Centre for Neuroscience Research, University of Edinburgh
Hugh Robson Building, George Square


EH8 9XD - Edinburgh
United Kingdom

+44 (0)131 650 7961 (office); 7960 (lab)
+44 (0) 131 650 6576
giles.hardingham@ed.ac.uk

Job opportunities

In neurons, Ca2+ entry through the NMDA receptor (NMDAR) is a major source of synaptically-evoked Ca2+ transients and directly affects neuronal survival/ death: while too much NMDAR activity is harmful, so is too little. My group is interested in understanding the mechanisms behind this dichotomous signalling. A significant part of our work concerns the mechanisms and consequences of signalling to gene expression, since this is an important route by which pro-survival changes to neurons are effected.  Specifically, our work comprises 3 themes, each supported by project grants:
1.Identification of the genes induced or suppressed by synaptic NMDAR activity which are responsible for activity-dependent neuroprotection.
2. Investigation of a novel mechanism we uncovered by which synaptic NMDAR activity can de-repress genes by triggering the nuclear export of broad specificity transcriptional corepressors.
3. Investigating the differences in Ca2+ signalling to pro-survival and pro-death events, and using this knowledge to assess ways of interfering with pro-death NMDAR signalling without affecting the important pro-survival signalling cassettes.

Soriano, F. X., Papadia, S., Hofmann, F., Hardingham, N., Bading, H., Hardingham, G. E. (2006):Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability..Journal of Neuroscience: 26, 4509-18

Papadia, S., Stevenson, P., Hardingham, N. R., Bading, H., and Hardingham, G. E. (2005):Nuclear Ca2+ and the CREB family mediate a late-phase of activity-dependent neuroprotection..Journal of Neuroscience: 25, 4279-87

Hardingham, G.E., Hilmar Bading (2003):The Yin and Yang of NMDA receptor signalling..Trends in Neurosciences: 26, 81-89. Refereed review

Hardingham, G.E., Y Fukunaga & H Bading, H. (2002):Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways..Nature Neuroscience: 5, 405-414

Hardingham, G.E. F. Arnold, F. and H. Bading, H. (2001):Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity..Nature Neuroscience: 4. 261-267