This proposal has 4 major objectives, all focused on the heat shock response: 1) When the cells or tissues of Drosophila melanogaster are exposed to elevated temperatures, they respond by inhibiting the synthesis of normal cellular proteins and inducing the synthesis of a small number of heat shock proteins. This transition represents the cleanest and most dramatic example of selective translation yet described. Using a mixture of heat shock and control cell messenger RNAs and an in vitro translation assay system, we will fractionate heat shock cells in an attempt to identify the factors involved in regulating this transition. 2) We wish to investigate the changing RNA metabolism in yeast cells during heat shock. Using standard pulse labeling and nucleic acid hybridization techniques, we hope to obtain an accurate picture of the balance between message synthesis and degradation. 3) We wish to obtain antibodies to heat shock proteins, and use them to investigate the intracellular location and function of these proteins in Drosophila and other eukaryotes through indirect immunofluorescence. 4) We have recently obtained evidence that heat shock proteins are transported to the nucleus by some special mechanism. We hope to elucidate the processes involved in this transport.
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| Kayatekin, Can; Matlack, Kent E S; Hesse, William R et al. (2014) Prion-like proteins sequester and suppress the toxicity of huntingtin exon 1. Proc Natl Acad Sci U S A 111:12085-90 |
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| Bryan Jr, Allen W; O'Donnell, Charles W; Menke, Matthew et al. (2012) STITCHER: Dynamic assembly of likely amyloid and prion ?-structures from secondary structure predictions. Proteins 80:410-20 |
| Krishnan, Rajaraman; Goodman, Jessica L; Mukhopadhyay, Samrat et al. (2012) Conserved features of intermediates in amyloid assembly determine their benign or toxic states. Proc Natl Acad Sci U S A 109:11172-7 |
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