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PhD Studentship in Systems Biology: Predictive modelling of sodium channels dynamics in transmission of pain open

PhD Studentship in Systems Biology: Predictive modelling of sodium channels
dynamics in transmission of pain

Location: Streatham Campus, University of Exeter, EX4 4QJ.

Primary supervisor: Dr Najl Valeyev
Secondary supervisors: Dr Piet Van Der Graaf, Pfizer

Voltage-gated sodium channels produce the inward membrane current and are necessary for regenerative action potential production within the mammalian nervous system. They are expressed in primary sensory neurons and have emerged as important targets in the study of the molecular pathophysiology of pain and in the search for new pain therapies.

In order to gain new insights into the underlying molecular mechanisms of action potential alterations causing painful stimuli, we will develop an extended version of the Hodgkin-Huxley model. Our model will establish the link between membrane potential, sodium, potassium and calcium ionic concentrations within and outside the cell and the channel dynamics.

The key objectives of the studentship are to:


•Develop and validate a mathematical model that would combine sodium potassium and calcium ions channels contributing to the action potential eneration relevant to mechanisms of pain.

•Investigate the effects of individual and combined mutation-induced alterations in the current-voltage characteristics of the sodium channels on the action potential eneration. The model will also be employed in order to consider the effects of sodium channels expression, reported in pain states, on the neuronal firing characteristics.

•Utilise the model predictions in order to establish the optimal targeting regime of sodium channels blockers that allows partial or full restoration of homeostasis under the pathologic conditions. The model predictions will be tested in vitro and in vivo by the Biology group in Pfizer.

For informal enquiries, contact Dr Najl Valeyev at N.Valeyev at exeter.ac.uk.

A stipend and home UK fees for 4 years will be awarded.

Application criteria

Applicants should have or expect to achieve at least a 2:1 Honours degree, or equivalent, in maths, physics or biology.

Closing date: Applications are dealt with on rolling basis

posted 2012.06.12