Programmed Cell Death in Drosophila Development

果蝇发育中的程序性细胞死亡

基本信息

批准号：
7912582
负责人：
Kimberly A McCall
金额：
$ 26.94万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-09 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7912582
关键词：
Affect Animals Apoptosis Apoptotic Autophagocytosis Biological Models Cardiovascular Diseases Caspase Cell Death Cell Death Process Cells Cellular Stress Cellular biology Cessation of life Classification Collection Complex Data Development Disease Drosophila genus Family member Genes Genetic Genetic Screening Goals Human Insulin Insulin Signaling Pathway Malignant Neoplasms Mammals Mitochondria Modeling Molecular Morphology Nature Necrosis Neurodegenerative Disorders Nurses Oogenesis Ovarian Ovary Pathway interactions Phenotype Play Relative (related person)Research Role Signal Pathway Signaling Pathway Gene Stress System Systems Analysis Testing Transmission Electron Microscopy egg fly gene function insight insulin signaling lipid metabolism mitochondrial autophagy mutant new therapeutic target novel nutrition public health relevance research study response

项目摘要

DESCRIPTION (provided by applicant): Programmed cell death plays a central role in development and in many diseases. The long term goal of our research is to understand the mechanisms of programmed cell death in the Drosophila ovary, a model system with unique advantages in genetics and cell biology. The cell death genes identified thus far in Drosophila are generally homologous to the genes controlling cell death in mammals. The vast majority of cells that undergo cell death in Drosophila use a common pathway that is increasingly well-understood. However, cell death in the ovary occurs by distinct genetic pathways. This proposal aims to uncover the mechanisms controlling two types of cell death that occur in the fly ovary: developmental cell death of nurse cells, and stress-induced death of entire follicles. Stress-induced cell death requires caspases, whereas caspases are only partially required for developmental nurse cell death. Recent findings indicate that autophagy and mitochondrial morphological changes are occurring during both forms of cell death. The proposal aims to uncover the contribution of autophagy and mitochondria to cell death in the ovary. Additionally a genetic screen will be carried out to identify genes that function in ovarian cell death, perhaps in a pathway that acts in parallel to the caspases. Nutrition and the insulin signaling pathway are known to control egg chamber progression through oogenesis. Components of the insulin signaling pathway will be investigated for their effects on both autophagy and apoptosis in the ovary. Given the high conservation of cell death mechanisms between Drosophila and mammals identified thus far, we expect that pathways that we uncover in the fly ovary will be conserved in humans. A complete understanding of the diverse mechanisms controlling cell death may reveal new therapeutic targets for diseases with excessive or insufficient cell death such as neurodegenerative disorders and cancer. Public Health Relevance: Programmed cell death plays a central role in development and in many diseases. The long term goal of our research is to understand the mechanisms of programmed cell death in the Drosophila ovary, a model system with unique advantages in genetics and cell biology. A complete understanding of the diverse mechanisms controlling cell death may reveal new therapeutic targets for diseases with excessive or insufficient cell death such as neurodegenerative disorders and cancer.

描述（由申请人提供）：程序性细胞死亡在发育和许多疾病中发挥着核心作用。我们研究的长期目标是了解果蝇卵巢中程序性细胞死亡的机制，这是一个在遗传学和细胞生物学方面具有独特优势的模型系统。迄今为止在果蝇中鉴定的细胞死亡基因通常与哺乳动物中控制细胞死亡的基因同源。果蝇中绝大多数经历细胞死亡的细胞都使用一种日益被人们所了解的共同途径。然而，卵巢中的细胞死亡是通过不同的遗传途径发生的。该提案旨在揭示控制果蝇卵巢中发生的两种细胞死亡的机制：护理细胞的发育性细胞死亡和压力诱导的整个卵泡死亡。应激诱导的细胞死亡需要半胱天冬酶，而发育性护士细胞死亡仅部分需要半胱天冬酶。最近的研究结果表明，在两种形式的细胞死亡过程中都会发生自噬和线粒体形态变化。该提案旨在揭示自噬和线粒体对卵巢细胞死亡的贡献。此外，还将进行基因筛选，以确定在卵巢细胞死亡中起作用的基因，可能是在与半胱天冬酶平行作用的途径中。众所周知，营养和胰岛素信号通路通过卵子发生来控制卵室进展。将研究胰岛素信号通路的组成部分对卵巢自噬和细胞凋亡的影响。鉴于迄今为止发现的果蝇和哺乳动物之间细胞死亡机制的高度保守性，我们预计我们在果蝇卵巢中发现的途径在人类中也将得到保守。对控制细胞死亡的多种机制的全面了解可能会揭示细胞死亡过度或不足的疾病（例如神经退行性疾病和癌症）的新治疗靶点。公共健康相关性：程序性细胞死亡在发育和许多疾病中发挥着核心作用。我们研究的长期目标是了解果蝇卵巢中程序性细胞死亡的机制，这是一个在遗传学和细胞生物学方面具有独特优势的模型系统。对控制细胞死亡的多种机制的全面了解可能会揭示细胞死亡过度或不足的疾病（例如神经退行性疾病和癌症）的新治疗靶点。