FUNCTIONAL KNOCK-OUT AND CHARACTERIZATION OF DROSOPHILA GENES HOMOLOGOUS TO A SELECTED SUBSET OF HUMAN MUSCLE GENES

This research project entails the study of a selected set of genes, which are mainly active in human skeletal muscle, and for which there is a lack of information concerning the function or the possible involvement of alterations in such genes in neuromuscular pathology. The genes object of this study were selected, using a bioinformatic approach, from a database consisting of the sequences of more than 5,000 genes isolated from human skeletal muscle by the Muscle Research Group of the Biotechnology Center (CRIBI ) of the University of Padova. Clearly, it is not possible to study the effects of experimentally induced alterations in these genes directly in humans. Consequently, it is necessary to adopt 'model' organisms, which are amenable to experimental approaches of this kind, allowing the conduction of such studies in an efficient and ethically acceptable manner. We plan to infer the effects caused by the disruption of each of the selected genes on neuromuscular function, through the analysis of the corresponding disrupted fruit fly genes. The fruit fly (Drosophila melanogaster) is a model organism of paramount importance in Genetic and Biomolecular Research and for which, as in the case of man, the complete genomic sequence has recently become available. Despite the apparent unlikeness, man and the fruit fly share a wealth of genetic similarities (homologous genes) which determine remarkable similitudes between the two organisms at the biochemical and metabolic level. Through the use of highly efficient and sophisticated techniques it is possible, relatively rapidly, to specifically disrupt single fly-genes and to evaluate the effects of such alterations on the structural and functional characteristics of the insect's muscles. This approach should allow the identification of those genes, among the set selected for analysis, which could potentially be involved in the causation of genetically determined neuromuscular diseases with an as yet unknown basis.