Genetics/Cell Biology of Anoxia in C.elegans

线虫缺氧的遗传学/细胞生物学

• 批准号: 7116907
• 负责人: Pamela Anne Padilla
• 金额: $ 19.08万
• 依托单位: UNIVERSITY OF NORTH TEXAS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7116907
• 关键词: Caenorhabditis elegans; RNA interference; cell biology; cell cycle; cell growth regulation; cytogenetics; fluorescence microscopy; hypoxia; oxygen; polymerase chain reaction; recombinant proteins

DESCRIPTION (provided by applicant): Extreme oxygen deprivation is central to the pathology of several diseases involving cardiac and pulmonary dysfunction. Oxygen deprivation also plays a role in the resistance of solid tumors to radiation or chemotherapy treatment. Understanding the genetic and cellular response oxygen-deprivation resistant organisms have to anoxia, hypoxia will facilitate the development of treatment for the rescue of damaged ischemic tissue, or the destruction of oxygen deprived tumor cells. We found that the nematode C. elegans is capable of surviving prolonged exposure to anoxia (<.001 kPa Oxygen). Embryos exposed to anoxia leads to a complete arrest of cell cycle and developmental progression. Upon reexposure to oxygen, these processes are resumed. The long-term goal of this research is to characterize the molecular and cellular responses nematodes have to oxygen deprivation. The central hypothesis of this application is that embryos contain a genetic program to coordinate the arrest of biological processes such as cell division in response to anoxia. Previously, we found that the spindle checkpoint is required for embryos to arrest blastomeres in metaphase during exposure to anoxia. We will use a combination of genetic and cell biological techniques to further investigate the pathway between oxygen deprivation and cell division arrest in the nematode embryo by pursuing the following aims. Aim 1. Examine the response the spindle checkpoint components have in embryos exposed to anoxia. Previously we found that the spindle checkpoint components (san-1 and mdf-2) are required for embryos to survive anoxia. We will use genetic and cell biological techniques to expand on this finding. Aim 2. Use RNA interference to identify genes that are not required for embryo development, but are required for embryos to survive anoxia. Cell biological techniques will be used to determine if these gene products are required for blastomeres to arrest the cell cycle in response to anoxia.

描述（由申请人提供）：极端缺氧是涉及心肺功能障碍的几种疾病病理的核心。缺氧也在实体瘤对放疗或化疗的抵抗中起作用。了解抗缺氧生物对缺氧的遗传和细胞反应，将促进缺氧治疗的发展，以拯救受损的缺血组织，或破坏缺氧的肿瘤细胞。我们发现秀丽隐杆线虫能够长时间暴露于缺氧（< 0.001 kPa氧气）中存活。胚胎暴露于缺氧导致细胞周期和发育进程完全停止。一旦再次暴露于氧气中，这些过程就会重新开始。本研究的长期目标是表征线虫对缺氧的分子和细胞反应。这一应用的中心假设是，胚胎包含一个遗传程序，以协调生物过程的停止，如细胞分裂，以应对缺氧。先前，我们发现纺锤体检查点是胚胎在暴露于缺氧的中期阻止卵裂球所必需的。我们将利用遗传和细胞生物学技术的结合，进一步研究缺氧与线虫胚胎细胞分裂停滞之间的途径，实现以下目标。目的1。检查胚胎暴露于缺氧时纺锤体检查点成分的反应。先前我们发现纺锤体检查点成分（san-1和mdf-2）是胚胎在缺氧条件下存活所必需的。我们将使用遗传和细胞生物学技术来扩展这一发现。目标2。使用RNA干扰来识别胚胎发育不需要的基因，但是胚胎在缺氧条件下生存所需要的基因。细胞生物学技术将用于确定这些基因产物是否是卵裂球在缺氧条件下抑制细胞周期所必需的。