Deciphering Vitamin a Metabolic and Signaling

Il y a 4 mois


Strasbourg, France IGBMC Institut de Génétique et de Biologie Moléculaire et Cellulaire CERBM - GIE Temps plein

**Deciphering vitamin A metabolic and signaling pathways in the brain using biorthogonal chemistry-based strategies**:

- Réf **ABG-125758**
- Stage master 2 / Ingénieur- Durée 6 mois- Salaire net mensuel 600- 10/09/2024- IGBMC Institut de Génétique et de Biologie Moléculaire et Cellulaire CERBM - GIE- Lieu de travail- Strasbourg/Illkirch Grand Est France- Champs scientifiques- Biologie
- Biotechnologie
- Mots clés- vitamin A signaling, neurodegeneration, primary neural cell cultures, click reaction, confocal imaging, image anayses**Établissement recruteur**:
**Site web**:

- 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, as well as ongoing international collaborations. Multidisciplinary project will also allow contacts with biological chemists and participation in biological chemistry meeting.**Description**:
Vitamin A (retinol) is a micronutrient critical for normal development and physiology in vertebrates. Both, vitamin A deficiency or excessive exposure to retinoids (i.e., natural and synthetic analogues of retinol and its metabolites) are threats to human health and are either causal factors or contribute to physiopathology of a large number of diseases. The pleiotropic functions of vitamin A require highly regulated and multilevel control of its availability, metabolism, and signaling. Although these processes have been quite widely studied, the existing knowledge does not allow their full understanding. In the team we aim to better understand the molecular basis of retinoid metabolism and signaling, including its storage and transport in physiological and pathological conditions. The objective of present M2 project will be to use click chemistry to react purpose-tailored retinol and its metabolites with existing and newly developed dedicated functional fluorescent probes, in order to image retinoid transport and storage at the tissue, cellular and subcellular levels. The project will benefit from recently synthesized in collaboration with the team of Dr Alain Wagner chemolibrary of retinoids carrying a biologically inert azide or alkyne group making them amenable for click-chemistry reactions with chemical probes (see ref: DOI: 10.1002/cbic.202300689). Experiments will be focused primarily on nervous system, in which retinoid signaling was clearly documented, yet little explored and understood. Specifically, primary cultures of neurons and glial cells from wild-type mice and mouse models Huntington’s disease, known for deregulated retinoid signaling, will be used to compare dynamics and compartmentalization of retinoid storage and traffic. Preparation of primary cell cultures, live confocal imaging of cultured cells, immunofluorescent detection of cell-types and organelles together with image analyses will be essential toolbox during this project.

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