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Reference : UMR7221-LAUSAC0-001
Workplace : PARIS 05
Date of publication : Thursday, October 10, 2019
Scientific Responsible name : PhD in co-supervision: Laurent Sachs (DR CNRS) et Nicolas Buisine (MC MNHN).
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 January 2020
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
1. PhD thesis project:
The endocrine system orchestrates our physiological functions from conception onward. Over the last decades, an increasing number of chemicals have been suspected to impair environment and human health through endocrine mode of action. Endocrine disruptors (EDs) are defined as “exogenous substances or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub) populations.” Identified as a new type of health and environmental hazard, this issue requires to improve scientific knowledge in order to provide relevant EU regulations.
This PhD thesis will be part of the collaborative research project named ERGO and funded by the European Commission within the Horizon 2020 framework. The concept of ERGO is to improve hazard and risk assessment of EDs for protection of human health and the environment. ERGO aims to break down the existing walls between mammalian and non-mammalian vertebrate test models by demonstrating that it is feasible to extrapolate effects of EDs across vertebrate classes, i.e. an adverse effect on an endocrine-specific endpoint in a fish or amphibian would be predictive of potential adverse effects in human and will raise concern.
The PhD candidate will focus on the thyroid axis, a highly conserved endocrine system among vertebrates, and which biological significance is underscored in the ED test guidelines. Consequently, this limits our current hazard assessment of thyroid disrupting chemicals. EDs that affect thyroid hormone production, distribution or action can affect brain development and function, thus leading to increased incidence of neurodevelopmental disease together with strong societal and human cost.
In order to supply mechanistic understanding of thyroid disruption in vertebrates, the PhD candidate will carry out transcriptomic and methylome analyses in an amphibian embryo model. Amphibians are a well know system to study thyroid hormone signaling and a well-established model in the fields of toxicology and ecotoxicology. Transcriptomic analyses will contribute the identification of genes sensitive to ED exposure, and identify interference with the thyroid hormone system. Changes of DNA methylation patterns genome wide will be used to identify thyroid disruption-specific epigenetic changes. This set of data integrated in the context of the ERGO project will provide the molecular basis for the development of an adverse outcome pathway network, as well as new endpoints and molecular biomarkers and cross-class confirmation of molecular initiating events of thyroid disruption.
• Identification of new molecular initiating events for thyroid disruption in amphibian embryos.
• Suggest implementation of existing test guideline to assess thyroid disruption.
• Characterize biological impact of ED exposure on amphibian embryos with high throughput technologies (transcriptomic and methylome), from primary data production to processing and analysis.
• Contribute to data integration within ERGO to help extrapolate effects between all class of vertebrates.
• Suggest new potential thyroid-related adverse endpoints to implement the amphibian toxicity tests.
4. Candidate profile:
• Degree in: “Endocrinology” or “Molecular and Cellular Biology” or “Environmental toxicology” or “Ecotoxicology” will be considered.
• Primary skills: Experimental cellular and molecular biology, lab work interest, appetence for computer work, autonomy, scientific rigor, adaptability, communication and writing abilities, good communication in English.
• Secondary skills: experimentation on amphibians, high throughput data processing and analysis, statistical analysis.
The Joint Research Unit 'Molecular Physiology and adaption' (UMR 7221) affiliated with CNRS and the “Muséum National d'Histoire Naturelle”. The Unit is located on the “Muséum National d'Histoire Naturelle” campus in Paris (France). The CNRS (Centre National de la Recherche Scientifique) is a state-funded science and technology establishment placed under the authority of the French Minister for Research and Higher Education (www.cnrs.fr). The “Muséum National d'Histoire Naturelle” is a museum and research center created in 1635, with the mission to make knowledge about the natural world accessible to everyone and to make as many people as possible aware of the importance of protecting our planet. The main objective of the research Unit is to understand the physiological regulations that control development, tissue homeostasis, regeneration and aging in normal and altered conditions. The group's objective is to determine the physiological consequences of exposure to endocrine disruptors and environmental changes related to stress and life cycle transitions. The team develops two axes of research: 1) the evolution of molecular control of life cycle transitions with a special emphasis on amphibian metamorphosis, a post-embryonic developmental process that is initiated by thyroid hormones, 2) the impact of endocrine disruptors and stress on thyroid signaling.
ERGO aims to improve hazard assessment of EDCs for the protection of human health and the environment by breaking down the wall that currently exists between the different research fields that investigate adverse effects of EDCs in different vertebrate classes, from fish and amphibians (non-mammalian vertebrates) to humans (mammalian vertebrates) by demonstrating that it is feasible to extrapolate effects of EDCs across the vertebrate classes, i.e. an adverse effect observed in a fish or amphibian will also raise concern for an adverse effect in humans.
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