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Oxidation states of Calmodulin-kinase II: its role in heart disease

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  • Full or part time
    Prof J Colyer
  • Application Deadline
    No more applications being accepted
  • Awaiting Funding Decision/Possible External Funding
    Awaiting Funding Decision/Possible External Funding

Project Description

Calmodulin-dependent kinase II (CaMKII) is an enzyme present in the contractile cells of the heart which
coordinates the structure and contractile performance of the myocardium. Excessive activation of CaMKII however, drives new processes in the heart (hypertrophy, inflammation) which injure the myocardium or cause death through cardiac arrhythmia.

A new mechanism of CaMKII activation based upon the oxidation of specific residues in the protein has been described (Erickson et al. (2008) Cell 133, 462-474). Two methionine residues (M281,M282) in the regulatory domain of the enzyme are oxidised in cells stressed by a variety of pathological insults. These modifications create a long lived active enzyme which drives pathological adaptations in heart structure and function, and contributes significantly to cell death. As such this
modification appears central to major forms of heart disease (heart failure, arrhythmias/sudden cardiac death).

Professor John Colyer (Biological Sciences) and Dr Stuart Warriner (Chemistry) wish to identify an outstanding candidate to nominate for a fellowship to fund their Ph.D. research in this area of chemical biology & medicine.
An application will be made with the selected candidate to the British Heart Foundation for a research project which seeks to:
 Define the chemical oxidation states of CaMKII;
 Create chemical and biochemical probes able to monitor CaMKII oxidation in
biological specimens; and
 Define the role of (cardiac) CaMKII oxidation in health & diseased states.

Funding Notes

Applicants should send a full curriculum vitae and letter outlining their case for support to [Email Address Removed] by July 29, 2011. A selection process involving an interview will be conducted in August 2011, and an application for Ph.D. fellowship will be submitted to BHF in Sept 2011. A decision from BHF would be expected in Mar 2012 and Ph.D. to start within the following 6 months.

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