L’Oréal Advanced Research- Thèse CIFR position for the following subject:
THE FISH EMBRYO MODEL TO STUDY ENVIRONMENTAL AND HUMAN THYROID DISRUPTION
Our Advanced Research labs are offering a CIFRE scholarship opportunity to graduate students who wish to pursue a PhD.
1. Summary of the context:
Over the last decades, more and more chemicals have been suspected to impair environment and human health through endocrine mode of action. According to the OECD conceptual framework (2017), only in vivo animal tests identify adverse effects induced by endocrine disruption pathways. Testing on animals (as defined by Dir. 2010/63/UE) is not allowed in Europe for the safety assessment of cosmetic ingredients and low tonnage chemicals which must rely on alternative methods. The endocrine system (and the thyroid axis in particular) is highly conserved across vertebrate classes, from fish to mammals. Fish embryo models are highly popular in the areas of toxicology and ecotoxicology. In compliance with international animal welfare regulations, the fish embryo models provide an ethically acceptable small scale analysis system with the complexity of a complete organism.
Currently, no in vitro or in silico screening systems for Thyroid Disruption are currently available for high-throughput screening of chemicals.
This PhD thesis will be part of the collaborative research project named ERGO funded by the European Commission within the Horizon 2020 framework. This project aims to break down the wall between mammalian and non-mammalian vertebrate regulatory testing by identifying, developing and aligning thyroid-related biomarkers and endpoint for linkage of effects between different vertebrate classes. To achieve this, an AOP (Adverse Outcome Pathway) network covering various modes of Thyroid Disruption in multiple vertebrate classes will be developed.
• Identification of new potential new apical endpoints for Thyroid Disruption assessment in fish embryo models.
• Implementation of existing test guideline to assess Thyroid Disruption.
• Suggest new potential thyroid-related adverse endpoints to implement the fish embryo toxicity test (FET-OECD 236) based on bibliography and scientific papers review.
• Discuss protocol optimization in collaboration with the other partners of the ERGO projects.
Perform experiments on embryos of two fish species (Zebrafish and Medaka) from exposure to reference thyroid disrupter.
Assess morphology of said embryos and sample collection (cDNA, Tissue…).
• Perform sample analysis (qPCR, fluorescent quantification, histology).
• Contribute to results analysis to provide data to the others work package of the ERGO project.
Domain: developmental biology, Ecotoxicology, Endocrinology.
Primary skills: developmental biology, cell biology, molecular biology, communication in English.
Secondary skills: fish embryo experimentation, microscopy, image analysis and statistical analysis.