completely,absolutely
Avoidnominaliza4ons(nounsderivedfromverbs)
—usethecorrespondingverbs:
introducenotintroducOon
providenotprovision
Neverusethepassivewhereyoucanusetheac4ve
Avoidredundancies:
—(knowledgeable)experts
—(new)innovaOon
Whatorwhoismorepersuasive?
Ac;ve:
Johnkickedtheball.
4words;17leLers
Passive:
TheballwaskickedbyJohn. 6words;22leLers
Donotbeafraidtouse“I”or“We”
say—“Wewilltreatthecellswith...”
not—“Thecellswillbetreatedwith...”
Beawarethatthereismuchconfusionaboutthe
passivevoice:whatitisandwhentouseit.
ScreeningforProstateCancer:
U.S.PrevenOveServices
TaskForceRecommendaOon
Yourgoalshouldbetowriteclearly,concisely,directly.
RudyGiuliani
“Thereportdoesnot
makesense.”
—>thepowerofnarra;ve...
http://commons.wikimedia.org/wiki/File:Rudy_Giuliani.jpg
Tellagoodstory...
TheSpecificAimspageisthemostimportantpart
ofyourproposal...
Theaudiencewillbeconvincedbyyourevidence
butexcitedbyyournarra;ve...
NarraOveshavethreeparts:
1.  Set-Up(exposiOon)
—theproblemorques@on
Describesconciselythegoals,
objecOves&outcomesofthe
proposedstudies
Problem
2.  Conflict/Ac4on
—howyouwillsolvethatproblem
Ac4on
Isausefulsummaryfor
obtainingearlyfeedbackon
yourproposal(realitycheck!)
3.  Resolu4on
—theoutcomeyouexpect
Result
Isthehardestpartofthe
proposaltowrite
TheSpecificAimspagewilldefineyournarra;ve
Youmustdevote;metodraY&polishtheSpecificAims!
©2015RobertJ.Milner,Ph.D.&JoanM.Lakoski,Ph.D.
3
Theinstruc4onsforthethesisproposalstate
thattheSpecificAimspageshould...
AgoodformatforaSpecificAimsPageisasandwich
Firstparagraph
Describethehypothesis(es)youaretesOng.
topic,goals,objecOves,
hypothesis,raOonale
WhatareyourresearchobjecOves?
Set-Up
SpecificAims
Whatconclusionscouldbemadefromyourfindings?
objecOves,descripOon
Beconcise,clearandlogical.Provideanapproximate
Ometableforaccomplishingtheseaims.Youraims
arethetestofyourhypothesis.
Lastparagraph
impact,outcomes
Ac4on
Resolu4on
Whatareyouplanningtodo?
Whatisyourhypothesis?
Youmustgrabthereviewer’sa[en4onatthestart
—consideropeninglinesinfic;on...
Comparewith...
“Itwasadarkandstormynight;therainfellintorrents,
exceptatoccasionalintervals,whenitwascheckedby
aviolentgustofwindwhichsweptupthestreets(forit
isinLondonthatourscenelies),raNlingalongthe
house-tops,andfiercelyagitaOngthescantyflameof
thelampsthatstruggledagainstthedarkness.”
“Allhappyfamiliesarealike;eachunhappyfamilyis
unhappyinitsownway.”
LeoTolstoyAnnaKarenina(1878)
“ItwasabrightcolddayinApril,andtheclockswere
strikingthirteen.”
GeorgeOrwellNineteenEighty-Four(1949)
EdwardGeorgeBulwer-LyNon,PaulClifford(1830)
“WeweresomewherearoundBarstowontheedgeof
thedesertwhenthedrugsbegantotakehold.”
HunterThompsonFearandLoathinginLasVegas(1972)
UsingtheTemplateforaSpecificAimsPage...
TheTemplateliststhe
essenOalelementsofa
SpecificAimspage
— completeeach
elementasasentence
—combinethesentences
intoanarraOve
—polish
—review
—polishagain
—askforfeedback
—polishagain
Thefirstparagraphprovidesthera4onaleforthe
proposedstudies
©2015RobertJ.Milner,Ph.D.&JoanM.Lakoski,Ph.D.
WhatistheTopic?
WhatistheGapinknowledge?
Whatisthelong-termGoalofyourresearch?
WhatarethespecificObjec4vesfortheproposal?
WhatistheHypothesis?
WhatistheEvidenceforthehypothesis?
