Nancy Bonini, Ph. D. Professor of Biology Investigator of the Howard Hughes Medical Institute 306 Leidy Laboratories Department of Biology University of Pennsylvania Philadelphia, PA 19104 USA V +1 215 573.9267 F +1 215 898.8780 E nbonini@sas.upenn.edu

Nancy Bonini    (TIFF, ~2 MB)

research : publications : awards : affiliations : education : teaching

role of the eyes absent gene in eye formation; transgenic models for human neurodegenerative disease

The laboratory focuses on using Drosophila melanogaster to define genes important for survival of eye cells and for maintenance of the brain. In eye formation, we study the role of the eyes absent (eya) gene in eye formation. eya is a novel gene that is highly conserved to vertebrates. Loss of eya function in flies results in loss of the entire eye, whereas ectopic expression of eya directs ectopic eye formation. Moreover, eya in combination with a number of other genes of eye formation (sine oculis, eyeless, dachshund) synergizes with eya in eye formation, suggesting that eya is a critical, rate limiting step of eye development. We are using various genetic, molecular, and cell biological approaches to define in greater detail functional domains of the eya gene, and its molecular role in eye formation.

A second project involves using Drosophila 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 result 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 in order to define genes involved in the mechanisms and progression of polyglutamine disease, and to identify suppressor mutations that can prevent or delay brain degeneration.

selected publications Auluck P.K., and Bonini N.M. 2002. Pharmacological prevention of Parkinson disease in Drosophila. Nat Med 8:1185-6. Auluck P.K., Chan H.Y., Trojanowski J.Q., Lee V.M., and Bonini N.M. 2002. Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295:865-8. Bonini N.M. 2002. Chaperoning brain degeneration. Proc Natl Acad Sci U S A 99 Suppl 4:16407-11. Chan H.Y., Warrick J.M., Andriola I., Merry D., and Bonini N.M. 2002. Genetic modulation of polyglutamine toxicity by protein conjugation pathways in Drosophila. Hum Mol Genet 11:2895-904. Chan H.Y., Warrick J.M., Gray-Board G.L., Paulson H.L., and Bonini N.M. 2000. Mechanisms of chaperone suppression of polyglutamine disease: selectivity, synergy and modulation of protein solubility in Drosophila. Hum Mol Genet 9: 2811-20. Fortini M.E. and and N.M. Bonini 1999. Modeling human neurodegenerative diseases in Drosophila: on a wing and a prayer. Trends in Genetics 16:161-167. Warrick J., Chan H.Y.E., Chai Y., Paulson H. and N.M. Bonini 1999. Suppression of polyglutamine disease in Drosophila by the molecular chaperone hsp70. Nature Genetics 23:425-428. Warrick J.M., Paulson H., Gray-Board G.L., Bui Q.T., Fischbeck K., Pittman R.N., and N.M. Bonini 1998. Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila. Cell 93:939-949. Warrick J.M., Paulson H., Gray-Board G.L., Bui Q.T., Fischbeck K., Pittman R.N., and N.M. Bonini 1998. Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila. Cell 93: 939-949. Bonini N.M., Bui Q.T., Gray-Board G.L. and J.M. Warrick 1997. The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates. Development 124: 4819-4826. Zimmerman J., Bui Q., Steingrimmson E., Nagle D.L., Fu W., Genin A., Spinner N., Copeland N.G. Jenkins N.A., Bucan M., and N.M. Bonini 1997. Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene. Genome Research 7:128-141. Bonini N.M. 1997. Surviving Drosophila eye development. Cell Death & Differentiation 4:4-11.

awards David and Lucile Packard Fellowship for Science and Engineering Basil O'Connor Award, March of Dimes John Merck Scholars Award in the Biology of Developmental Disabilities in Children

professional affiliations Society for Neuroscience American Society for Cell Biology Genetics Society of America

education Ph.D., University of Wisconsin-Madison, Neuroscience, 1987 A.B., Princeton University, Biology, 1981

teaching BIOL 221: Molecular Biology and Genetics COLL 100: How Do You Know?