Flagship projects

Muscles and forces: the secret dialogue between movement and DNA

CONOCY: understanding how mechanical forces directly influence muscle function

CONOCY investigates how the mechanical forces generated by muscle movement are transmitted to the nucleus of muscle cells, and how this internal communication breaks down in certain neuromuscular diseases.

Scientific challenge

Muscle is constantly subjected to physical stresses. These forces influence its organisation, its adaptation and its capacity to repair itself. Their transmission to the nucleus, via the cytoskeleton, can alter gene activity. When this mechanical dialogue is disrupted, muscle loses its ability to adapt, which may contribute to diseases such as muscular dystrophy or certain centronuclear myopathies.

Key questions to unravel

The team is working to establish how forces are conveyed to the nucleus, how cells sense these signals and how the connections between the nucleus and the cytoskeleton control gene expression. The aim is to identify the mechanisms that enable muscle to adapt to mechanical stress, and to understand why they fall short with ageing or in certain diseases.

Scientific and methodological approach

The researchers alter the mechanical stresses applied to muscle cells in culture in order to observe their effects on internal organisation and on the nucleus. They also study how cells align and organise themselves before forming muscle fibres, using dynamic imaging approaches. Finally, they analyse how abnormalities in nuclear envelope proteins disrupt these mechanisms in models of muscle diseases.

Understanding how muscle forms and maintains itself is crucial if we are to know what differs in diseased or ageing muscle, and to identify precise therapeutic targets, whether pharmacological or genetic. In the medium term, the challenge is to map the mechanisms and the players involved so that, in the long term, we can formulate therapeutic strategies to keep muscle healthy or to regenerate diseased muscle.
Bruno Cadot, researcher at the Institute of Myology and head of the imaging facility

Expected impact on research and clinical practice

CONOCY could reveal fundamental mechanisms that allow muscle to remain functional despite mechanical stress. This detailed understanding could pave the way for therapeutic strategies aimed at preserving muscle function or improving regeneration in disease or with age. The imaging tools developed as part of this project will also benefit neuromuscular research as a whole.