Dissecting complex regulation by C. elegans DAF-16

解析秀丽隐杆线虫 DAF-16 的复杂调控

• 批准号: 7655731
• 负责人: HEIDI A TISSENBAUM
• 金额: $ 41万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7655731
• 关键词: 1-Phosphatidylinositol 3-Kinase; Affect; Age; Age of Onset; Aging; Aging-Related Process; Biochemical; Biological; Biological Models; Biological Process; Caenorhabditis elegans; Colorado; Complex; Coupled; Coupling; Data; Development; Diabetes Mellitus; Diapause; Family; Family member; Fatty acid glycerol esters; Fellowship; Gene Targeting; Genes; Genetic Transcription; Genomics; Goals; Growth; Health; Human Resources; Individual; Insulin; Insulin-Like Growth Factor I; Insulin-Like-Growth Factor I Receptor; Laboratories; Lead; Location; Longevity; Mammals; Metabolism; Methods; Molecular; Molecular Genetics; Nematoda; Obesity; Organism; Orthologous Gene; Output; Pathway interactions; Phosphorylation; Population; Postdoctoral Fellow; Process; Proteins; Protocols documentation; Regulation; Resistance; Resistance development; Role; Signal Pathway; Signal Transduction; Specificity; Stress; System; Technology; Testing; To specify; Work; aging population; chromatin immunoprecipitation; combat; dosage; forkhead protein; genome wide association study; genome-wide; insight; programs; protein function; receptor; research study

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.

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。