Genetic Analysis of Drosophila Functional Aging

果蝇功能衰老的遗传分析

• 批准号: 8079787
• 负责人: ROLF BODMER
• 金额: $ 128.11万
• 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/8079787
• 关键词: Genetic; Analysis; Drosophila; Functional; Aging

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）：衰老会导致多种系统和细胞类型的退行性变化。这些损失会导致特定生理系统的功能衰退，从而导致发病率进行性上升并最终导致死亡。这些中心观察结果引发了基础老年学的两个基本问题。结构和功能的内在生理衰退的过程是什么，最终导致特定的老年疾病的表现？功能性衰老的不同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果蝇功能老化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具有高度生理相关性的果蝇功能衰老的多种模型，特别是心脏、免疫和睡眠的衰老。 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轴和综合轴。 3) 通过基因操作方法，包括正向遗传筛选和候选因素转基因分析，发现年龄依赖性心脏、免疫和睡眠衰退的致病机制。 4) 评估功能性衰老的明显不同、异步方面是否是由共同的衰老过程驱动的。 计划项目各个组成部分的审查 核心 A：行政核心，Rolf Bodmer 博士，核心领导者 (CL) 描述（由申请人提供）：核心 A 的职责是在该 PPG 的不同项目之间提供领导、互动和协调，以促进他们实现其科学目标。核心 A 将监督项目负责人每两年一次的会议的组织，组织项目负责人与科学顾问委员会 (SAB) 的年度会议，并审查整个 PPG 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务的无缝运作。核心 A 还将提供行政支持，包括资金和研究分配的监控。项目负责人将每年至少审查两次项目和核心的支出和资源分配。行政核心还将负责整理科学顾问委员会的报告，以及撰写并向 NIA 传送年度进展报告。 Core A的PI会咨询附近加州大学圣地亚哥分校数学系的统计学家，提供统计服务。这些服务将用于对来自项目的各种检测的数据进行生物统计分析（例如，PCR、心脏起搏、肠道蠕动、睡眠频率等等）。此外，Core B领导者Tatar博士和定性遗传学家Gibson博士将提供生物统计学方面的专家建议。核心 A 将监督该 PPG 网页的启动和维护，该网页将允许在全球社区中分发研究结果，同时能够在项目之间实时共享协议、试剂和信息。