Grant: Discovery Grants Program - Individual

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. Besides uncovering the mechanisms and revealing the molecular epigenetic networks involved in IR responses, the current project will address a fundamentally important issue: are small doses of environmental IR dangerous for living organisms? Evaluating the hazards of environmental exposure is especially important nowadays, after the Fukushima radiation accident. Understanding the molecular changes that occur in exposed cells may assist in the development of measures to prevent the deleterious effects of IR. In the future, the results obtained using the mouse model system can potentially be extrapolated to other animals and humans.