Genetic screens for IR resistance

IR 抗性基因筛选

• 批准号: 7054545
• 负责人: STEPHEN J ELLEDGE
• 金额: $ 46.64万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054545
• 关键词: RNA interference; apoptosis; cell cycle; cell proliferation; gene induction /repression; genetic library; genetic screening; ionizing radiation; radiation genetics; radiation protection; radiation resistance; radioprotective agents; reporter genes; stem cells; tissue /cell culture

The overall aim of this project is to identify genes, primarily through genome-wide RNAi screens and cDNA library over-expression, that can act as potential drug targets to promote the survival of organisms irradiated with a dose of irradiation capable of destroying their hematopoetic system. We will probe different aspects of survival in response to IR including direct survival, resistance to oxidative stress, the control of hematopoetic stem cell proliferation and differentiation, and apoptosis control. We will also screen for chemicals that disrupt the major known checkpoint pathway known to cause killing in response to IR and for inhibitors of proteins identified in our RNAi screens, in order to identify molecules that can prolong survival after exposure to ionizing radiation. We will investigate the pathways involved in radio-resistance genetically and chemically with the goal of finding drugs and drug targets that will promote survival of people who have undergone potentially lethal irradiation.

该项目的总体目标是主要通过全基因组RNAi筛选和cDNA文库过表达来鉴定基因，这些基因可以作为潜在的药物靶点，以促进受到能够破坏其造血系统的辐射剂量照射的生物体的存活。我们将探讨生存的不同方面，包括直接生存，抗氧化应激，造血干细胞增殖和分化的控制，凋亡控制。我们还将筛选破坏已知的主要检查点通路的化学物质，这些通路已知会导致IR反应中的杀伤， 在我们的RNAi筛选中鉴定的蛋白质，以鉴定暴露于电离辐射后可以延长存活的分子。我们将研究涉及辐射抗性的遗传和化学途径，目的是找到药物和药物靶点，以促进经历过潜在致命辐射的人的生存。