From Rare Diseases to Common Mechanisms of
Il y a 2 mois
**From rare diseases to common mechanisms of neurodegeneration**:
- Réf
- **ABG-114542**
- Sujet de Thèse- 17/05/2023- Contrat doctoral- IGBMC- Lieu de travail- Strasbourg - Grand Est - France- Intitulé du sujet- From rare diseases to common mechanisms of neurodegeneration- Champs scientifiques- Biologie
- Santé, médecine humaine, vétérinaire
- Mots clés- neurodegeneration, gene therapy, striatum, dopamine, rare disease, retinoic acid**Description du sujet**:
- MCOPS12 is a rare disorder characterized by developmental eye defects and neurodegenerative symptoms related to motor and cognitive functions. The disease is caused by monoallelic variants in the gene coding for the retinoic acid receptor beta (RARB). Pathogenic variants in
- _RARB_ occur mainly
- _de novo_ but can also be inherited;
- _de novo_ mutations are associated with a more severe neurological phenotype than inherited ones. The main concerns reported by clinical teams and MCOPS12 families are neurologic impairments.- RARB is a member of the nuclear receptor family and acts as ligand-regulated transcription factor. Together with other retinoic acid receptor isotypes (RARa and RARg) it mediates signaling of retinoic acid (RA) an active form of vitamin A, which is indispensable for the development of the central nervous system in all vertebrates. The knowledge on its postnatal functions, classically associated with vision, only starts being discovered and expands rapidly since the last decade. Importantly, compromised RA signaling and in particular RARb expression has also been associated with several other neurodegenerative diseases including Huntington’s disease, amyotrophic lateral sclerosis or Parkinson’s disease. Thus, studying mechanisms of MCOPS12 neurodegeneration should shed light onto mechanisms of other diseases too.-
**Prise de fonction**:
- 02/10/2023**Nature du financement**:
- Contrat doctoral**Précisions sur le financement**:
- funding to be obtained through doctoral school competition**Présentation établissement et labo d'accueil**:
- IGBMCThe project will be carried out at IGBMC and Mouse Clinical Institute (Strasbourg-Illkirch), international research institutes located in the heart of dynamic research region at crossroads of France, Germany and Switzerland. It will benefit from such location and state-of-the-art infrastructure and expertise in animal behavior and pharmacology, molecular, genomic and bioinformatics analyses.
**Intitulé du doctorat**:
- Doctorat en neurosciences**Pays d'obtention du doctorat**:
- France**Etablissement délivrant le doctorat**:
- UNIVERSITE DE STRASBOURG**Ecole doctorale**:
- Sciences de la vie et de la santéExpertise which will be acquired during the training: Conduct a research project including participation to the design of experiments, critical analysis of results, and presentation of results in lab meetings, writing publication(s). Expertise will be acquired in the fields of gene therapy, genetics, molecular and cellular biology, cell/organotypic cultures and various imaging methods at the cellular level (live imaging, immunostaining, in situ hybridization, etc).- 05/06/2023
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