EPIGENETIC MECHANISMS OF TOXICITY AFTER DEVELOPMENTAL EXPOSURE TO MARINE TOXINS

The overall objective of the proposed research is to elucidate the molecular Mechanisms by which short-term Exposure to harmful algal bloom (HAB) Toxins and marine toxicants during Development causes physiological and neurological abnormalities later in life. It is now well known that the early life environment can have a profound effect on the health of adults (the Developmental origins of health and disease). However, the Mechanisms by which Developmental Exposure elicits effects later in life are not understood. The central hypothesis of this research is that embryonic Exposure to certain marine Toxins or toxicants alters Epigenetic programming, leading to long-term effects on gene expression in adult tissues and ultimately contributing to altered neurobehavioral function in adults. We will conduct studies to identify a core set of genes that show long-term transcriptional changes due to changes in the early life chemical environment and identify their Epigenetic signature to determine the mechanistic link between adult phenotype and early life exposures. These studies will be conducted using zebrafish, a powerful model organism for research on Developmental Mechanisms. In Aim 1, we will test the hypothesis that Developmental Exposure to HAB Toxins (Saxitoxin, domoic acid) and toxicants (PCB126, PCB153) causes later life changes in gene expression and behavior. In Aim 2, we will test the hypothesis that adult effects resulting from Developmental Exposure to HAB Toxins and toxicants are caused by Epigenetic reprogramming of gene expression, focusing on altered DNA methylation and microRNA expression. In Aim 3, we will determine whether the proximal Mechanisms involving receptors and ion channels known to be responsible for the acute effects of these chemicals are also involved in the delayed effects seen in adults exposed to chemicals during Development. This research will identify molecular bases for adult effects occurring after Developmental Exposure to important HAB Toxins and marine toxicants, and determine whether there are similar or convergent Epigenetic Mechanisms involved.