Prof Gareth Miles
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Changes in the excitability of motoneurons represent an early hallmark of Motor Neuron Disease (MND) that has been reported in animal models, human patients and more recently in human induced pluripotent stem cell (iPSC) based models of the disease (1,2). Both hyperexcitable and hypoexcitable motoneuron states have been reported, with hyperexcitability typically thought to precede hypoexcitability. However, controversy remains regarding the contribution of altered excitability to motoneuron loss in MND. For example, although changes in excitability are most often thought to be neurotoxic, some work supports a neuroprotective role for increased excitability (3). To further investigate the role of motoneuron excitability in MND and its potential usefulness as a target for novel therapeutics we aim to: (i) determine the effects of manipulating (up and down) the excitability of motoneurons derived from iPSCs of healthy individuals and MND patients; and (ii) investigate the actions and potential benefits of agents that can modulate the ion channels that likely underlie changes in motoneuron excitability in MND. This project will involve the use of cutting edge iPSC technology alongside patch-clamp electrophysiology and live calcium imaging. We expect to reveal important insights into disease mechanisms and highlight targets for new treatment strategies for this devastating disease.
Prerequisites
A background in neuroscience would be preferred but experience in other relevant biomedical sciences may also be appropriate. Some laboratory experience is desirable.
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
1. Quinlan KA (2011) Links between electrophysiological and molecular pathology of amyotrophic lateral sclerosis. Integr Comp Biol 51:913–925.
2. Devlin A-C, Burr K, Borooah S, Foster JD, Cleary EM, Geti I, Vallier L, Shaw CE, Chandran S, Miles GB (2015) Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability. Nat Commun 6:5999.
3. Saxena S, Roselli F, Singh K, Leptien K, Julien J-P, Gros-Louis F, Caroni P (2013) Neuroprotection through Excitability and mTOR Required in ALS Motoneurons to Delay Disease and Extend Survival. Neuron 80:80–96.
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