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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要父亲线粒体消除和辐射引起的旁观者效应是两个至关重要的，不同的，以及动态生物学过程对于动物发育，压力反应和有机体适应性至关重要。这两个重要过程中的缺陷会导致各种病理状况和疾病。在这个拟议的工作，我们将进行分子遗传，反向遗传，生化，细胞生物学和蛋白质组学分析以解密调节父亲线粒体消除和辐射诱导的基本机制旁观者效应。为了研究父亲的线粒体消除，我们希望了解父亲如何线粒体在受精卵中有选择性地受损，识别和去除，父亲和母亲是什么采用机制专门消除父亲的线粒体，以及为什么父亲线粒体需要拆除以确保动物发育，细胞和生物健康。用于辐射研究诱发的旁观者效应，我们计划确定触发未受未暴露的旁观者效应的因素细胞，介导不同旁观者反应的信号途径以及旁观者的机理基础对其他压力的反应。这些研究应揭示控制的新机制，途径和基因这两个基本的生物学过程，最终提供了新的目标，思想和策略促进由父亲线粒体消除异常引起的许多人类疾病的治疗并通过减少放射疗法和其他治疗性引起的副作用来改善疾病治疗治疗。