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Physiology and pathology of microglia development and functions – role of transcriptional (re)programming by retinoid receptors
Réf ABG-125930Stage master 2 / Ingénieur
Durée 6 mois
Salaire net mensuel 600
21/09/2024
IGBMC Institut de Génétique et de Biologie Moléculaire et Cellulaire CERBM - GIELieu de travail
Strasbourg/Illkirch Graffenstaden Grand Est France
Champs scientifiques
- Biologie
- Psychologie, neurosciences
- Santé, médecine humaine, vétérinaire
microglia, neurodegenerative diseases, depression, adaptative mechanisms, nuclear receptors, vitamin A
Établissement recruteur
Site web :
http://www.igbmc.fr/en/recherche/teams/brain-development-and-physiology
The project will be carried out at the IGBMC (Strasbourg-Illkirch), an international research institute located in the heart of a dynamic research region at the crossroads of France, Germany and Switzerland. It will benefit from state-of-the-art infrastructures, technical platforms and their expertise, as well as ongoing local and international collaborations.
Description
Microglial cells (MGCs) are endogenous brain macrophages of myeloid origin indispensable for normal brain development, functions and healthy aging (Borst et al., Immunity 2021). Recent studies (Hammond et al., Immunity 2019) indicated the existence of a high diversity within parenchymal microglial cells, which depends on sex, age, localization or pathological condition.The key molecular determinants of this heterogeneity and its pre- or postnatal origin are yet to be characterized. Likewise, dynamics of the myeloid populations during aging and pathological conditions remains largely unexplored.
Nuclear hormone receptors are a family of transcriptional factors, acting as master regulators of transcriptional programs underlying cellular proliferation, differentiation and homeostasis. Many of those receptors are modulated by their cognate ligands, opening numerous possibilities of nutritional or pharmacological modulation (Krezel et al., Mol Cell Endocrinol. 2019; Krzyzosiak et al., Neurobiol Stress. 2021). Although retinoid receptors are well known for their multiple developmental functions including ontogenesis of different neural cell types, little is known about their role in ontogenesis of MGCs.
The project will focus on characterizing the role of retinoid receptors in MGC development and homeostasis during adult life, and will be associated with functional analyses of different subtypes of MGCs. Dedicated genetic mouse models available in the team will be used throughout the project which will combine cell-fate tracing techniques, immunohistochemical and transcriptomic analyses (e.g. single cell RNAseq), primary cell and organotypic cultures.Relevance of obtained molecular and cellular data for neurodevelopment or neurodegeneration is already suggested by human genetic studies and could be further studied in the follow-up Ph D project using human material and selected mouse models relevant for example for multiple sclerosis and depression.
Expertise will be acquired in the fields of neuroimmunology, developmental biology, genetics, molecular and cellular biology, cell/organotypic cultures and imaging methods at the cellular level (live imaging, immunostaining, in situ hybridization, etc).
Profil
This project is dedicated for M2 training students (M1 training candidates are also welcome to apply). Good level of English, high motivation for translational studies using in vivo and in vitro techniques applied to mouse models, rigor, and dynamic contribution to the life of the team.Sound knowledge of developmental biology or immunology will be important, preliminary experience in basic cellular and/or molecular biology techniques or confocal or life imaging will be appreciated.
Prise de fonction
Dès que possible