EMC-2024-4_Murray: Investigating Strategies to Promote Axon Regeneration in Motor Neuron Disease


   Centre for Clinical Brain Sciences

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  Dr L Murray  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This project is on offer as part of the studentship scheme of the Euan MacDonald Centre for Motor Neuron Disease Research. The Euan MacDonald Centre is a multi-disciplinary network of MND researchers across Scotland. A choice of six projects is on offer now for a start date in Autumn 2024, at the University of Edinburgh, St Andrews or Dundee. For more information see www.euanmacdonaldcentre.org/phd-scheme. Euan MacDonald Centre students join our network of >200 MND researchers across Scotland and will have the opportunity to meet people living with MND, participate in academic and public engagement events led by the Centre. To view all the projects offered under this scheme please search for reference numbers EMC-2024-1 to EMC-2024-6.

Promoting axon regeneration in motor neuron diseases such as ALS and SMA, is promising strategy to slow decline and facilitate recovery. To achieve this, it will be critical to promote a permissive environment to allow repair and regeneration of motor axons.

Electric field patterns exist in all tissues and are established during early embryogenesis. These bioelectric signals are transduced by ion channels, and thereby orchestrate embryogenesis. Recent work has shown that exploiting bioelectric mechanisms allow tissue regeneration in scenarios typically considered non-regenerative e.g. allowing regeneration of limb buds in frogs and generation of kidney organoids in vitro. Exploiting knowledge of bioelectric patterns and how they influence development and repair has been applied in nervous tissue to promote regeneration of axons in environments where they would not typically regenerate. From this work, some compounds have emerged with the capacity to generate a more permissive environment to facilitate axon regeneration.

In this project, we plan to test whether these compounds can enhance peripheral and central motor axon regeneration in the contexts of ALS and SMA. We will determine whether bioelectric modulators can enhance regeneration of motor axons in mouse models of motor neuron disease and determine whether they can slow functional decline, improve recovery or ameliorate the neuropathology. 

This project will involve administration of substances to mice, monitoring of phenotypes, analysis of neuromuscular pathology in muscle, nerves and spinal cord using a variety of imaging techniques (fluorescence/confocal microscopy, electron microscopy) and molecular analysis of tissues (i.e. BaseScope, quantitative westerns, qRT-PCR).

Suitable first degree subjects: Any cell biology undergraduate or allied medical degree. 

Biological Sciences (4) Medicine (26)

Funding Notes

The studentship comprises 42 months (3.5 years) stipend payments at the standard UKRI rate, tuition fees and an allowance of £10K per year for three years for consumables and travel. The studentships is open to applicants worldwide. Students will register for the most appropriate degree programme at the University where the project is being offered. It is the applicants’ responsibility to ensure they meet the eligibility requirements for postgraduate study at their chosen University, in terms of academic achievements and English language proficiency.

References

Comley, L. H., et al. (2022). Hum Mol Genet 31(18): 3107-3119.
Marshall, K. L., et al. (2021). Neural Regen Res
Blackiston, D. J., et al. (2015). Neurotherapeutics 12(1): 170-184
Levin, M. (2014). Mol Biol Cell 25(24): 3835-3850

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