Project Details


We propose to use the following approaches to explore the stress response
(heat shock response) in human cells: 1. Cloning of the genes and cDNAs.
These will be used (i) as tools for analyzing the mechanisms involved in
the response, (ii) for elucidation of (possibly common) regulatory regions
and effector molecule(s) which bind to them, and (iii) for genetic
manipulations and introduction into cells to determine whether different
inducers act by the same mechanisms. 2. Transcriptional control is of two
types, which we have described previously. Through experiments carried out
in vivo and in vitro we will dissect the mechanism further, in particular,
(i) to discover the nature of the regulation of transcription of the stress
response genes, (ii) to distinguish between various explanations for the
decreased production of normal mRNAs and non-coding RNAs, and (iii) to
develop cell-free systems as a means of identifying and purifying
regulatory components. 3. Translational control can occur at the levels of
initiation and elongation in different kinds of stress. We will explore
the mechanisms of these processes, and test specific models to explain the
unusual dependence of protein synthesis on continuous RNA sysnthesis.
Cell-free systems will be developed to allow fractionation and purification
of regulatory components responsible for the different types of control.
4. Cell mutants deficient in the responses to various inducing treatments
will be isolated to afford a genetic approach to the nature of the
Effective start/end date12/31/8912/31/89


  • National Institute of General Medical Sciences


  • Genetics
  • Molecular Biology


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