The primary objective is to clarify species-specific differences in physiology and sensitivity to thyroid hormone system-disrupting chemicals and their mixtures. This research will employ a comparative physiology approach, utilizing both transgenic eleuthero-embryonic models of fish and amphibians, as well as human in vitro assays. Initially, the doctoral candidate will investigate variations in sensitivity among these models to reference thyroid hormone system-disrupting chemicals with well-characterized modes of action. Following this, the study will investigate the synergistic or
additive effects of chemicals with different modes of action on the thyroid hormone system in vivo and in vitro. This will involve testing mixtures of two or three chemicals with distinct mechanisms, such as a thyroid hormone transporter inhibitor combined with a thyroid receptor antagonist or a deiodinase inhibitor paired with sodium-iodide symporter inhibitors. Additionally, the well-documented interaction between glucocorticoids and thyroid hormones in certain species will be explored using these models. This will be achieved by testing mixtures of thyroid hormone system-disrupting chemicals with modulators of the glucocorticoid system, as well as real-life chemical mixtures.
- Host Institution: Watchfrog, France
- Lead Supervisor: David Du Pasquier, Watchfrog
- Subject area: Aquatic embryos, thyroid disrupters, comparative physiology