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（由申请人提供）：老化导致多种系统和细胞类型的退行性变化。这些损失引起特定生理系统的功能下降，导致进行性发病并最终死亡。从这些中心的观察中产生了基础老年学的两个基本问题。导致最终表现为特定老年疾病的内在生理结构和功能下降的过程是什么？不同的功能性衰老表型在多大程度上受潜在衰老过程的共同因素的协调调节？本计画将针对这些问题，以果蝇为遗传模式系统，进行功能性老化的整合研究。为了实现这一目标，我们的计划有四个总体目标。1)建立多种与人类衰老表型具有高度生理相关性的果蝇功能性衰老模型，特别是在心脏、免疫和睡眠衰老方面。2)评估胰岛素/IGF和TOR对寿命的调节如何影响功能性衰老的独立和综合轴。3)通过遗传操作方法，包括正向遗传筛选和候选因子的转基因分析，发现心脏、免疫和睡眠年龄依赖性下降的致病机制。4)评估功能性衰老的明显不同的异步方面是否是由一个共同的衰老过程驱动的。 审查可持续发展项目的各个组成部分 核心A：行政核心，Rolf Bodmer博士，核心负责人（CL） 描述（由申请人提供）：核心A的作用是在本PPG的不同项目之间提供领导、互动和协调，以促进它们实现其科学目标。核心A将监督项目负责人半年一次会议的组织工作，组织项目负责人与科学咨询委员会的年度会议，并审查整个项目编制小组总体目标的进展情况。该PPG的PI在行政人员的协助下将确保科学议程和行政事项的无缝运行。核心A还将提供行政支助，包括监测资金和研究拨款。主要参与者将至少每年两次审查项目和核心的支出和资源分配情况。行政核心还将负责整理科学咨询委员会的报告，以及编写和向国家科学院提交年度进展报告。Core A的PI将咨询附近的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。将寻求这些服务，以便在对项目的各种测定（例如，PCR、心脏起搏、肠道动力、睡眠发作频率等）的数据进行生物统计分析时提供咨询。此外，核心B领导人Tatar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将监督项目规划小组网页的启动和维护，该网页将允许在全球社区中传播调查结果，同时使各项目能够真实的分享方案、试剂以及信息。