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Exploring the role of post-translational hydroxylation in transcriptional control: in vitro and in vivo studies on hypoxia inducible factor asparaginyl hydroxylase (FIH)

Reference	BBS/B/07683
Principal Investigator / Supervisor	Professor Christopher Joseph Schofield
Co-Investigators / Co-Supervisors	Professor Sir Peter Ratcliffe
Institution	University of Oxford
Department	Oxford Chemistry
Funding type	Research
Value (£)	213,032
Status	Completed
Type	Research Grant
Start date	01/08/2004
End date	31/07/2007
Duration	36 months

Abstract

Sensing of oxygen levels and appropriate feedback mechanisms are essential for all aerobic organisms. We have identified a family of hydroxylases that modulate the activity of hypoxia inducible factor (HIF), a protein which mediates transcription of the array of genes involved in the hypoxic response. The main objective of this work is to pioneer and utilise methodology to assess the importance of individual hydroxylases by correlating the in vitro oxygen binding properties of a specific HIF hydroxylase (factor inhibiting HIF, FIH) with its in vivo role as an oxygen sensor. Phase I of the project will comprise generation and kinetic/structural analysis of FIH mutants with altered oxygen-binding properties. Phase II will comprise the introduction of mutants into cell lines deficient in FIH and comparison of the hypoxic response of the mutant cell lines with those containing wild-type FIH.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	X – not assigned to a current Research Topic
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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