2012 Projects available for UK students (BBSRC) and also non-UK residents funded by a prestigious Marie Curie Initial Training Network (ITN)**
Neuroprotective gene expression for combating oxidative stress and synaptic dysfunction
Many acute and chronic neurodegenerative conditions are associated with oxidative stress. However, trials with small molecule antioxidant compounds have met with limited success. Attention is now shifting to understanding how intrinsic neuronal antioxidant defences can be controlled and manipulated for therapeutic benefit. This project will uncover novel mechanisms by which neurodegeneration can be prevented through controlling the brain' s antioxidant defences and other neuroprotective pathways. Preliminary data has revealed important insight into how oxidative stress interferes with neuronal function, including synaptic physiology. Moreover, we have defined transcriptional programs, initiated by synaptic activity, that boost the capacity of key antioxidant systems. The project will take a multidisciplinary approach and will involve the candidate gaining experience in a diverse array of techniques, including live cell imaging, electrophysiology molecular biology, human stem cell biology, working with transgenic animals and experience with in vivo manipulations and models. From this project, new therapeutic directions will emerge to combat neurodegeneration.
references
Bell ..and Hardingham(2011) Mild oxidative stress activates Nrf2 in astrocytes which contributes to neuroprotective ischemic preconditioning. PNAS 108.
Hardingham and Bading (2010). Synaptic vs. extrasynaptic NMDAR signalling: implications for neurodegenerative disorders. Nat Rev Neuro 11 p682
Léveillé..and Hardingham (2010). Suppression of the intrinsic apoptosis pathway by synaptic activity. J. Neurosci 30. p263
Papadia... and Hardingham (2008). Synaptic NMDAR activity boosts intrinsic antioxidant defences. Nat. Neuro 11, p476"
Contact InformationNeuroprotective gene expression for combating oxidative stress and synaptic dysfunction
Many acute and chronic neurodegenerative conditions are associated with oxidative stress. However, trials with small molecule antioxidant compounds have met with limited success. Attention is now shifting to understanding how intrinsic neuronal antioxidant defences can be controlled and manipulated for therapeutic benefit. This project will uncover novel mechanisms by which neurodegeneration can be prevented through controlling the brain' s antioxidant defences and other neuroprotective pathways. Preliminary data has revealed important insight into how oxidative stress interferes with neuronal function, including synaptic physiology. Moreover, we have defined transcriptional programs, initiated by synaptic activity, that boost the capacity of key antioxidant systems. The project will take a multidisciplinary approach and will involve the candidate gaining experience in a diverse array of techniques, including live cell imaging, electrophysiology molecular biology, human stem cell biology, working with transgenic animals and experience with in vivo manipulations and models. From this project, new therapeutic directions will emerge to combat neurodegeneration.
references
Bell ..and Hardingham(2011) Mild oxidative stress activates Nrf2 in astrocytes which contributes to neuroprotective ischemic preconditioning. PNAS 108.
Hardingham and Bading (2010). Synaptic vs. extrasynaptic NMDAR signalling: implications for neurodegenerative disorders. Nat Rev Neuro 11 p682
Léveillé..and Hardingham (2010). Suppression of the intrinsic apoptosis pathway by synaptic activity. J. Neurosci 30. p263
Papadia... and Hardingham (2008). Synaptic NMDAR activity boosts intrinsic antioxidant defences. Nat. Neuro 11, p476"
Professor Giles Hardingham
University of Edinburgh
School of Biomedical Sciences
Hugh Robson Building, George Square
EH8 9XD Edinburgh
UK
Phone: +44 131 6507961
Fax: +44 131 650 6527
E-mail: giles.hardingham@ed.ac.uk
Closing date: 2012-12-31
Website: http://www.ed.ac.uk/schools-departments/integrative-physiology/staff-profiles/giles-hardingham
