Biopark - Bâtiment A 8, rue de la Croix-Jarry
The team of Gisèle Bonne is part of the Research Center in Myology created on January 1st 2014 on the site of La Pitié-Salpétrière university hospital and currently directed by Prof. Bertrand Fontaine. The Research Center in Myology is a center of excellence for multidisciplinary research on the muscle and its pathologies. It gathers over one hundred persons, researchers, doctors, engineers and technicians from INSERM, Sorbonne University, CNRS and Association Institut de Myologie.
The research topics of the G Bonne team focus on 2 groups of neuromuscular disorders (NMD): myopathies due to defects of the Myomatrix [collagen type VI & ECM-related disorders (Allamand et al. 2011, Skelet Muscle); V Allamand’s group] and of the Myonucleus [Emery-Dreifuss muscular dystrophies (EDMD) & other striated muscle laminopathies (SML) due to mutations of the LMNA gene encoding A-type lamins or genes encoding related nuclear envelope components (Bertrand et al. 2011, Biochem Soc Trans.; Azibani et al. 2014, Semin Cell Dev Biol); Group G Bonne/ AT Bertrand]. These myopathies with prominent contractures or ‘contractural myopathies’ share some clinical features, and may be differentially diagnosed.
These diseases are highly heterogeneous, both clinically and genetically, and no treatment is available yet. Our previous activities have led to the identification of genetic defects, the development of tools (cellular and animal models) and the deciphering of pathophysiological clues for a better comprehension of the molecular bases and the identification of therapeutic targets. Many unresolved issues remain: 1) absence of molecular diagnosis for a subset of patients, 2) precise function of implicated proteins and underlying pathophysiological mechanisms… Several common points (contractile dysfunction, mechanobiology defects, fibrosis…) have been and are still being addressed transversally through pooling of our specific expertise (nuclear envelop, nucleoplasm, extracellular matrix…).
The team’s project revolves around 3 axes:
1) defining the genetic and clinical spectrum and the natural history of these NMDs;
2) investigating the pathophysiological mechanisms of gene mutations that induce these cardiac and/or skeletal muscle affections with the overall goal
3) to identify and test therapeutic avenues for these disorders. This is carried out on biological material from patients (DNA, RNA, cultured cells and biopsies) as well as various animal models we have developed.
25–30 May 2020, Spetses Island, Greece