Understanding the link between the shape of nuclei and DNA organisation in muscle cells from people living with laminopathy  

The LMNA gene makes proteins called lamin A/C. Genetic changes to LMNA cause conditions called laminopathies, which affect a variety of organs, particularly the heart and the muscles. Each cell has a nucleus, a round-shaped structure in which DNA is stored. Lamin A/C proteins form a structure called the nuclear lamina, which is critical to maintaining the structure of the cell nucleus.  

DNA inside the nucleus is not randomly distributed but is organised in a careful manner, with help of the nuclear lamina. One of the cellular features most associated with laminopathies is changed nuclear shape. This occurs in muscle cells when there is a problem with lamin proteins, because muscles are a part of the body that moves frequently, meaning a lot of force and physical stress is placed on the muscle cells.  

Professor Tedesco and his team have developed a model of muscles under laboratory conditions. These are called mini-muscles – read more here. In this new study, the team will isolate nuclei of particular shapes from mini-muscles made from cells taken from people who live with laminopathies. They will use methods for ‘reading’ the genes, broadly called sequencing, to see if changes in nuclear shape have any effect on the organisation of DNA.  

As well as isolating nuclei of different shapes from laminopathy cells and checking if changes in shape correlate with changes in DNA organisation, the team will also test if muscle contractions have an impact on DNA organisation. Further on, the aim will be to find any potential treatments that can increase muscle function through improving DNA organisation.

This research will increase our understanding of the causes of laminopathies. These findings might help Professor Tedesco and his team design and develop new treatments to manage the condition.