Analysis of Cell Death Regulation in C.elegans

线虫细胞死亡调控分析

• 批准号: 6840826
• 负责人: BARBARA CONRADT
• 金额: $ 34.28万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6840826
• 关键词: Caenorhabditis elegans; apoptosis; developmental genetics; gene expression; genetic regulation; germ cells; helminth genetics; hermaphroditism; in situ hybridization; molecular cloning

DESCRIPTION (provided by applicant): Programmed cell death or apoptosis is the process through which multicellular animals eliminate unwanted and potentially dangerous cells from their body. Deregulating programmed cell death in humans can lead to disease, such as various types of cancer, autoimmune diseases and neurodegenerative diseases demonstrating the importance of this process for human health. Studies performed over the last decade have resulted in the identification of the major components of the central, conserved machinery required to bring about programmed cell death. However, little is known thus far about how this central machinery is regulated. The long-term goal of our investigation is to determine how programmed cell death is controlled in the nematode Caenorhabditis elegans, genetic studies of which have been pioneering in the elucidation of the central cell death machinery. Our studies focus on the analysis of the programmed death of germ cells in the gonad of adult C. elegans hermaphrodites and the programmed death of two types of somatic cells, the NSM sister cells and the CEMs, during development. In order to identify factors involved in the regulation of these three cell death events, we have developed tools for their efficient detection. These tools we have used to identify C. elegans mutants defective specifically in germ cell death, the NSM sister cell death or the CEM death. The molecular characterization of the affected genes will provide insight into the nature of the mechanisms involved in activating the central cell death machinery in specific tissues or specific cells. Furthermore, we will analyze the function of the affected proteins and determine how they control the activity of the central cell death machinery. Since the pathways involved in regulating programmed cell death also seem to be conserved, results from these studies will improve our current understanding of cell death regulation not only in C. elegans but in higher organisms, including humans, as well.

描述（由申请人提供）：程序性细胞死亡或细胞凋亡是多细胞动物从体内消除不需要的和潜在危险的细胞的过程。 人类程序性细胞死亡的失调可能导致疾病，例如各种类型的癌症、自身免疫性疾病和神经退行性疾病，这证明了这一过程对人类健康的重要性。 过去十年进行的研究已经确定了导致程序性细胞死亡所需的中央保守机制的主要组成部分。 然而，迄今为止，人们对这一中央机制是如何监管的知之甚少。我们研究的长期目标是确定秀丽隐杆线虫中程序性细胞死亡是如何控制的，其遗传学研究在阐明中央细胞死亡机制方面处于领先地位。 我们的研究重点是分析成年线虫雌雄同体性腺中生殖细胞的程序性死亡，以及发育过程中两种类型体细胞（NSM 姐妹细胞和 CEM）的程序性死亡。 为了确定参与这三种细胞死亡事件调节的因素，我们开发了对其进行有效检测的工具。 我们使用这些工具来识别在生殖细胞死亡、NSM 姐妹细胞死亡或 CEM 死亡方面存在特异性缺陷的线虫突变体。 受影响基因的分子特征将有助于深入了解激活特定组织或特定细胞中的中央细胞死亡机制所涉及的机制的本质。 此外，我们将分析受影响蛋白质的功能，并确定它们如何控制中央细胞死亡机制的活动。 由于参与调节程序性细胞死亡的途径似乎也是保守的，因此这些研究的结果将提高我们目前对细胞死亡调节的理解，不仅在秀丽隐杆线虫中，而且在包括人类在内的高等生物中也是如此。