This is an application for renewal of an NIH Research Career Award (RCA). The primary purpose of the application is to reduce the applicant's teaching load to a level that will allow him to pursue ongoing research on the genetic basis of alcohol action. A typical teaching load in the Department of Psychology is four full-semester courses per year. The only exceptions are faculty who have career research awards. I have initiated a study wherein we are identifying and mapping mouse genes of relevance to alcoholism using the Long-Sleep (LS) and Short-Sleep (SS) lines of mice that were selectively bred for differential sensitivity to the anesthetizing action of alcohol. We have localized major QTLs for this trait are are closing on the genes underlying the phenotype using congenic strain analysis. During the tenure of this award I will pursue research in the biological and molecular basis of alcohol action both in this model as well as the DBA/2 by C57BL/6 mouse model for alcohol preference/avoidance. I am currently in the third year of a 4-year R01 to map genes leading to neurosensitivity to ethanol and have an application pending to identify new QTLs for a variety of traits using a series of 110 RIs from the ILS by ISS strains. The RSDA will also provide the opportunity for increased interactions with personnel in the Department of Pharmacology at the University of Colorado Health Sciences Center (UCHSC) which includes Drs. Richard Deitrich, and James Sikela and members of their respective laboratories as well as Dr. Gene Erwin in the School of Pharmacy also at the UCHSC. Active collaborations are already underway with Drs. Deitrich, Erwin, Adron Harris (now at U. Texas) and Sikela. I will continue to develop my expertise in DNA sequencing and bioinformatics and to learn microarray methodologies to test the hypothesis that particular genes are involved in alcohol action. Additional educational experience will be obtained by regular attendance of the annual meeting of the Research Society on Alcoholism (RSA), the biannual meeting of the Gordon Conference on QTL Mapping as well as specialized meetings on the molecular genetic basis of alcohol action, as these conferences should arise. I will continue to develop my knowledge of QTL mapping by discussions and interactions with colleagues both at CU and elsewhere who are expert both in the molecular basis of gene detection and analysis.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Scientist Development Award - Research (K02)
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Health Services Research Review Subcommittee (AA)
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Lucas, Diane
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University of Colorado at Boulder
Other Domestic Higher Education
United States
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Henderson, Samuel T; Bonafe, Massimiliano; Johnson, Thomas E (2006) daf-16 protects the nematode Caenorhabditis elegans during food deprivation. J Gerontol A Biol Sci Med Sci 61:444-60
Johnson, Thomas E (2005) Genes, phenes, and dreams of immortality: the 2003 Kleemeier Award lecture. J Gerontol A Biol Sci Med Sci 60:680-7
Proctor, William R; Wu, Peter H; Bennett, Beth et al. (2004) Differential effects of ethanol on gamma-aminobutyric acid-A receptor-mediated synaptic currents in congenic strains of inbred long and short-sleep mice. Alcohol Clin Exp Res 28:1277-83
de Castro, Edouard; Hegi de Castro, Sarah; Johnson, Thomas E (2004) Isolation of long-lived mutants in Caenorhabditis elegans using selection for resistance to juglone. Free Radic Biol Med 37:139-45
Downing, Chris; Shen, Elaine H; Simpson, Victoria J et al. (2003) Mapping quantitative trait loci mediating sensitivity to etomidate. Mamm Genome 14:367-75
Cypser, James R; Johnson, Thomas E (2003) Hormesis in Caenorhabditis elegans dauer-defective mutants. Biogerontology 4:203-14
Rikke, Brad A; Yerg 3rd, John E; Battaglia, Matthew E et al. (2003) Strain variation in the response of body temperature to dietary restriction. Mech Ageing Dev 124:663-78
Yashin, Anatoli I; Cypser, James W; Johnson, Thomas E et al. (2002) Heat shock changes the heterogeneity distribution in populations of Caenorhabditis elegans: does it tell us anything about the biological mechanism of stress response? J Gerontol A Biol Sci Med Sci 57:B83-92
Bennett, Beth; Beeson, Mary; Gordon, Lena et al. (2002) Genetic dissection of quantitative trait loci specifying sedative/hypnotic sensitivity to ethanol: mapping with interval-specific congenic recombinant lines. Alcohol Clin Exp Res 26:1615-24
Eisenman, Leonard M; Donovan, H Scott; Johnson, Thomas E (2002) Alcohol differentially affects c-Fos expression in the supraoptic nucleus of long-sleep and short-sleep mice. Brain Res 935:114-7

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