daf-12 Target Genes during C. elegans aging

daf-12 线虫衰老过程中的靶基因

• 批准号: 6815151
• 负责人: ALFRED L FISHER
• 金额: $ 11.64万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6815151
• 关键词: Caenorhabditis elegans; RNA interference; aging; alternatives to animals in research; biological models; biological signal transduction; chromatin immunoprecipitation; cytoprotection; environmental stressor; gene expression; genetic regulation; genetic regulatory element; geriatrics; heat; helminth genetics; hormone regulation /control mechanism; intermolecular interaction; longevity; microarray technology; nuclear receptors; oxidative stress; protein structure function; ultraviolet radiation

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in Geriatrics with a research focus on the basic Biology of Aging. The principal investigator has completed clinical training in Geriatrics and is now pursuing essentially full-time research using the free-living nematode, C. elegans, to study the genetic regulation of aging and lifespan determination. The training program consists of structured didactic work and mentored research experiences designed to build upon the principle investigator's prior research experience in the areas of DNA binding proteins, transcriptional regulation, and fruitfly, Drosophila, genetics. Specifically the program will develop new research abilities in the areas of Biology of Aging, C. elegans genetics, and Bioinformatics/Genomics. The proposal also includes a research program which seeks to advance the understanding of aging through study of the worm. Specifically, study will focus on the orphan nuclear hormone receptor daf-12. Target genes for this receptor are predicted to have important roles in regulating the aging of the worm. The timing of daf-12 in regulating lifespan will initially determined, and then target genes directly regulated by daf- 12 during this window of action will be isolated by using DNA microarrays with confirmation of direct regulation by chromatin immunoprecipitation. Isolated target genes will be characterized with respect to their roles in aging and responses to environmental stressors, such as heat, oxidative stress, bacterial pathogens, and UV radiation. The goal of these studies will be to identify new genes with roles in aging and develop the tools needed to ultimately understand the biochemical and molecular functions of these genes. The ultimate goal of the training program is to allow the principal investigator to develop a program in the basic Biology of Aging within a Geriatrics Division. An improved understanding of the biochemical events involved in aging and the responses of an organism to these events will greatly enhance our understanding of the aging process and the link between aging and disease. This understanding holds the potential for the development of treatments to address the negative consequences of aging or to prevent diseases associated with aging. Additionally, an improved understanding of the aging process will provide insight into the differences between geriatric patients and younger patients especially with regards to differences in disease symptoms and response to treatments.

描述（由申请人提供）：该提案描述了一项为期 5 年的培训计划，旨在发展老年病学的学术职业，重点研究衰老的基础生物学。首席研究员已完成老年病学临床培训，目前正在利用自由生活的线虫秀丽隐杆线虫进行全职研究，以研究衰老和寿命决定的基因调控。培训计划包括结构化的教学工作和指导研究经验，旨在建立在主要研究者之前在 DNA 结合蛋白、转录调控和果蝇、果蝇、遗传学领域的研究经验的基础上。具体来说，该项目将开发衰老生物学、线虫遗传学和生物信息学/基因组学领域的新研究能力。 该提案还包括一项研究计划，旨在通过对线虫的研究来增进对衰老的理解。具体来说，研究将集中在孤儿核激素受体 daf-12 上。预计该受体的靶基因在调节线虫衰老方面发挥重要作用。将初步确定daf-12调节寿命的时间，然后使用DNA微阵列分离在此作用窗口期间由daf-12直接调节的靶基因，并通过染色质免疫沉淀确认直接调节。分离的靶基因将根据其在衰老和对环境应激源（例如热、氧化应激、细菌病原体和紫外线辐射）的反应中的作用进行表征。这些研究的目标是识别在衰老中发挥作用的新基因，并开发最终了解这些基因的生化和分子功能所需的工具。 培训计划的最终目标是让主要研究者在老年病学部门制定衰老基础生物学计划。更好地了解与衰老相关的生化事件以及生物体对这些事件的反应将极大地增强我们对衰老过程以及衰老与疾病之间联系的理解。这种理解具有开发治疗方法的潜力，以解决衰老的负面后果或预防与衰老相关的疾病。此外，加深对衰老过程的了解将有助于深入了解老年患者和年轻患者之间的差异，特别是在疾病症状和治疗反应方面的差异。