Dissecting complex regulation by C. elegans DAF-16
Dissecting complex regulation by C. elegans DAF-16
批准号:
7896672
负责人:
HEIDI A TISSENBAUM
金额:
$41.0万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-08-01 至 2012-07-31
关键词:
1-Phosphatidylinositol 3-KinaseAffectAgeAge of OnsetAgingAging-Related ProcessBiochemicalBioinformaticsBiologicalBiological ModelsBiological ProcessBoxingCaenorhabditis elegansCellsComplexCoupledCouplingDataDefectDevelopmentDiabetes MellitusDiapauseFamilyFamily memberFatty acid glycerol estersGene TargetingGenesGenetic TranscriptionGenome StabilityGenomicsGoalsGonadal structureHealthIGF-1 Signaling PathwayIndividualInsulinInsulin-Like Growth Factor IInsulin-Like-Growth Factor I ReceptorLeadLesionLocationLongevityMammalsMetabolismMethodsMolecularMolecular GeneticsNatureNematodaObesityOrganismOrthologous GeneOutputPathway interactionsPhenotypePhysiological ProcessesPopulationProcessProteinsProtocols documentationRegulationResistanceResistance developmentRoleSignal TransductionSignaling Pathway GeneSpecificityStressSystemTechnologyTestingTo specifyaging populationcell typechromatin immunoprecipitationcombatdosageforkhead proteingenome wide association studygenome-wideinsightmutantneuronal cell bodyprogramsprotein functionreceptor
中文摘要
在接下来的几年里,美国人口中老年人的数量将急剧增加。与此相关的人口老龄化,将是大量激增的病例与年龄有关的疾病。
英文摘要
Over the next several years, the number of older individuals in the U.S. population will increase dramatically. Associated with this aging population, will be a large surge in the number of cases of age-associated illnesses.
Understanding the aging process at the molecular level will undoubtedly give important clues to combat these illnesses. We seek to increase the health of individuals by delaying the onset of age-associated illnesses. Studies on aging over the past decade from many labs have revealed the importance of the
forkhead transcription family (FOXO). Here, we use the nematode, C. elegans as our model system because it has a single well-conserved FOXO family member, DAF-16. Altering levels of this protein lead to changes in life span, fat storage, dauer diapause and stress resistance. We seek to define how daf-16 coordinates its multiple input and output signals to specify multiple developmental programs such as life span, fat storage, stress resistance, and development. To accomplish this goal, we will use cutting edge technologies to first identify DAF-16 interacting proteins and determine how they influence target choice. Second, we will define DAF-16 direct targets using genome wide approaches. These studies will which push towards a biochemical and genomic understanding of the aging process. In addition, we define how one protein can regulate multiple processes. The high degree of conservation between worms and mammals in this pathway indicate that these studies will also undoubtedly have implications for our understanding of the mammalian aging process.
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