The research project relies on a closed collaboration between the IRSN (Radiobiology of Accidental Exposure Laboratory (LRAcc, SERAMED, IRSN) and the CEA (Institute of cellular and molecular radiobiology).  Experimental research will take place in the LRAcc which develops operational methods and tools used for the diagnosis and prognosis of radiation-induced organ damage.

The Institute for Radiation Protection and Nuclear Safety (IRSN) is the French public expert, with industrial and commercial activities, in nuclear and radiation risks, and its activities cover all the related scientific and technical issues. The Institute is supervised jointly by the French Minister of the Ecological transition, the French Minister of Defense, and the French Ministers of Energy transition, Research and Health.

The Atomic Energy and Alternative Energies Commission (CEA) is a research organization specializing in the fields of nuclear and renewable energies (low carbon), defense and security, technological research for industry and fundamental research (material sciences, natural sciences of life and health). The CEA is a public industrial and commercial establishment (EPIC) placed under the triple supervision of the Ministry of Ecology, the Ministry of Higher Education and the Ministry of the Armed Forces.

Scientific context
Thyroid exposure to ionizing radiation (IR) during childhood, following radioactive iodide contamination or external exposure is a recognized risk factor for the development of cancers by epidemiology studies, but for thyroid doses above 50mGy. As the risk decreases with the dose and the frequency of spontaneous thyroid cancers increases with age, statistical epidemiological methods are no longer applicable. In addition, no specific clinical, anatomo-pathological or genetic criterion distinguish radiation-induced from spontaneous thyroid tumors. Therefore, to date, we cannot objectively answer to scientific and societal questioning concerning the impact on public health of an exposure to the thyroid at low doses.

Work context and objectives
We are developing an organoid model (thyrospheres), derived from human normal thyroid tissue, reproducing in matrigel the 3D organization of thyroid follicles, the functional units of the tissue. We now have culture conditions that permit to maintain follicular 3D structure which synthesize the thyroid hormone thyroxine in the lumen, the thyrocytes responding to a thyroid-stimulating hormone stimulation for the release of the hormone into the culture medium up to seven weeks.

The candidate will be involved in the analysis of the organoïds response to low doses of RI. The thyrospheres will be exposed to low doses as compared to doses known to be associated with the development of radiation-induced thyroid cancers. Exposure will be realized at the CEA irradiation platform to 137Cs gamma sources (GSR-D1 irradiator) allowing exposures over a wide range of doses including lowdoses. Results published in the literature or obtained in our laboratory strongly suggest that a mechanism of induction/adaptation to oxidative stress could be a major key step in radiation-induced thyroid carcinogenesis. Thus, at first intention the candidate will develop protocols focused more particularly on the analysis of the oxidative status of the organoids after exposure: exploration of key signaling pathway, of mitochondrial function and reactive oxygen species production, and metabolomic approaches will be developed in collaboration with the laboratory of T. Pourcher (TIRO, CEA, Nice).

The candidate will be also involved the long-term maintenance of thyrospheres in culture. The objective is to be able to follow the response to IR over the longest culture period to analyze possibly the early steps of carcinogenesis. The culture process should maintain the organoids 3D structure and physiology over times. Methodologies to monitor the maintenance of expression and the correct localization of thyroid differentiation markers (immuno-labelling, RT-PCR), and to measure the synthesis function of T4 (immuno-labelling and T4 dosage) are routinely applied in our laboratory.

Applicants should have a PhD in molecular and cellular biology. A good experience in cell culture and knowledge of the molecular mechanisms of the cellular response to genotoxic stress will be appreciated. The selected candidate will be encouraged to present the findings of the project at scientific conferences as well as to administrative authorities.

La diversité est une des composantes de la politique RSE, RH et Qualité de Vie au Travail à l’IRSN. Nous accordons la même considération à toutes les candidatures, sans discrimination, pour inclure tous les talents.

Quelles que soient les différences, nous souhaitons attirer, intégrer et fidéliser nos candidats et nos collaborateurs au sein d’un environnement de travail inclusif.

L'IRSN conduit une politique active depuis de nombreuses années en faveur de l'égalité des chances au travail et l'emploi des personnes handicapées. Si vous êtes en situation de handicap, n'hésitez pas à nous faire part de vos éventuels besoins spécifiques afin que nous puissions les prendre en compte.