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A joint PhD studentship is available in the Neuroplasticity and Disease lab overseen by Dr Vincenzo de Paola, and the Neurotechnology programme overseen by Professor Kenneth Harris.
The electrical activity of the brain is in a way the visible tip of a large chemical iceberg. It is the brain’s electrical activity that is responsible for our movements and thoughts. But behind the electrical signals, each neuron contains a powerful chemical computer that steers the way the cell integrates and responds to its electrical inputs. Being able to measure chemical signals inside the neurons of a living brain would be a tremendously powerful technique with which to understand the function and dysfunction of the brain. Combined with extracellular measurements of activity and synaptic plasticity, this would allow us to understand how transitions to pathological brain states affect intracellular neuronal chemistry, and the efficacy of candidate therapies in reversing this.
We propose to investigate intracellular chemistry in vivo using the technique of Förster resonance energy transfer (FRET). In FRET, quantum mechanical effects cause transfer of energy between two nearby chromophores, causing a measurable change in fluorescence. Because of the strong dependence of the effect on the distance between the fluorophores, FRET can read out interactions between proteins labelled with fluorophores allowing the spatiotemporal visualization of a wide variety of processes involved in subcellular signalling.
For the current project we will apply this technique to study synaptic chemistry along the lines pioneered in vitro (see references below) by analyzing intracellular cAMP. This molecule is a key player in the transduction of the neuromodulatory signals, and mediator of their effects on neuronal integration and synaptic plasticity. After the technique is established, we propose to combine it with electrophysiological recording and 2-photon imaging of synaptic plasticity. Visualizing cAMP activity in vivo will provide unprecedented information on the way neuronal activity and plasticity are controlled in cortical circuits.
Funding Notes:
This is a fully-funded 3 year PhD studentship at Imperial College, including a competitive stipend and all tuition fees.
Please email your CV and brief statement of interest (one page or less) to vincenzo.depaola@csc.mrc.ac.uk
The deadline for CV submission is midnight on Wednesday 7 March, and interviews will be held on Thursday 15 March.
References:
R. Yasuda et al., Nat Neurosci 9, 283 (2006)
C. D. Harvey, R. Yasuda, H. Zhong, K. Svoboda, Science 321, 136 (2008)
H. Murakoshi, H. Wang, R. Yasuda, Nature 472, 100 (2011)
S. J. Lee, Y. Escobedo‐Lozoya, E. M. Szatmari, R. Yasuda, Nature 458, 299 (2009)
V. O. Nikolaev et al. J Biol Chem 279, 37215 (2004)