Applications are invited for a 4-year PhD studentship within a multidisciplinary and enthusiastic research team.
As people age, functionality that involves motor and autonomic neuronal circuits starts to fail which can cause embarrassment (for example associated with a loss of bladder function and control of micturition) or injury (for example many elderly people stumble and fall, leading to broken limbs which prove difficult to heal). The mechanisms underlying this loss of function are little understood but may involve changes in specific ion channels that normally are important in bestowing certain properties on spinal cord neurones. The Kv3 potassium ion channels, found in many spinal cord regions, are associated with fast firing properties and rapidly changing responses. Conditions involving motor dysfunctions can be associated with alterations in the properties of these ion channels. However, no-one has examined whether there are age related changes in these ion channels in the spinal cord, similar to that known to occur in neuronal circuits in the auditory brainstem regions.
The project will involve the use of a number of techniques to examine these potential changes in Kv3 subunit expression during healthy aging. The collaborative nature of the project with Autifony will enable the provision of selective and potent Kv3 channel modulators as pharmacological tools to establish their effects on spinal circuits. This project will examine any changes in the expression of these particular ion channels in the aged spinal cord circuits and will then use new compounds from Autifony that selectively target these ion channels. To gain an understanding of whether these compounds also have effects in the spinal cord, the project will involve recordings from neurones and identifying how they are affected by these modulators. To assess whether age-related changes in levels of ion channels in the spinal cord underlie spinal cord function, the student will then elucidate whether enhancing the effectiveness of the remaining ion channels can restore or improve age related defects in bodily functions that utilise spinal cord circuits, for example urination rates and amounts.
This is a project that will provide the student with experience in a variety of techniques and that could point to new avenues for improving spinal cord function in the aging population. The student will receive training from the supervisors and research teams in both Leeds and Italy, as well as benefitting from the excellent generic training opportunities at the University of Leeds. The project involves a fully funded placement at Autifony, near Verona in Italy for a minimum of 3 months where they will learn about the development of new compounds and further electrophysiological techniques.
Applicants should have a strong neuroscience background, some laboratory experience (electrophysiology or immunohistochemistry if possible), excellent communication skills and evidence of an ability to work well within a team or independently.
This 4-year full-time studentship provides full support for UK/EU tuition fees and an annual tax-free stipend at standard RCUK rate (for an October 2014 start). The project is open to UK/EU* nationals (who have resided in the UK since at least 1 September 2011) due to the nature of the funding.
Applications should be made through https://studentservices.leeds.ac.uk/pls/banprod/bwskalog_uol.P_DispLoginNon
Please include: CV, academic transcripts, details for two referees, A covering letter outlining your suitability for this studentship, what you hope to achieve from the PhD and your research experience to date
Any enquiries should be directed to Dr Susan Deuchars.
Pertinent references produced by past PhD students on Kv3.1b or reviews on spinal cord circuitry:
Edwards, IJ, Bruce, G, Lawrenson, C, Howe, L, Clapcote, SJ, Deuchars, SA (CA) and Deuchars J (2013) Na+/K+ ATPase α1 and α3 Isoforms Are Differentially Expressed in α- and γ-Motoneurons. Journal of Neuroscience 33(24):9913-9.
Deuchars, S.A. (2007) Multi-tasking in the spinal cord - do "sympathetic" interneurones work harder than we give them credit for? Journal of Physiology 580(Pt 3):723-9. Topical review.
Dallas M.L., Atkinson L., Milligan C.J., Morris N.P., Lewis D.I., Deuchars S.A. and Deuchars J. (2005). Localisation and function of the Kv3.1b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarius. J Physiol. 562(Pt 3):655-72
Deuchars, S.A., Brooke, R.E., Frater, B. and Deuchars, J. (2001). Properties of interneurones in the intermediolateral cell column of the rat spinal cord: role of the potassium channel subunit Kv3.1. Neuroscience 106 (2), 433-446
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