Severe hyperthermia can be lethal; however, lesser hyperthermic shock can protect against this lethality. Hyperthermic shock can cause the reversible arrest of growth and development. At the molecular level, hyperthermic shock induces the synthesis of """"""""heat shock proteins"""""""" (hsps). We believe the hsps mediate the effects of protection from severe shock, and of reversible growth arrest. The mechanisms may be related to those of viral carcinogenesis, which has been shown to interrelate with certain hsps. We propose to dissect the hsp induction system of Drosophila, in an effort to learn what aspects of cellular metabolism are critical to, and affected by, the hsp induction system. In vitro induction of hsp gene transcription (polytene chromosome puffing) will form a functional assay for several aspects of the response. We will isolate and characterize hsp84, the hsp most likely involved in mediating the cytoplasmic aspects of the hyperthermic response. We will perform a detailed genetic analysis of hsp84 to determine its role in vivo, and begin genetic analyses of other aspects of the response. We hope to gain an understanding of how cytoplasmic metabolism integrates with transcriptional control, and how, through hsp production, growth and development can be controlled.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM026693-06
Application #
3274081
Study Section
Genetics Study Section (GEN)
Project Start
1979-08-01
Project End
1985-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Indiana University Bloomington
Department
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47402
Torres, F A; Bonner, J J (1995) Genetic identification of the site of DNA contact in the yeast heat shock transcription factor. Mol Cell Biol 15:5063-70
Bonner, J J; Ballou, C; Fackenthal, D L (1994) Interactions between DNA-bound trimers of the yeast heat shock factor. Mol Cell Biol 14:501-8
Bonner, J J; Heyward, S; Fackenthal, D L (1992) Temperature-dependent regulation of a heterologous transcriptional activation domain fused to yeast heat shock transcription factor. Mol Cell Biol 12:1021-30
Wohlwill, A D; Bonner, J J (1991) Genetic analysis of chromosome region 63 of Drosophila melanogaster. Genetics 128:763-75
Bonner, J J (1991) Vectors for the expression and analysis of DNA-binding proteins in yeast. Gene 104:113-8
Leicht, B G; Bonner, J J (1988) Genetic analysis of chromosomal region 67A-D of Drosophila melanogaster. Genetics 119:579-93
Parker-Thornburg, J; Bonner, J J (1987) Mutations that induce the heat shock response of Drosophila. Cell 51:763-72
Sirotkin, K; Bartley, N; Perry 3rd, W L et al. (1986) Deletion polymorphism in a Drosophila melanogaster heat shock gene. Mol Gen Genet 204:266-72
Leicht, B G; Biessmann, H; Palter, K B et al. (1986) Small heat shock proteins of Drosophila associate with the cytoskeleton. Proc Natl Acad Sci U S A 83:90-4
Mortin, M A; Perrimon, N; Bonner, J J (1985) Clonal analysis of two mutations in the large subunit of RNA polymerase II of Drosophila. Mol Gen Genet 199:421-6