Role of epigenetic changes in low dose radiation responses

了解低剂量电离辐射(IR)效应和体内适应性反应的分子机制一直是我的实验室的主要重点之一。在2003-2004年间，我开创了辐射表观遗传学领域的研究。这项研究计划试图继续更详细地阐明当生物体暴露在低剂量的IR中时，在更高水平的生物组织中观察到的表观遗传反应。表观遗传学的三个主要领域-DNA甲基化和氢化甲基化、组蛋白修饰和小RNA介导的沉默-已知对控制基因表达具有深远的影响。虽然全球DNA甲基化在IR反应中的作用已被证明，但这种表观遗传现象的确切性质需要定义。此外，在DNA羟甲基化领域，IR效应的现象还没有被探索。此外，需要更详细地分析小RNA在低剂量IR反应中的作用。这项NSERC资助续期的主要长期目标是剖析诱导IR诱导基因组不稳定和适应性反应的分子表观遗传学基础，并确定表观遗传变化(即DNA甲基化、羟甲基化和小RNA)在这些现象中的特定和基本作用。我们将使用尖端的深度测序方法来表征甲基组和转录组，包括小RNA组。该项目将为几名研究生、本科生和博士后提供极好的培训机会。

Understanding the molecular mechanisms of low-dose ionizing radiation (IR) effects and in vivo adaptive responses has been one of the major focuses of my laboratory. In 2003-2004, I pioneered the studies in the area of radiation epigenetics. This research program seeks to continue elucidating in more detail the epigenetic responses observed in higher levels of biological organization when organisms are exposed to low doses of IR. Three major areas of epigenetics - DNA methylation and hydrohymethylation, histone modifications and small RNA-mediated silencing - are known to have profound effects on controlling gene expression. While the role of global DNA methylation in IR responses was shown, the exact nature of this epigenetic phenomenon needs to be defined. Furthermore, the phenomenon of IR effects has not been explored in the DNA hydroxymethylation domain. Additionally, the roles of small RNAs in low-dose IR responses need to be analyzed in more detail. The main long-term goal of the renewal of this NSERC grant is to dissect the molecular epigenetic basis of induction of IR-induced genome instability and adaptive responses and identify the specific and fundamental role of epigenetic changes (i.e., DNA methylation, hydroxymethylation and small RNAs) in these phenomena. We will use cutting-edge deep sequencing approaches to characterize methylome and transcriptome, including small RNAome. This project will provide excellent training opportunities for several graduate and undergraduate students and postdocs.