Alcoholism is a common disease, affecting 4-5% of the population (reviewed by Zernig et al., 1997). In 1990, the cost of alcoholism and alcohol abuse to U.S. society was estimated at $136 billion (reviewed by Diamond, 1992). Despite these facts, our understanding of how alcohol affects behavior and brain function is incomplete. This proposal describes the identification of a mutation (EP1455) in a Drosophila MAPKKK gene, which causes an altered behavioral response to ethanol, cocaine, and nicotine. MAPK signaling is altered upon exposure to chronic ethanol in both rats and human hepatocyte cell culture (Chen et al., 1998; Kishore et al., 2002; Nelson et al., 2003), indicating that MAPK pathways are likely important targets for ethanol's effects on the brain. The goal of this project is to use EP1455 and the abundant genetic tools available in Drosophila to investigate the role of MAPK signaling in the response to ethanol.
The specific aims of this proposal are: ? 1. Determine the spatial and temporal requirements for the MAPKKK encoded by CG14217. ? 2. Characterize the functions of the kinase and PERM domains in the function of CG14217. ? 3. Investigate the function of MAP kinase signaling in drug response. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AA015000-01A1
Application #
6883032
Study Section
Special Emphasis Panel (ZAA1-EE (20))
Program Officer
Sorensen, Roger
Project Start
2005-03-01
Project End
2008-02-29
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
1
Fiscal Year
2004
Total Cost
$42,976
Indirect Cost
Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
French, Rachael L; Heberlein, Ulrike (2009) Glycogen synthase kinase-3/Shaggy mediates ethanol-induced excitotoxic cell death of Drosophila olfactory neurons. Proc Natl Acad Sci U S A 106:20924-9