Project 3: Cellular and molecular mechanisms underlying effects from early life exposure to HAB toxins

The research will investigate the neurodevelopmental toxicity of HAB toxins using two complementary model systems: transgenic zebrafish embryos (in vivo) and human iPSC-derived 3D brain systems (in vitro). Aim 1 will use single-cell RNA sequencing in zebrafish to study how domoic acid affects oligodendrocyte-neuron interactions, how saxitoxin alters extracellular matrix at synapses, and how anatoxin-a causes nervous system deficits by activating nicotinic acetylcholine receptors. Aim 2 will use human iPSC-derived neuronal cultures to investigate the effects of HAB toxins on neuronal and glial cell differentiation. Aim 3 will test the hypothesis that combined early life and preconceptional exposure to low levels of PCBs influences responses to HAB toxins. Aim 4 will utilize probabilistic models to assess human exposure to domoic acid and collaborate with other projects to predict human exposure to saxitoxin and domoic acid using coupled HAB biophysical and exposure models.