WhatistheRa4onale/Significance?
Youhaveahalfpageorless(~300words)tosetthe
stagefortheproposal&excitethereviewer!
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StarttheSpecificAimswithaconcise,ac4ve
statementintroducingthetopicoftheproposal
Nextdescribethegapinknowledgeorunmetneed
thatyourproposalwilladdress
InfanOleRespiratoryVirus(IRV)isanewagentthat
causesarapidinflammaOonofthelungsandposes
anincreasinghealthrisktoyoungchildren.
AlthoughIRVresemblesotheradenoviruses,the
exactmechanismofitspathogenesisisunknown,
providingliNleguidancefortreatment.
PancreaOccanceristhefourthmostcommoncauseof
deathfromcancerintheUSA;only5%ofpaOents
survivelongerthanfiveyears.
ThemajorityofpaOentsarenotdiagnosedunOlthe
cancerisinthelaterstagesandtherearecurrently
nobiomarkersforearlydetecOonofthedisease.
DiabetesisamajorhealthconcernintheUnited
States.
ButtheincidenceofdiabetesconOnuestoriseand
theonsetofdiseaseoccursatayoungerage.
Yourturn:
Describethegapinknowledgeorunmetneed
thatyourproposaladdresses.
Yourturn:
Composeatopicsentenceforyourproposal.
Describethelong-termgoalofyourresearch
Describethespecificobjec4vesofyourproject
Thelongtermgoalofourlaboratoryistodevelop
effecOvetherapiesagainstinfecOousagentsthrough
understandingtheirbasicbiology.
ThisproposalwillfocusonunderstandingIRV
infecOonthroughdefiningthemechanismofvirus
bindingtoitshostcells.
OurlaboratoryfocusesonthefuncOonofmicro-RNAs
(miRNAs)inthedetecOonandtreatmentofcancers.
IwillfocusthisproposalontheexpressionofmiRNAs
inpancreaOccancerwiththegoalofdeveloping
biomarkersforearlydetecOon.
Ourlong-termgoalistounderstandhowbehavioral
modificaOoncanpreventtheearlyonsetofdiabetes.
ThisproposalwillfocusontesOngbehavioral
intervenOonsinadolescents.
Yourturn:
Describethelongtermgoalofyourproject.
Definethehypothesisunderlyingyourproposal
Yourturn:
Describethespecificobjec4vesofyourproject.
Describetheevidenceforthehypothesis
Byhomologywithotherrespiratoryadenoviruses,we
hypothesizethatIRViniOatesinfecOonbybindingof
theIRV-knobproteintotheCARprotein.
InpreliminarystudiesusinganinvitrosystemIRVis
abletoinfectCARposiOvehostcellsbutnotCARnegaOvecells.
Ourhypothesisisthattumorigenesisresultsin
dysregulaOonofbothcellularandsecretedmiRNAs.
InpreliminarystudiesIhaveshownthatmiRNA-179A
andmiRNA-208Dareincreasedinexpressionin
pancreaOctumorcellscomparedtonormalOssue.
On-lineapproaches,parOcularlyinvolvingmobile
media,arewell-acceptedbyadolescents.Therefore,
ourhypothesisisthattheseapproacheswillbemost
effecOveinthispopulaOon.
On-linebehavioralintervenOons(“mHealth”)have
beenusedsuccessfullyinadultdiabeOcpopulaOons;
preliminarystudiesdemonstratethatthisapproach
canbesuccessfullytranslatedtoadolescents.
Yourturn:
Definethehypothesisforyourproject.
©2015RobertJ.Milner,Ph.D.&JoanM.Lakoski,Ph.D.
Yourturn:
Definetheevidenceforyourhypothesis.
5
Describethera4onalefortheproposal
YourSpecificAimsshouldfitthescopeofyoureffort
ThisproposalwillenablemetoapplytheexperOseof
mylaboratorywithadenovirusestounderstandthe
pathogenesisofanovelvirus.
Fittheaimstotheeffort:
foraKAward:oneperson(you!)over3–5years
Thisproposalwillapplyourextensiveexperiencewith
miRNAstoanimportantandcommoncancer.
AvoidconOngentaims(the“fatalflaw”)
Typicallynomorethanthreeaims
Providea@melineforyouraimsintheproposal
Thisproposalisacomprehensiveassessmentofthe
effecOvenessofmHealthapproachesinadolescents.
