Reference : PhD Jocelyn Laporte
Congenital myopathies are severe genetic diseases that are characterized by muscle weakness at birth and the prevalence of specific histological abnormalities on muscle biopsy. These rare diseases are models to study the changes that occur with age, such as sarcopenia and the accumulation of skeletal muscle dysfunction. There is no specific therapy for these myopathies. In the team we concentrate on 2 classes of severe congenital myopathies: centronuclear myopathies linked to defect of muscle maturation and organelle positioning, and tubular aggregate myopathies linked to calcium handling defects.
The PhD project aims to identify the pathological mechanisms leading to these myopathies through molecular, cellular and in vivo approaches. For the cellular approaches we will use in vitro differentiation of cultured myofibers, genome editing and several modes of imaging (timelapse, super-resolution, confocal). To tackle the physiopathology, we will use zebrafish and mice models and modulate the level of the implicated genes by transgenesis (CRISPR/Cas9) and viral transduction (AAV).
The success of this project will expand our understanding of muscle maturation under normal and pathological conditions and potentially identify new therapeutic targets for myopathies.
Date limite de candidature : 1 novembre 2018