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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Genetics Study Section (GEN)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Chicago
Schools of Medicine
United States
Zip Code
Kayatekin, Can; Amasino, Audra; Gaglia, Giorgio et al. (2018) Translocon Declogger Ste24 Protects against IAPP Oligomer-Induced Proteotoxicity. Cell 173:62-73.e9
Frederick, Kendra K; Michaelis, Vladimir K; Caporini, Marc A et al. (2017) Combining DNP NMR with segmental and specific labeling to study a yeast prion protein strain that is not parallel in-register. Proc Natl Acad Sci U S A 114:3642-3647
Frederick, Kendra K; Michaelis, Vladimir K; Corzilius, Björn et al. (2015) Sensitivity-enhanced NMR reveals alterations in protein structure by cellular milieus. Cell 163:620-8
Reymer, Anna; Frederick, Kendra K; Rocha, Sandra et al. (2014) Orientation of aromatic residues in amyloid cores: structural insights into prion fiber diversity. Proc Natl Acad Sci U S A 111:17158-63
Frederick, Kendra K; Debelouchina, Galia T; Kayatekin, Can et al. (2014) Distinct prion strains are defined by amyloid core structure and chaperone binding site dynamics. Chem Biol 21:295-305
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
Lancaster, Alex K; Nutter-Upham, Andrew; Lindquist, Susan et al. (2014) PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition. Bioinformatics 30:2501-2
Halfmann, Randal; Wright, Jessica R; Alberti, Simon et al. (2012) Prion formation by a yeast GLFG nucleoporin. Prion 6:391-9
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

Showing the most recent 10 out of 61 publications