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Molecular basis of NADPH oxidase activation

Reference	BBS/E/B/0000C235
Principal Investigator / Supervisor	Dr Phillip Hawkins
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	438,693
Status	Completed
Type	Institute Project
Start date	01/11/2008
End date	31/03/2012
Duration	41 months

Abstract

Neutrophils and macrophages are types of white blood cell and are key components of the innate immune system. These cells are professional phagocytes and rapidly engulf and destroy microbes. One of the early events in this process is production of superoxide (02) by activated NADPH oxidase. Hereditary mutations in the NADPH oxidase complex in individuals with chronic granulomatous disease result in recurring life-threatening infections, underlining the importance of this enzyme. However, because of the potential tissue damage that can also be caused by the reactive oxygen species produced by NADPH oxidase, it is tightly regulated. Too much NADPH oxidase activity can be harmful. When neutrophil recruitment and activation by the immune system is abnormally high, life-threatening acute inflammatory tissue injury can result. This is especially prevalent in certain acute viral and bacterial lung infections. The core catalytic machinery of the enzyme requires the association of four regulatory protein subunits to become fully active. The molecular organisation of the active NADPH oxidase has been the subject of many investigations, however, much remains unexplained about how signalling pathways activate NADPH oxidase. The goal of this research is to understand the structural basis of NADPH oxidase activation and to develop specific chemical inhibitors of this process.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	Immunology, Structural Biology
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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