Fundamental mechanisms of paternal mitochondrial eliminationand radiation-induced bystander effects

父本线粒体消除和辐射诱导的旁观者效应的基本机制

• 批准号: 10631083
• 负责人: DING XUE
• 金额: $ 55.22万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631083
• 关键词: Animals; Biochemical; Biological; Biological Process; Bystander Effect; Cell physiology; Cells; Defect; Development; Disease; Ensure; Event; Genes; Human; Impairment; Inherited; Mediating; Mitochondria; Mitochondrial Diseases; Molecular Genetics; Normal Cell; Pathologic; Pathway interactions; Process; Proteomics; Radiation; Radiation therapy; Signal Pathway; Stress; Therapeutic; Work; biological adaptation to stress; fitness; human disease; improved; new therapeutic target; novel; response; reverse genetics; side effect; zygote

Project summary Paternal mitochondrial elimination and radiation-induced bystander effects are two vitally important, distinct, and dynamic biological processes essential for animal development, stress response, and organismal fitness. Defects in these two important processes can cause various pathological conditions and disease. In this proposed work, we will carry out molecular genetic, reverse genetic, biochemical, cell biological and proteomic analyses to decipher basic mechanisms that regulate paternal mitochondrial elimination and radiation-induced bystander effects. For the study of paternal mitochondrial elimination, we hope to understand how paternal mitochondria are selectively impaired, recognized and removed in fertilized eggs, what paternal and maternal mechanisms are employed to specifically eliminate paternal mitochondria, and why paternal mitochondria need to be removed to ensure animal development and cell and organismal fitness. For the study of radiation- induced bystander effects, we plan to identify factors involved in triggering bystander effects in unexposed cells, signal pathways that mediate different bystander responses, and the mechanistic basis of bystander responses to other stresses. These studies should reveal novel mechanisms, pathways, and genes that control these two fundamental biological processes, and ultimately, provide new targets, ideas, and strategies to facilitate treatment of numerous human diseases caused by abnormalities in paternal mitochondrial elimination and improve disease treatment by reducing side effects caused by radiotherapy and other therapeutic treatments.

项目概要 父系线粒体消除和辐射引起的旁观者效应是两个极其重要、不同的、 以及对于动物发育、应激反应和机体健康至关重要的动态生物过程。 这两个重要过程的缺陷会导致各种病理状况和疾病。在这个 拟议的工作，我们将开展分子遗传学、反向遗传学、生物化学、细胞生物学和蛋白质组学 分析以破译调节父系线粒体消除和辐射诱导的基本机制 旁观者效应。对于父系线粒体消除的研究，我们希望了解父系是如何消除线粒体的 线粒体在受精卵中选择性受损、识别和去除，父本和母本的线粒体 采用机制来特异性消除父本线粒体，以及为什么父本线粒体需要 被移除以确保动物发育以及细胞和有机体的健康。对于辐射的研究- 诱发旁观者效应，我们计划确定在未暴露的情况下引发旁观者效应的因素 细胞、介导不同旁观者反应的信号通路以及旁观者的机制基础 对其他压力的反应。这些研究应该揭示控制的新机制、途径和基因 这两个基本的生物过程最终提供了新的目标、想法和策略 促进治疗由父系线粒体消除异常引起的多种人类疾病 通过减少放射疗法和其他治疗方法引起的副作用来改善疾病治疗 治疗。