MetOxyRYR

BACKGROUND

RYR1-related myopathies are rare, neurodegenerative genetic diseases that currently have no cure. An original murine model has been developed, faithfully reproducing the symptoms observed in certain patients through a reduction in RYR1 expression. This model is therefore particularly well-suited for developing and evaluating new therapeutic strategies.

An increase in oxidative stress has been observed in the muscles of diseased mice. Treatment with an antioxidant significantly slowed down the loss of muscle strength. To better understand the molecular mechanisms responsible for this beneficial effect and to identify potential therapeutic targets, an in-depth analysis of the metabolic pathways affected by the treatment is planned using metabolomic techniques (NMR).

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STUDENT CONTRIBUTION

The student will actively participate in the project by carrying out the following tasks:

1. Experimental monitoring: management of cohorts of diseased mice, treated or untreated with an antioxidant, with regular evaluation of motor performance and muscle strength over a period of 2 months.
2. Sample collection: taking muscle and blood samples at the end of the protocol for metabolic analyses.
3. Sample preparation and analysis monitoring: preparing samples for NMR metabolomic analyses (within GIN) and tracking experiments.
4. Data analysis: processing and interpretation of metabolomic results.
5. Muscle histology: performing histological stainings on muscle sections to correlate metabolic data with muscle structure.