Mechanisms of cell corpse clearance

细胞尸体清除机制

基本信息

批准号：
8434200
负责人：
Kimberly A McCall
金额：
$ 30.01万
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：
2011
资助国家：
美国
起止时间：
2011-07-05 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8434200
关键词：
Animal Model Animals Antibodies Bioinformatics Candidate Disease Gene Caspase Cell Death Cell Death Signaling Process Cell Separation Cells Complement DNA Microarray Chip Data Defect Development Drosophila genus Epithelial Epithelial Cells Excision Gene Proteins Genes Genetic Genetic Screening Goals Homeostasis Human Human body Immune System Diseases Immune response In Situ Hybridization Inflammation Label Lead MAPK14 gene MAPK8 gene Molecular Molecular Profiling Nerve Degeneration Neuroglia Nurses Ovary Pathway interactions Phagocytes Phagosomes Process Proteomics RNA Interference Reporter Research Project Grants Role Signal Transduction Signaling Molecule Starvation Surveys System Tissues Transgenic Organisms cell type egg fly gene function human disease insight macrophage molecular marker mutant network models prevent research study

项目摘要

DESCRIPTION (provided by applicant): The efficient removal of dead cells is an important process in animal development and homeostasis. Cell corpses are often engulfed by professional phagocytes such as macrophages. However, some tissues have limited accessibility to circulating cells, and engulfment is carried out by neighboring non-professional phagocytes such as epithelial cells. The mechanisms of cell corpse recognition, engulfment and phagosome breakdown are only partially understood. The Drosophila ovary provides an excellent system for the study of engulfment by non-professional phagocytes. The ovary is closed to circulating cells, and degeneration of entire egg chambers can be induced easily by starvation. In such degenerating egg chambers, the germline nurse cells are engulfed by the surrounding somatic follicle cells. This engulfment process happens synchronously and rapidly at the onset of cell death, however the genetic requirements for follicle cell engulfment are completely unknown. This proposal aims to identify the genes and pathways required for engulfment by follicle cells. First, known engulfment genes and candidate signaling molecules will be investigated for their role in engulfment by follicle cells. Second, engulfing follicle cells will be isolated and their expression profiles will be compared to non-engulfing follicle cells using DNA microarray and proteomic approaches. Third, genetic screens will be conducted to identify new engulfment genes. Genes identified through these approaches will be characterized for their roles in engulfment in follicle cells and other tissues. These findings are expected to reveal the signaling mechanisms that are required for an epithelial cell to switch to an engulfing cell state. As the mechanisms of engulfment are highly conserved, these findings will have implications for the understanding and treatment of human diseases, including neurodegenerative and auto-immune disorders.

描述（由申请人提供）：有效去除死细胞是动物发育和体内平衡的重要过程。细胞尸体经常被巨噬细胞等专业吞噬细胞吞噬。然而，一些组织对循环细胞的可及性有限，并且吞噬是由邻近的非专业吞噬细胞（例如上皮细胞）进行的。细胞尸体识别、吞噬和吞噬体分解的机制仅被部分了解。果蝇卵巢为研究非专业吞噬细胞的吞噬提供了一个极好的系统。卵巢对循环细胞关闭，饥饿很容易引起整个卵室的退化。在这种退化的卵室中，生殖细胞被周围的体细胞卵泡细胞吞噬。这种吞噬过程在细胞死亡开始时同步且快速地发生，然而滤泡细胞吞噬的遗传要求完全未知。该提案旨在确定毛囊细胞吞噬所需的基因和途径。首先，将研究已知的吞噬基因和候选信号分子在毛囊细胞吞噬中的作用。其次，将分离吞噬滤泡细胞，并使用 DNA 微阵列和蛋白质组学方法将其表达谱与非吞噬滤泡细胞进行比较。第三，将进行遗传筛选以确定新的吞噬基因。通过这些方法鉴定的基因将因其在毛囊细胞和其他组织吞噬中的作用而被表征。这些发现有望揭示上皮细胞切换到吞噬细胞状态所需的信号传导机制。由于吞噬机制高度保守，这些发现将对人类疾病的理解和治疗产生影响，包括神经退行性疾病和自身免疫性疾病。