Model organisms and rare diseases

The main interest of our laboratory has been the development of models to study the genetic bases and the pathophysiology of inherited neurometabolic disorders.

Since the introduction of next generation sequencing technologies, interpretation of genomic variants, their validation and predictions of possible effects on gene products have acquired a crucial importance and become one of the most relevant challenges in human genetics. What we have been mostly interested in is the setting up of simple models that allow to validate novel variants identified in patients affected by rare genetic diseases, but also to establish genotype-phenotype correlations and to analyze the molecular pathogenesis of these conditions. In this regard, we have successfully employed S. cerevisiae to analyze missense mutations in genes affecting fundamental cellular processes or mammalian cells in order to test the effects of genomic variants on transcript maturation.

More recently, we have moved to multicellular models, including C. elegans and D. rerio. These organisms represent simple highly prolific organisms with a rapid life cycle that display organized tissues and organs and allow studying the effects of novel variants on nervous system development.
Our interest is now moving to cancer genetics, and particularly to the study of the mechanisms driving pediatric cancers associated with a genetic predisposition. We are employing the same organisms to model germline mutations in oncosuppressors/oncogenes identified in rare tumor predisposing syndromes in order to deeply analyze cancerogenesis and to set up simple models for drug screening.