Dissecting MLIP role in the molecular cascade triggered by lamina dysfunction in Emery Dreifuss Muscular Dystrophy

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2021

Emery Dreifuss Muscular Dystrophy (EDMD) is a rare genetic disease causing skeletal and cardiac muscles dysfunction. Multiple gene mutations have been described in patients, all of them involving some protein connected to the structure or function of the nuclear lamina. The nuclear lamina is important for controlling the DNA three-dimensional structure, a key player in the regulation of genome functionality: i.e., how different portions of the genome are turned on or off in different cell types and tissues. However, to date, despite the identification of genes responsible for EDMD it is difficult to create a clear connection between genotype (specific mutations on the DNA sequence) and the molecular mechanisms underlying the phenotypes (disease symptoms). In other words, very little is known on the molecules involved in the cascade going from lamina dysfunction to the disease phenotypes. Moreover, until now, we have not been able to get a clear picture regarding the chromatin alterations because of the lack of adequate technologies to perform analyses in depth. MLIP is a gene with function unknown but potentially involved in the lamina disruption cascade based on the few known information so far. We will use advanced experimental techniques, including methods that we developed, to understand the role of MLIP in EDMD dystrophy. This study will not only improve our basic knowledge of the disease but can lead to the identification of new targets for innovative therapies.