TRANSCRIPTIONAL CONTROL OF DROSOPHILA HEART DEVELOPMENT AS A MODEL SYSTEM TO INVESTIGATE THE MOLECULAR MECHANISMS UNDERLYING INBORN HUMAN HEART DISEASES

Our research focuses on the use of the fruit fly (Drosophila ) as a model system to study the molecular properties of genes involved in inborn heart diseases. According to the available data, these syndromes are the cause of death in about 1 out of 100 live-born babies and 1 in 10 stillborns. In addition, they are a source of high medical expenses due to complex surgical interventions. We plan to investigate the molecular functions of genes involved in cardiac development in Drosophila in order to extrapolate this information for the corresponding human genes and their involvement in human cardiac diseases.nbsp;nbsp;nbsp;nbsp; The Drosophila genome has been entirely sequenced and it is twenty times smaller than the human one. This comprehensive genetic information and the exceptional rapidity of development of this organism mean that Drosophila is ideal for undertaking genetic manipulations in a rapid and focused manner. Moreover, human genes introduced into Drosophila are able to rescue most of the phenotypes caused by mutations in the corresponding fly genes. These data reveal the conservation of genetic functions between these evolutionarily distant organisms and validate the proposed use of Drosophila to study human disease.nbsp;nbsp;nbsp;nbsp; The genes that we will deal with encode proteins (transcription factors) that regulate expression of downstream target genes responsible for the morphogenesis and the physiology of the heart. We plan to identify the regulatory sequences of the target genes and then use them to understand how gene mutations can affect heart development and lead to congenital heart diseases. The knowledge acquired will also allow the development of useful preventive therapies, as Drosophila can be employed both to test pharmacological cures and to develop gene therapies based on stem cells.