The long term objective of this research is to learn how the target- derived neurotrophins transmit information through axons. In preliminary studies, my post-doctoral mentors, have shown that neurotrophin receptor proteins (Trks) play a pivotal role in retrograde signaling through rat sciatic nerve axons.
The specific aim of my research is to determine how information is conveyed by Trks (or upon Trks) through the axon. As described in the study plan, I will be working on compartmental cultures (Campenot cultures) of dorsal root ganglion neurons. I will install molecular tags on the ligand binding domain of Trk receptor protein expressed at the nerve ending. I will install molecular tags on the ligand binding domain of Trk receptor protein exposed at the nerve ending. I will determine whether the tagged Trk protein moves through the axon at the same rate as the retrograde signal. To go beyond the descriptive level, I will construct adenovirus expression vectors containing dominant negative mutations of dynamin. I will use these expression vectors to define the role of vesicular transport in retrograde signaling. These studies have practical implications for treatment of human peripheral neuropathies (secondary to diabetes or toxins), neurodegenerative diseases including amyotrophic lateral sclerosis and Alzheimer's, and spinal cord injuries. All these disease processes involve the death of neurons that have long projects and whose survival is regulated by neurotrophins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS010662-02
Application #
6140498
Study Section
Special Emphasis Panel (ZRG1-NLS-1 (01))
Program Officer
Leblanc, Gabrielle G
Project Start
1998-08-01
Project End
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215