Nancy BoniniUniversity of Pennsylvania
Nancy Bonini is the Florence R.C. Murray Professor of Biology at the University of Pennsylvania and a Howard Hughes Medical Institute Investigator. Her laboratory focuses on using Drosophila melanogaster as a tool to define genes important for human brain disease. A class of human neurodegenerative diseases involves expansion of a polyglutamine repeat within the various disease proteins. This polyglutamine expansion results in a dominant, toxic property of the disease protein, leading to neural degeneration. Huntington’s disease is of this class. We have recreated this class of human neurodegenerative disease in Drosophila by expressing in flies one of these human disease proteins with an expanded polyglutamine run. Whereas expression of the protein with a normal polyglutamine repeat has no effect, expression of the protein with an expanded polyglutamine repeat results in late onset, progressive degeneration in the nervous system. This indicates that the molecular mechanisms of human polyglutamine disease are conserved in Drosophila. Hence, we are now using Drosophila to define genes involved in the mechanisms and progression of polyglutamine disease, to identify suppressor mutations that can prevent or delay brain degeneration, and to extend these studies to additional diseases, like Parkinson’s disease and other motor neuron diseases. The Bonini lab is also expanding into neural injury and aging models in Drosophila by analyzing the nervous system with age. They hope that these studies will lead to insight into neural decline with aging, providing an approach for new treatments.