PhD position in endocrine disruption focusing on thyroid hormone and brain development
Team: “Integration of transcriptional responses inducted by thyroid hormones and their receptors” (Pr. Demeneix). Our work is focused on understanding how thyroid hormone signalling is integrated in different physiological situations from early brain development to ageing. >> More information
Organisation: UMR 7221 Evolution of Endocrine Regulations (CNRS/MNHN)
The overarching objective of the research unit is to understand the physiological regulations that control development, tissue homeostasis, regeneration and aging. To this end we take advantage of comparative approaches with a developmental and evolutionary outlook. We apply the growing array of genomic tools of molecular physiology, to analyse regulations that support integrated responses at the level of the organism. >> More information
Since the 1990’s overwhelming evidence has accumulated that the presence of small quantities of certain chemicals during the stages of embryonic development may alter the physiology of vertebrates, including humans. Because these chemicals can interfere with development by disrupting the function of the hormonal system, they are called endocrine disruptors.
Adverse outcome pathways leading to disorders such as abnormal male gonadal development, infertility, ADHD, autism, diabetes, thyroid disorders, and childhood or adult cancers have increased and could be linked to fetal chemical exposure. Owing to the crucial role of fine-tuned thyroid hormone levels for normal neural cell fate decisions and normal brain development, one of our main hypothesis that thyroid disruption is linked to neurodevelopmental diseases.
Whilst data exist for such individual chemicals, few studies have addressed effects of mixtures, which reflect a more realistic exposure. Another crucial point is to understand the causality link between exposure and adverse long lasting effects via endocrine disruption. Our team is investigating short and long-term effects of early exposure to chemical mixtures, on endocrine set points occurring during embryogenesis. The PhD project will be integrated in a more general context of a European project with human samples obtained perinatally from pregnant mothers or from their children.
Financed as part of the HBM4EU European project, the candidate will carry out work within this human biomonitoring project notably determining and testing the pertinence of biomarkers of effects. Part of the work will use an OECD validated assay, Xenopus Embryonic Thyroid Assay (XETA). To this end the candidate will test potential thyroid hormone disruptive effect of mixture of chemicals using XETA and will study short and long term consequences on gene expression (using both large scale and gene candidate approaches on brain and other tissues) and general physiology of an embryonic exposure during sensitive windows of development. Complex matrixes such as human samples could also be tested with the overall aim of determining biomarkers of effect.
Motivated applicants should fulfill the following criteria:
• Solid background in endocrinology, (thyroid hormone would be a plus) and molecular biology
• Knowledge of endocrine disruption, neurodevelopment in vertebrates
• Comparative genomic data analysis skills
First experience with either immunohistochemistry in aquatic models or large-scale data analysis would be a plus.