Analysis of human normal thyroid organoids response to ionizing radiation
Il y a 5 mois
Mission
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the dose and the frequency of spontaneous thyroid cancers increases with age, statistical epidemiological methods are no longer applicable.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 Cs 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.
Profil recherché
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.
Télétravail
Occasionnel
Informations complémentaires
The start date is fixed from september . The duration of the position is 18 months and it will be located at the Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses , France. Salary will be based on qualifications and experience according to the IRSN salary grid. Applications will be considered until the position is filled.
Applicants are encouraged to submit their CV, a short research statement, at least one manuscript (published or unpublished) and the names of 2-3 reference persons.
Please send applications and potential enquiries to Catherine Ory () and to Maâmar Souidi ()
Diversité
La diversité est une des composantes de la politique RSE, RH et Qualité de Vie au Travail à lIRSN. 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 dun 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.
Localisation du poste
Localisation du poste
Europe, France, Ile-de-France, Hauts-de-Seine
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Nanterre, Île-de-France IRSN Temps pleinMissionScientific ContextThyroid exposure to ionizing radiation during childhood is a recognized risk factor for the development of cancers. However, the risk decreases with the dose, and statistical epidemiological methods are no longer applicable. To address this knowledge gap, we are developing an organoid model derived from human normal thyroid tissue,...
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Nanterre, Île-de-France IRSN Temps pleinJob DescriptionScientific ContextIonizing radiation exposure to the thyroid gland during childhood has been identified as a risk factor for cancer development. However, the impact of low-dose exposure on public health remains unclear. To address this knowledge gap, we are developing an organoid model of human normal thyroid tissue, which reproduces the 3D...
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Nanterre, Île-de-France IRSN Temps pleinScientific ContextIonizing radiation exposure to the thyroid gland is a recognized risk factor for cancer development, particularly at high doses. However, the impact of low-dose exposure on thyroid organoids remains unclear. To address this knowledge gap, we are seeking a researcher to investigate the effects of ionizing radiation on human thyroid...
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