Genetic Analysis of Drosophila Functional Aging

果蝇功能衰老的遗传分析

基本信息

批准号：
8825995
负责人：
ROLF BODMER
金额：
$ 117.03万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
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/8825995
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 cardiac pacing 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

项目摘要

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）：老化会导致多种系统和细胞类型的退化性变化。这些损失导致特定生理系统的功能下降，这些系统有助于渐进的发病率并最终导致死亡。基本老年病的两个基本问题来自这些中心观察。结构和功能内在生理下降的过程是什么，导致特定老年疾病的最终表达？功能衰老的不同表型在多大程度上由基本衰老过程的共同因素协调调节？该计划项目将通过有关遗传模型系统果蝇Melanogaster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，我们的计划具有四个总体目标。 1）在果蝇中建立多种功能衰老模型，与人类衰老表型具有很高的生理相关性，特别是在心脏，免疫和睡眠的衰老中。 2）评估胰岛素/IGF和TOR的寿命调节如何影响功能衰老的独立和砾岩轴。 3）发现通过遗传操作的方法（包括正向遗传筛查和候选因素的转基因分析），发现了年龄依赖性下降的致病机制。 4）评估功能衰老的显然分歧，同步方面是否由常见的衰老过程驱动。审查程序项目的各个组件核心A：行政核心，核心负责人Rolf Bodmer博士（CL）描述（由申请人提供）：核心A具有在该PPG不同项目之间提供领导，互动和协调的作用，以便促进他们实现其科学目标。核心A将监督项目负责人的两年一次会议的组织，通过科学顾问委员会（SAB）组织项目负责人的年度会议，并在整个PPG的总体目标上审查进度。由行政人员协助的该PPG的PI将确保科学议程和行政事务的无缝操作。核心A还将提供行政支持，其中包括对资金和研究分配的监控。 PI将至少每年至少两次针对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咨询委员会的报告，并将年度进度报告撰写和传输给NIA。 Core A的PI将咨询来自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。这些服务将寻求在项目的各种测定中的数据（例如，PCR，心脏起搏，肠道运动，睡眠回合频率等）中进行生物统计分析。此外，定性遗传学家塔塔尔（Tatar）博士塔塔尔（Tatar）和吉布森（Gibson）博士将提供生物统计学专家建议。核心A将监督该PPG的网页的启动和维护，这将允许在全球社区之间分发发现，同时实时启用共享协议，试剂以及信息的信息。