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BBSRC CASE Studentship: Nitric oxide and calcium signalling

Reference	BBS/E/B/0000Q101
Principal Investigator / Supervisor	Dr Martin Bootman
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	11,132
Status	Completed
Type	Institute Project
Start date	01/10/2003
End date	30/09/2006
Duration	36 months

Abstract

Many of the effects of nitric oxide (NO) are mediated by changes in cellular calcium homeostasis, either directly through nitrosylation of proteins or through cGMP/PKG-dependent processes. It is well known that the production of nitric oxide requires an increase in intracellular calcium, which forms a complex with calmodulin to then stimulate NOS to generate NO. Less is known, however, about the importance of the feedback NO has on further intracellular calcium signals. In endothelia, NO has been shown to both increase and decrease calcium entry, mobilization and extrusion. Similarly, in cardiac muscle NO has been shown to have both positive and negative inotropic effects. The disparity of results is most likely due to differences between experimental models, cell lines and various NO donors selected by investigators. In general, there is a lack of systematic studies looking at the effect of NO on cellular calcium. This project proposes to undertake such a study with the following aims: 1.To examine the influence of exogenous NO on calcium entry and release by addition of NOate donors and over-expression of NOS. 2.To examine the influence of endogenous NO on calcium entry and release by inhibition of NOS with arginine-based inhibitors and possibly RNAi. 3.To examine the influence of endogenous and exogenous NO on calcium oscillations. 4.To examine the transcriptional control of NOS by calcium (using real-time PCR) 5.To investigate the regulation of NOS by calcium signals arising from different sources.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
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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