Research Bio
The cellular actions of many neurotransmitters and hormones are dependent on receptor-activated increases in intracellular calcium concentrations in their target cells. In various secretory and other "non-excitable" cells, the physiologically relevant signals often take the form of a series of Ca2+ oscillations, and many critical cellular responses are tuned to respond to the specific frequency of such oscillations. A key factor in sustaining these signals and determining their frequency, is the receptor-activated entry of Ca2+ from the extracellular medium. Our research concerns the nature of the conductances responsible for this entry, and their specific roles in modulating the overall Ca2+ signal. Specifically, our recent research has focused on the ARC channel –
a novel Ca2+ entry channel that is activated by the receptor-mediated generation of arachidonic acid, and which we first described a few years ago. Importantly, it is this channel that appears to play the major role in the entry of Ca2+ during the generation of the oscillatory Ca2+ signals in several cell types. We have recently characterized the key molecular components of this channel, revealing that it is a member of a new family of channels – the "Orai-based channels". This molecular characterization has opened up new opportunities for the analysis of its nature, mechanism of activation, and regulation. This, along with identifying how the Ca2+ entering via this channel acts to modulate the frequency of the agonist-induced Ca2+ oscillations, forms the major focus of our current research.
Techniques used include patch-clamp analysis of ion-channel activity, digital imaging, real-time confocal imaging, and photon-counting microfluorimetric measurements of intracellular Ca2+ concentrations in single cells, and biochemical and molecular studies of the proteins that form the channel and its regulators.
| Session Chair - Salivary Glands and Saliva Gordon Research Conference, Ventura, CA. |
2003 |
| Session Chair - 5th UK Calcium Signalling Conference, Liverpool, England. |
2003 |
| Session Chair - Professor Sir Michael Berridge Retirement Conference, Cambridge, England. |
2003 |
| Session Chair - International Workshop on "Experimental and Theoretical Calcium Dynamics" Max-Planck institute for the Physics of Complex Systems, Dresden, Germany |
2000 |
| Session Chair - Experimental Biology 1993 (FASEB) meeting, New Orleans |
1993 |
| Session Chair - Joint Meeting of the APS, ASZ, CSZ and SEB, Cambridge, England |
1992 |
| Session Chair - International Symposium on "Mechanisms of Systemic Regulation in Lower Vertebrates", Göttingen, Germany |
1990 |
| Session Chair - Society for Experimental Biology Conference, York, U.K. |
1987 |
| Session Chair - IUPS International Congress, Vancouver, Canada |
1986 |
| Session Chair - IUPS Satellite Symposium on "Membrane Transport and Control: Comparative Mechanisms", Banff, Canada |
1986 |
| Session Chair - Society for Experimental Biology Conference, Bangor, U.K. |
1985 |
| Session Chair - Society for Experimental Biology Conference, Cardiff, U.K. |
1984 |
| Session Chair - Seminar Series Symposium of the Society for Experimental Biology, Durham, U.K. |
1981 |
| Session Chair - Society for Experimental Biology Conference, Lancaster, U.K. |
1979 |
| Science Research Council Fellowship (U.K.), University of Lancaster, England |
1972 - 1974 |
| University of Otago Teaching Fellowship, University of Otago, New Zealand |
1969 - 1972 |
2012 Apr 14
Palk L, Sneyd J, Patterson K, Shuttleworth TJ, Yule DI, Maclaren O, Crampin EJ. "Modelling the effects of calcium waves and oscillations on saliva secretion." Journal of theoretical biology. 2012 Apr 14; 305CEpub 2012 Apr 14. |
2012 Jan 15
Shuttleworth TJ. "Orai3--the 'exceptional' Orai?" The Journal of physiology. 2012 Jan 15; 590(Pt 2):241-57. Epub 2011 Oct 31. |
2011 Nov 1
Thompson JL, Shuttleworth TJ. "Orai channel-dependent activation of phospholipase C-?: a novel mechanism for the effects of calcium entry on calcium oscillations." The Journal of physiology. 2011 Nov 1; 589(Pt 21):5057-69. Epub 2011 Aug 30. |
2010 Oct 21
Palk L, Sneyd J, Shuttleworth TJ, Yule DI, Crampin EJ. "A dynamic model of saliva secretion." Journal of theoretical biology. 2010 Oct 21; 266(4):625-40. Epub 2010 Jun 25. |
2010
Thompson JL, Mignen O, Shuttleworth TJ. "The N-terminal domain of Orai3 determines selectivity for activation of the store-independent ARC channel by arachidonic acid." Channels (Austin, Tex.). 2010 4(5):398-410. Epub 2010 Sep 01. |