Aim Year 1
Year 2
Year 3
1
2
Yourturn:
Definethera4onaleforyourproject.
Firstdefinethescopeofyouraims
3
Firstdefinethescopeofyouraims
1.  Todeterminetheaminoacidsequenceofthe
IRVknobprotein.
1.  Tocharacterizetheexpressionof
miRNA-179AandmiRNA-208DinpancreaOc
tumorcells.
2.  TocharacterizetheregionsoftheIRV-knob
proteinnecessaryforbindingtothehostcell
CARprotein.
2.  TodeterminetherelaOonshipbetween
expressionofmiRNA-179AandmiRNA-208D
andpancreaOctumorigenesis.
3.  TodevelopmonoclonalanObodiesagainst
regionsoftheIRV-knobproteinthatinhibit
bindingtoCAR.
Firstdefinethescopeofyouraims
3.  TomeasuretheexpressionofcirculaOng
miRNA-179AandmiRNA-208DinpaOents
withpancreaOccancer.
Expandeachspecificaimtoprovideashort
descrip4ve4tle&briefdescrip4on
1.  TodevelopamobilemHealthapplicaOon
designedtopromotehealthybehaviorsin
adolescents.
2.  Toassesstheacceptabilityandbehavior
changesinadolescentsatriskofdeveloping
early-onsettypeIIdiabetes.
Aim2.TodeterminetheregionsoftheIRV-knobprotein
necessaryforbindingtothehostCARprotein.
OurhypothesispredictsthatalteraOonoftheenvregion
oftheknobproteinwilldecreasebindingtothehost
cellCARprotein.WewilltestthispredicOonby
a)  GeneraOngvariantsoftheknobproteinwith
structuralalteraOonsinenv.
b)  AssessingbindingtotheCARproteininvitro.
Yourturn:
Writea4tle&descrip4onforaspecificaim.
©2015RobertJ.Milner,Ph.D.&JoanM.Lakoski,Ph.D.
6
Thelastparagraphfocusesoninnova4on,impact
andoutcomes
Thelastparagraphfocusesoninnova4on,impact
andoutcomes
Innova4on:
IRVisarecentlydiscoveredvirus:thesestudiesarethe
firstaNempttocharacterizethemechanismofits
infecOon.
Outcomes&Impact:
TheproposedstudieswilldefinethemechanismofIRV
infecOonandprovideafoundaOonforimmune
therapy.
Thisproposalappliesanovelapproach—miRNAsas
biomarkers—tothediagnosisofpancreaOccancer.
DevelopmentofbiomarkersforearlydetecOonhasthe
potenOalfordramaOcimprovementinthesurvival
rateforpancreaOccancer.
Toourknowledge,thisproposalisthefirstaNemptto
usemHealthapproachesforbehavioralintervenOon
inadolescents.
Thesestudieswillprovideanew,cost-effecOve
approachtocontrollingtheearlyonsetofdiabetes.
Yourturn:
Describethenovelaspectsofyourproject.
Considerincludingadiagramtoillustrateyour
specificaims
Specific
Aim#1
Yourturn:
Describetheoutcomes&impactofyourproject.
Nextsteps...
Puttheelementsintoacoherent&logicalnarra;ve,
polish,andgetfeedback.
Checkpoint*—checkthefollowing:
q  MySpecificAimscantestmyhypothesis.
q  TheyaredoablewithinthegrantperiodIam
requesOng.
q  Theaimsareconcreteandwell-focused.
q  Icandefineendpointsmypeerreviewerswillbe
abletoassess.
Specific
Aim#2
Specific
Aim#3
*NIAIDGrantsTutorials:
hNp://www.niaid.nih.gov/researchfunding/grant/pages/aag.aspx
Wellwri[enspecificaimshelpyou...
Youcanalsouseyourspecificaimsto...
Sortoutthelogicofyourproposal:
—howmanyaims
—dependenceofaimsoneachother
—feasibilityandscope
IdenOfyyourresearchprioriOes
—andwhatyoumaysOllneedtolearn
Takeownershipofyourresearchideas
—animportantstepinbuildingyouridenOty
asanindependentinvesOgator.
©2015RobertJ.Milner,Ph.D.&JoanM.Lakoski,Ph.D.
TalkwithaProgramOfficer
Testyourthinkingbygewngfeedbackonyour
ideasinasafeandconstrucOvemanner
OpennewopportuniOesasyoudevelopyourideas
andlookforpotenOalresearchcollaborators.
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