Role of polyunsaturated fatty acids in human microglia maturation during neurodevelopment

id="offer-description" class="ecl-u-type-heading-2 ecl-u-mt-none ecl-u-mb-l">Offer Description Microglia, the resident immune cells of the brain, play an essential role in neurodevelopment by clearing apoptotic cells and contributing to neuronal circuit refinement. Polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA, omega-3) and arachidonic acid (AA, omega-6), are critical for brain development and cellular signaling (Martinez et al., 1992). Although previous studies have demonstrated that dietary omega-3 PUFA deficiency alters microglial functions and brain development in mice (Madore et al., 2020), the mechanisms through which PUFAs regulate human microglial maturation remain largely unexplored. The project aims to characterize PUFAs metabolism during human microglial maturation and determine its contribution to microglial development and functions. The candidate will use 2D and 3D-cellular models (human induced pluripotent stem cell (iPSC)-derived microglia & developing cerebral organoids) and humanized and transgenic mouse models. Experimental approaches will include CRISPR-Cas9 genome editing, lipidomics, RNA sequencing, flow cytometry, immunohistochemistry, RNAscope, functional assays such as multielectrode array and behavioural testing. We are seeking a highly motivated PhD candidate to investigate the role of PUFAs in human microglial maturation during brain development. This 36-month PhD project, funded by INRAE and the French National Resear