PhD Student in immunotoxicity and neurotoxicity associated with early-life exposure to environmental pollutants

Background and Research Environment. The IEE Research Group focuses on elucidating the molecular, immune and epigenetic mechanisms that link the early-life exposome to negative lifelong health trajectories (developmental origins of health and disease). The team are particularly interested in the long-term effects of early-life exposure to adversity such as pollutants, abuse, and poor psychosocial and socioeconomic conditions. In order to understand the long-term consequences of such negative conditions in early life, we use an interdisciplinary holistic approach, integrating data from multiple physiological systems to understand how the early-life environment induces a lifelong-programmed phenotype. Our work depends upon successful collaborations with toxicologists, immunotoxicologists, neurotoxicologists and psychobiologists to develop research aiming at characterizing new NAMs addressing three major endpoints in immunotoxicity and neurotoxicology;

Objectives: The PhD candidate will address the role of Natural Killer cells in immunosuppression based on previous human studies highlighting that these cells are durably altered in adulthood in individuals having been exposed early in life to bisphenol analogues compared with respective-free control subjects. In vitro, he/she will use NK cells derived from Human CD34+ Hematopoietic Stem Cells to investigate how bisphenol analogues, alone or in mixture, trigger immunosuppression/induce immunotoxicity, through an unbiased screening tool for flow cytometry data visualization, viSNE. The candidate will specifically address the NK immune cell population immunophenotyping and its functionality (cytotoxicity and degranulation response assessment). An in vivo study, based on our established rat models of immuno- and neurodevelopmental toxicity will be performed on a selection of BPA analogues inducing NK-cell immunosuppression to (i) validate the suitability of our in vitro model at modelling an Early-Life Adversity and (ii) to investigate by which mechanisms the immune system becomes impaired after early-life exposure to these BPA analogues. The shift on the senescent state of NK cells will be targeted.

Relevant recent publications

Morel et al., Environ Chem Lett. https://doi.org/10.1007/s10311-022-01392-

Morel et al., Toxics, 10, 180. https://doi.org/10.3390/toxics10040180

Fernandes et al., Frontiers in Immunology 2021. https://pubmed.ncbi.nlm.nih.gov/34394074/

Grova N. et al., International Journal of Genomics 2019 https://doi.org/10.1155/2019/2085496

Key Skills, Experience and Qualifications

• Master’s degree in Biomedical Sciences, Biology, Medicine, or other related fields
• Curious as to how we adapt to our environment, and the developmental origins of health and disease
• Interested in working in a truly international and interdisciplinary project team
• Independent and self-motivated person, scientific creativity and originality, strong team spirit and collaborative capacity, excellent time management, rigour, perseverance, strong writing skills.
• Fluency in English is mandatory

The successful candidate will join a highly dynamic research environment and get access to several core facilities and relevant state-of-the-art technologies. S/he will benefit from an active seminar program, international conference attendances and opportunities to collaborate with toxicologists, immunotoxicologists, neurotoxicologists, and psychobiologists.

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