grant
Investigating the molecular mechanisms underlying sleep disruption in Smith-Kingsmore Syndrome
Organization UNIVERSITY OF CALIFORNIA AT DAVISLocation DAVIS, UNITED STATESPosted 1 Apr 2026Deadline 30 Nov 2029
NIHUS FederalResearch GrantFY2026AKTAcuteAddressAffectAkt proteinAllelesAllelomorphsAnabolismAnimal ModelAnimal Models and Related StudiesAnimalsAssayAutophagocytosisAutoregulationBehaviorBehavioralBioassayBiochemicalBiological AssayBody TemperatureBody Temperature RegulationBody ThermoregulationBody TissuesBrainBrain Nervous SystemCRISPRCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas systemCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCancersCare GiversCaregiversCas nuclease technologyCell BodyCell Communication and SignalingCell Culture TechniquesCell FunctionCell PhysiologyCell ProcessCell SignalingCell modelCellsCellular FunctionCellular PhysiologyCellular ProcessCellular modelChronicCircadian DysregulationCircadian RhythmsClinicalClock proteinClustered Regularly Interspaced Short Palindromic RepeatsClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyComplementComplement ProteinsComplexConfocal MicroscopyCyclicityDNA mutationDegenerative Neurologic DisordersDevelopmental DelayDevelopmental Delay DisordersDisease ProgressionDrosophilaDrosophila genusDrosophila melanogasterDysfunctionEncephalonExhibitsFK506 Binding Protein 12-Rapamycin Associated Protein 1FKBP12 Rapamycin Complex Associated Protein 1FRAP1FRAP1 geneFRAP2FeedbackFliesFoundationsFunctional disorderFutureGene TranscriptionGenesGenetic ChangeGenetic DiseasesGenetic TranscriptionGenetic defectGenetic mutationGenotypeGerm LinesGerm-Line MutationGliaGlial CellsGoalsHereditary MutationHeterozygoteHomeostasisHourHumanHuman Cell LineHuman GeneticsHyperactivityHyperphagiaImmunoblottingIntellectual disabilityIntellectual functioning disabilityIntellectual limitationIntermediary MetabolismIntracellular Communication and SignalingInvertebrataInvertebratesKnock-inKnowledgeKolliker's reticulumLocomotor ActivityMalignant NeoplasmsMalignant TumorMammaliaMammalsMeasuresMechanistic Target of RapamycinMegalencephalyMetabolic ProcessesMetabolismMitochondriaModelingModern ManMolecularMotor ActivityMutationNerve CellsNerve Impulse TransmissionNerve TransmissionNerve UnitNervous SystemNervous System Degenerative DiseasesNervous System DiseasesNervous System DisorderNervous System PhysiologyNeural CellNeural Degenerative DiseasesNeural degenerative DisordersNeurocyteNeurodegenerative DiseasesNeurodegenerative DisordersNeurodevelopmental DisorderNeurogliaNeuroglial CellsNeurologic Body SystemNeurologic Degenerative ConditionsNeurologic DisordersNeurologic ManifestationsNeurologic Organ SystemNeurologic Signs and SymptomsNeurologic SymptomsNeurologic functionNeurological Development DisorderNeurological DisordersNeurological ManifestationsNeurological Signs and SymptomsNeurological functionNeuronal TransmissionNeuronsNon-neuronal cellNonneuronal cellNyctohemeral RhythmOutcomeOvereatingParentsPatient CarePatient Care DeliveryPatient outcomePatient-Centered OutcomesPatient-Focused OutcomesPatientsPeriodicityPhenotypePhosphorylationPhysiologicPhysiologic ThermoregulationPhysiologicalPhysiological HomeostasisPhysiologyPhysiopathologyProtein Kinase BProtein PhosphorylationProteinsProto-Oncogene Proteins c-aktQOLQuality of lifeRAC-PK proteinRAFT1RNA ExpressionRegulationReportingResearchRhythmicityRoleSeizuresSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSleepSleep DeprivationSleep Wake CycleSleep disturbancesSmith-Kingsmore syndromeSpecific Child Development DisordersSubcellular ProcessSymptomsTestingTherapeuticThermoregulationTissuesTranscriptionTransgenic OrganismsTranslationsTwenty-Four Hour RhythmVariantVariationWestern BlottingWestern ImmunoblottingWorkaberrant sleepautophagyaxon signalingaxon-glial signalingaxonal signalingbiological signal transductionbiosynthesisc-akt proteincare for patientscare of patientscaring for patientscell culturecell culturescircadiancircadian abnormalitycircadian clockcircadian disruptioncircadian disturbancecircadian dysfunctioncircadian impairmentcircadian pacemakercircadian processcircadian rhythmicitycomplementationdaily biorhythmdeficient sleepdegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdisrupted sleepdisturbed sleepflyfruit flygain of function mutationgenetic conditiongenetic disordergenome mutationgerm-line defectgermline variantglia signalingglial signalingheterozygosityimpaired sleepin vivoinadequate sleepinsufficient sleepintellectual and developmental disabilityirregular sleepknockinlimited intellectual functioningmTORmalignancymammalian target of rapamycinmitochondrialmodel of animalmolecular clockmutantneoplasm/cancernerve cementnerve signalingnervous system functionneural manifestationneural signalingneurodegenerative illnessneurodevelopmental diseaseneurological diseaseneuronalneuronal signalingneurotransmissionparentpathophysiologypatient oriented outcomespolyphagiapoor health outcomeprotein blottingproto-oncogene protein RACproto-oncogene protein aktrac protein kinasereduced health outcomerelated to A and C-proteinsleep behaviorsleep debtsleep deficiencysleep deficitsleep difficultysleep disruptionsleep dysregulationsleep habitsleep insufficiencysleep losssleep to wake transitionsleep to wakefulness transitionsleep wakefulness cyclesleep/wake behaviorsleep/wake disruptionsleep/wake disturbancesleep/wake transitionssocial roletransgenictranslationunclassified variantvariant of uncertain clinical significancevariant of uncertain significancevariant of undetermined significancevariant of unknown significanceworse health outcome
Description preview
Project Summary/Abstract
Smith-Kingsmore Syndrome (SKS) is a recently discovered human genetic disorder caused by gain-of-function
mutations in the mechanistic target of rapamycin (mTOR) gene. SKS patients exhibit variable symptoms,
including sleep disruptions, intellectual disability, developmental delay, megalencephaly, seizures, and…
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