- Neuronal injury, such as spinal cord damage, is devastating and typically leads to extreme reduction in life quality. Spinal cord injuries alone affect ~15,000 people/year in the US;about 10,000 of these patients will be permanently paralyzed and many others die due to their injuries. Few approaches are available to treat such devastating injuries, in large part because little is clear about biological pathways &genes that influence regeneration, due to the complexity of the process and the limited systems available for attacking the problem. New insight may be applicable not only to spinal cord injury, but also to brain trauma, stroke and neurodegenerative disease. We propose to develop one of the premier model organism systems-Drosophila-as a new experimental paradigm for adult-stage neural regeneration. In pilot studies in living adult animals, we have severed the wing nerve bundle with a laser and observed degeneration of the nerve tract. Striking preliminary observations show that after a 3-week quiescent period, the nerve bundle regenerates in about 40% of the animals. We will perform detailed characterization of this nerve injury experimental paradigm, including extent and speed of degeneration, as well as extent, speed and accuracy of regeneration. Then, using this system, we will exploit the available sets of molecularly-defined gene mutants in the fly to identify new genes &pathways. Because the baseline regeneration appears partial, this experimental paradigm will reveal both pathways that influence degeneration, as well as those that modulate regeneration. These studies will establish a new experimental paradigm for regeneration studies, and reveal new molecules &pathways, providing basic biological insight and the foundation for discovery of novel therapeutics for nerve injury, damage and degenerative disease.

Public Health Relevance

Statement: Neuronal injury, such as spinal cord damage, is devastating and typically leads to extreme reduction in life quality. In the US alone, spinal cord injuries affect ~15,000 people/year;about 10,000 of these patients will be permanently paralyzed and many others die due to their injuries. The studies proposed will establish and utilize one of the premier model organism systems-Drosophila-as a new experimental paradigm for basic biological insight and therapeutics in neural injury and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS066312-04
Application #
8322108
Study Section
Special Emphasis Panel (ZMH1-ERB-L (05))
Program Officer
Jakeman, Lyn B
Project Start
2009-09-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$293,044
Indirect Cost
$97,044
Name
University of Pennsylvania
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Soares, Lorena; Parisi, Michael; Bonini, Nancy M (2014) Axon injury and regeneration in the adult Drosophila. Sci Rep 4:6199
Fang, Yanshan; Soares, Lorena; Bonini, Nancy M (2013) Design and implementation of in vivo imaging of neural injury responses in the adult Drosophila wing. Nat Protoc 8:810-9
Fang, Yanshan; Soares, Lorena; Teng, Xiuyin et al. (2012) A novel Drosophila model of nerve injury reveals an essential role of Nmnat in maintaining axonal integrity. Curr Biol 22:590-5