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The molecular responses and functional competence of cultured mammalian cells at sub-physiological temperatures: the cold-shock proteome

Reference	BB/C006569/1
Principal Investigator / Supervisor	Professor Christopher Smales
Co-Investigators / Co-Supervisors	Dr Martin Carden
Institution	University of Kent
Department	Sch of Biosciences
Funding type	Research
Value (£)	239,619
Status	Completed
Type	Research Grant
Start date	02/05/2005
End date	01/05/2008
Duration	36 months

Abstract

The response to elevated temperature has been extensively studied in both prokaryotic and eukaryotic systems and generally involves the induction of heat-shock proteins (HSPs), a ubiquitous family of proteins highly conserved from bacteria to plants and mammals. In contrast, the mechanisms by which cultured mammalian cells respond to sub-physiological temperatures have not been extensively investigated and so we are both poorly understood and open to wide conjecture. What is becoming clear is that exposing eukaryotic cells to sub-optimal temperatures invokes a coordinated response involving modulation of the cell cycle, metabolism, transcription, translation, chaperones, and the cell cytoskeleton. This programme will utilise an advanced proteomic analysis platform to characterise changes in functional gene expression and protein modification(s) implicated in the molecular response to, and recovery from, cold-shock in cultured mammalian cells. To achieve this we will undertake five related approaches. The first approach is targeted at the induction of proteins involved in the molecular response(s) governing cellular adaptation to sub-physiological temperatures (cold-shock) and is pertinent to understanding how these responses are co-ordinated. The second is to investigate the response of mammalian cells upon recovery from cold-shock. The third is targeted at recombinant protein production and the secretory pathway and is highly relevant to the engineering of eukaryotic cells for the production of therapeutic proteins in vitro. The fourth approach will be to target and investigate cold-shock and the cell cytoskeleton, and the relationship between the cell cytoskeleton, chaperones, translation, protein turnover and energy metabolism. The fifth will be to investigate proteins implicated in the response to changes in dissolved oxygen, both those involved in hyperoxic responses whereby an increase in reactive oxygen species would be expected, and those involved in hypoxicresponses. The outcome of this research will be (i) an understanding of the molecular response(s) governing cellular adaptation to cold-shock in cultured mammalian systems, (ii) elucidation of the effects on, and mechanisms that determine, heterologous protein production in mammalian cells and sub-physiological temperatures, and (iii) the identification of rational targets for novel gene expression and manipulation technologies.

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	Industrial Biotechnology, Pharmaceuticals
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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