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  A dynamic role for the sodium pump in amyotrophic lateral sclerosis


   School of Psychology

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  Prof K Sillar  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

Na/K exchange pumps are ubiquitously expressed proteins that have been associated with diseases of the motor system including PD and ALS. However, the link between sodium pump dysfunction and disease progression is unknown. Sodium pumps play dynamic roles in regulating spinal motoneuron output due to α3 subunit containing pumps. These have a low affinity for intracellular Na+ and hence are only recruited during intense neural activity to homeostatically hyperpolarize the membrane potential. The underlying mechanism is highly conserved having been described in Xenopus tadpoles and in neonatal mouse. This project will use genetic zebrafish models of ALS to unravel the contribution of α3 subunits (and α2 expressed in neurons and glia) and to track ALS disease progression at the motoneuron and premotor circuit levels. The project, which will involve collaboration with the Becker group at the University of Edinburgh, will provide a broad training in neuroscience techniques ranging from patch clamp electrophysiology of spinal neurons, to molecular genetic manipulations and the developmental expression of specific pump protein subunits.

Prerequisites
Ideally a suitable student will have an honours degree or equivalent in Neuroscience or a related discipline and an understanding of neuronal physiology and molecular genetic approaches. Essential skills would include proficiency in laboratory techniques and analytical methods that can be applied to these areas and the enthusiasm and ability to learn quickly across these areas. Although not essential a Masters in the same area would be an advantage.
Please contact your intended supervisor to discuss the project and your suitability for it before submitting your application.

The project is a part of SPRINT-MND/MS, a new Scotland-wide PhD scheme for research into motor neurone disease and multiple sclerosis. Projects, encompassing a wide range of topics including laboratory, clinical, and social sciences, are available at Aberdeen, Dundee, Edinburgh, Glasgow and St Andrews Universities. This exciting initiative provides a great opportunity for budding researchers in any field related to MND or MS to join Scotland’s network of world-leading scientists and health professionals. Find more information here: http://www.edneurophd.ed.ac.uk/sprint-mndms-phd-programme


Funding Notes

Studentships are for three years and include a standard non-clinical stipend*, UK/EU fees* and an allowance for consumables and travel. The cohort of SPRINT students will also be offered opportunities to attend clinics and meet patients, undertake ‘taster’ placements in a different field, and participate in public engagement and researcher networking events.
*Clinical and/or non-UK/EU applicants are eligible to apply. However, because any shortfall in stipend or fees must be met by the supervisory team, written agreement from the supervisor must accompany the application.

References

Picton, L.D., Nascimento, F., Sillar, K.T. and Miles, G.B. (2017) Sodium pump currents mediate activity-dependent changes in mammalian motor networks. Journal of Neuroscience (in press).
Ohnmacht J, Yang Y, Maurer GW, Barreiro-Iglesias A, Tsarouchas TM, Wehner D, Sieger D, Becker CG, Becker T (2016). Spinal Motor Neurons are Regenerated after Mechanical Lesion and Genetic Ablation in Larval Zebrafish, Development 143: 1464-1474; doi: 10.1242/dev.129155.
Zhang, H.Y., Picton, L.D., Li, W. & Sillar, K.T. (2015) Mechanisms underlying the activity dependent regulation of locomotor network performance by the Na+ pump. Scientific Reports 5, 16188.
Reimer MM1, Norris A, Ohnmacht J, Patani R, Zhong Z, Dias TB, Kuscha V, Scott AL, Chen YC, Rozov S, Frazer SL, Wyatt C, Higashijima S, Patton EE, Panula P, Chandran S, Becker T, Becker CG. (2013) Dopamine from the brain promotes spinal motor neuron generation during development and adult regeneration. Developmental Cell. 2013 Jun 10;25(5):478-91.
Zhang, H., & Sillar, K.T. (2012) Short-term memory of motor network performance via activity-dependent potentiation of Na+/K+ pump function. Current Biology. 22, 526-531.