Genetic Analysis of Drosophila Functional Aging

果蝇功能衰老的遗传分析

• 批准号: 8248172
• 负责人: ROLF BODMER
• 金额: $ 121.28万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8248172
• 关键词: Address; Administrative Personnel; Affect; Age; Aging; Aging-Related Process; Biological Assay; Biological Models; Biometry; California; Cardiac; Cardiovascular system; Cessation of life; Communities; Complex; Consult; Consultations; Cutaneous; Data Analyses; Development; Disease; Drosophila genus; Drosophila melanogaster; Elderly; Endocrine; Epilepsy; Expenditure; Frequencies; Funding; Future; Gene Expression Regulation; Genetic; Genetic Models; Genetic Screening; Gerontology; Goals; Growth; Human; Huntington Disease; Immune; Individual; Insulin; Lead; Leadership; Longevity; Lung; Maintenance; Mathematics; Methods; Modeling; Monitor; Morbidity - disease rate; Pathology; Peripheral; Phenotype; Physiological; Principal Investigator; Process; Progress Reports; Protocols documentation; Reagent; Regulation; Reporting; Research; Resource Allocation; Rodent; Role; Services; Signal Transduction; Sleep; Structure; System; Time; Transduction Gene; Transgenic Organisms; Universities; Variant; Work; Writing; age related; base; body system; cancer type; cell motility; cell type; fly; functional decline; genetic analysis; genetic manipulation; human disease; meetings; mortality; mutant; neuropathology; operation; programs; reproductive; senescence; statistical service; tool; web page

DESCRIPTION (provided by applicant): Aging leads to degenerative change in multiple systems and cell types. These losses induce the functional decline of specific physiological systems that contribute to progressive morbidity and ultimately to death. Two fundamental questions for basic gerontology arise from these central observations. What are the processes of intrinsic physiological decline in structure and function that lead to the eventual expression of specific geriatric disorders? To what extent are different phenotypes of functional aging coordinately regulated by common factors of an underlying aging process? This program project will address these questions with integrated research on functional aging of a genetic model system, Drosophila melanogaster. To achieve this goal, our program has four overall aims. 1) Establish multiple models of functional aging in Drosophila melanogaster with high physiological relevance to human senescent phenotypes, specifically in the senescence of cardiac, immune and sleep. 2) Assess how insulin/IGF and TOR regulation of lifespan affects independent and conglomerate axes of functional aging. 3) Discover pathogenic mechanisms underlying age dependent decline in cardiac, immune and sleep by methods of genetic manipulation including forward genetic screens and transgenic analysis of candidate factors. 4) Assess whether apparently divergent, asynchronous aspects of functional senescence are driven by a common process of aging. REVIEW OF INDIVIDUAL COMPONENTS OF THE PROGRAM PROJECT CORE A: ADMINISTRATIVE CORE, Dr. Rolf Bodmer, Core Leader (CL) DESCRIPTION (provided by applicant): Core A has the role to provide the leadership, interaction and coordination between the different projects of this PPG in order to facilitate them in meeting their scientific goals. Core A will oversee the organization of bi-annual meetings of the project leaders, organize annual meetings of the project leaders with the Scientific Advisory Board (SAB) and to review progress on the overall goals of the PPG as a whole. The PI of this PPG assisted by administrative personnel will assure seamless operation of the scientific agenda and administrative matters. Core A will also provide the administrative support, which includes the monitoring of funds and research allocations. The PI will review expenditures and resource allocations for the projects and cores, at least twice a year. The administrative core will also be responsible for collating the reports from the scientific advisory boards, as well as writing and transmitting the annual progress report to NIA. The PI of Core A will consult with a statistician from the nearby Department of Mathematics at the University of California at San Diego to provide statistical services. These services will be sought for consultation in biostatistical analysis of data from the various assays of the projects (for example, PCR, cardiac pacing, gut motility, sleep bout frequency, and many more). In addition, Core B leader Dr. Tatar and Dr. Gibson, a qualitative geneticist, will provide expert advice in biostatistics. Core A will oversee the launch and maintenance of a Web page for this PPG, which will allow distribution of findings among the global community, while enabling sharing protocols, reagents as well as information among the projects in real time.

描述(申请人提供)：老化导致多种系统和细胞类型的退行性变化。这些丢失导致特定生理系统的功能衰退，从而导致进行性发病并最终导致死亡。这些中心观察引出了基础老年学的两个基本问题。结构和功能的内在生理性衰退的过程是什么，最终导致特定的老年疾病的表现？不同的功能衰老表型在多大程度上受到潜在衰老过程的共同因素的协调调节？该计划项目将通过对遗传模型系统--黑腹果蝇的功能衰老的综合研究来解决这些问题。为了实现这一目标，我们的计划有四个总体目标。1)建立与人类衰老表型高度相关的多种果蝇功能衰老模型，特别是心脏衰老、免疫衰老和睡眠衰老。2)评估胰岛素/胰岛素样生长因子和TOR对寿命的调节如何影响功能衰老的独立轴和集合轴。3)通过基因操作的方法，包括正向遗传筛选和候选因素的转基因分析，发现心脏、免疫和睡眠随年龄下降的致病机制。4)评估功能衰老的明显不同、不同步的方面是否由共同的衰老过程驱动。 对计划项目的各个组成部分进行评审 核心A：行政核心，罗尔夫·博德默博士，核心领导(CL) 描述(由申请人提供)：核心A的作用是领导、互动和协调本PPG的不同项目，以促进它们实现其科学目标。核心A将监督项目领导人两年一次的会议的安排，与科学咨询委员会(SAB)一起组织项目领导人的年度会议，并审查整个项目小组总体目标的进展情况。在行政人员的协助下，PPG的PI将确保科学议程和行政事项的无缝运作。核心A还将提供行政支助，包括监测资金和研究拨款。PI将审查项目和核心的支出和资源分配，每年至少审查两次。行政核心还将负责整理科学咨询委员会的报告，并编写年度进展报告并将其转交国家臭氧机构。核心A的PI将咨询附近加州大学圣地亚哥分校数学系的统计学家，以提供统计服务。这些服务将在项目的各种分析(例如，聚合酶链式反应、心脏起搏、肠道动力、睡眠频率等)的生物统计分析中寻求咨询。此外，Core B负责人鞑靼博士和定性遗传学家吉布森博士将提供生物统计学方面的专家建议。核心A将监督这一项目小组网页的启动和维护工作，该网页将允许在全球社区中分发调查结果，同时使各项目能够实时分享协议、试剂以及信息。