Nancy M. Bonini
Philadelphia, PA 19104-6018
Fax: (215) 573-5754
Lab: (215) 898-9028
Princeton University, 1981.
University of Wisconsin-Madison, 1987.
Description of Research ExpertiseKEY WORDS:
Neurodegeneration; suppressor mechanisms; human disease; Alzheimer's, Parkinson's and Huntington's diseases; Amyotrophic Lateral Sclerosis and Frontotemporal Dementia; Ageing; microRNAs; RNA binding proteins; stress response
Molecular genetics of neurodegenerative disease.
Genetics, molecular biology, cell biology
Our laboratory focuses on using the powerful genetics of Drosophila melanogaster in order to define genes that are critical to prevent human brain degeneration. Many human neurodegenerative diseases are poorly understood and untreatable, including Huntington's, Parkinson's and Alzheimer's diseases. In order to pioneer new ways to prevent and treat these devastating diseases, we are applying the power of Drosophila genetics to the problem. Overall, genes in Drosophila are highly conserved to humans, such that any genes that we find which are critical to maintenance of the brain in flies are likely to have conserved homologues in humans - with conservation not only of protein sequence, but also of protein function.
Toward this end, we have introduced human disease genes into Drosophila in order to recreate the respective human disease in flies. One example is human polyglutamine disease, of which Huntington's disease is an example. Expression of a mutant human polyglutamine disease gene in flies confers a phenotype remarkably reflective of the human disease -- late-onset, progressive neural degeneration. With this fly model, we are using molecular and genetic approaches in order to define genes and mechanisms involved in progression of degeneration, and ways to stop the degeneration entirely. One powerful class of suppressor genes we have defined include the molecular chaperones, which alter protein folding, potentially masking and diminishing disease protein toxicity. We are generating fly models for additional human neurodegenerative diseases, and continuing with Drosophila genetic approaches to identify and study suppressor mechanisms for preventing neural degeneration. By this approach, we are using the powerful genetics of Drosophila in order to pioneer new approaches to understand and prevent human neurodegenerative disease.
Selected PublicationsAuluck P.K., and Bonini N.M. : Pharmacological prevention of Parkinson disease in Drosophila. Nat Med 8: 1185-6, 2002.
Auluck P.K., Chan H.Y., Trojanowski J.Q., Lee V.M., and Bonini N.M. : Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295: 865-8, 2002.
Bonini N.M.: Chaperoning brain degeneration. Proc Natl Acad Sci USA 99(Suppl 4): 16407-11, 2002.
Chan H.Y., Warrick J.M., Andriola I., Merry D., and Bonini N.M. : Genetic modulation of polyglutamine toxicity by protein conjugation pathways in Drosophila. Hum Mol Genet 11: 2895-904, 2002.
Chan H.Y., Warrick J.M., Gray-Board G.L., Paulson H.L., and Bonini N.M. : Mechanisms of chaperone suppression of polyglutamine disease: selectivity, synergy and modulation of protein solubility in Drosophila. Hum Mol Genet 9: 2811-20, 2000.
Fortini M.E. and and N.M. Bonini : Modeling human neurodegenerative diseases in Drosophila: on a wing and a prayer. Trends in Genetics 16: 161-67, 1999.