I developed the research for my Doctorate in the area of Human Genetics, with the study of a neurodegenerative disorder, Machado-Joseph disease(MJD)/Spinocerebellar ataxia type 3 (SCA3), particularly prevalent in the Azores Islands. I have invested in the historical genetics and epidemiology of the disease in the Azores, and was particularly interested in understanding how a seemingly simple monogenic disease could be so complex in its clinical and genetic manifestations. This interrogation was the starting point from which molecular-oriented research on MJD has emerged. The extensively studied Azorean pedigrees and the existence of a homogeneous cohort which has been thoroughly followed for several years have allowed the development of studies on several aspects of this disease, which have been developed under my coordination. My research group has focused on molecular mechanisms of MJD (such as alternative splicing), patterns of transmission, particular clinical presentations, genetic modifiers and molecular biomarkers. In the last four years we have been integrated the European ESMI Consortium, which has been establish to organize a large trial ready cohort of MJD patients. The high prevalence of MJD in the Azores supports a close collaboration between researchers and patients, namely through the ¿Associação Atlântica de Apoio ao doente de Machado-Joseph¿ a patient¿s organization that has been playing a fundamental role in the Azores.