Determining the lasting impact on the developing epigenome by gestational toxic exposures

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Geno-toxicity, whereby a toxic compound causes changes to the genetic code through mutation, has received widespread attention from the research community. Effects of toxic insults on the epigenome, where the genetic code is not directly affected, instead the ability to correctly read this code, remain poorly understood. The programme focusses on developing our understanding of the action and mechanism of chronic sub-toxic insults on the epigenome. These occur when a substances dose is insufficient to cause acute toxicity, but instead alters the environment of the DNA. The programme will have a particular emphasis on the lasting impact of these exposures during pregnancy. These toxic events can be environmental or pharmaceutical, and we aim to identify similarities and differences in such diverse challenges. We employ standard genomics and molecular biology techniques, in addition to using a new approach to studying epigenetics. We have generated a series of transgenic mouse lines, which can “see” the epigenetic status of a gene, through imaging of a mouse in vivo. Using these approaches, we can track epigenetic change through life-course and across generations, thereby “seeing” the toxic insult in its entirety.