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The role of neuromuscular junction (NMJ) degeneration in age-related loss of skeletal muscle mass and function


Project Description

The NMJ (or motor endplate) is a highly specialised chemical synapse that transmits action potentials from motor neurons to muscle fibres. They are essential for normal movement and hence impairment of normal NMJ function results in muscle weakness or paralysis. Disruption of NMJ structure occurs during ageing and is associated with loss of skeletal muscle mass and function although it is currently unclear whether the changes in NMJ are primarily triggered by changes in the motor neuron or the muscle fibre. It is also unknown whether the NMJ disruption plays a causative role in the loss of muscle mass and function during ageing although both human and rodent studies indicate that loss of motor units and motor neurons occur in parallel with muscle fibre loss and loss of muscle function.

Funded by the MRC, BBSRC and US National Institutes of Health, our group are undertaking a comprehensive series of projects to determine the role of the NMJ in regulating signalling pathways that may be beneficial or deleterious to muscle and the PhD studentship will integrate into these projects. Specifically the studentship will utilise cell and in vivo models to determine how disruption of the NMJ occurs during ageing and the effect of this on mitochondrial generation of reactive oxygen species and/or cytokines in denervated and neighbouring innervated muscle fibres,

The student will receive a comprehensive research training in neuromuscular physiology and redox and cytokine biology including exposure to state-of-the-art confocal imaging and molecular approaches. The student will hold a first degree in a relevant biological science with experience of some laboratory-based molecular and biochemical techniques.

The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. We offer a supportive working environment with flexible family support for all our staff and students and applications for part-time study are encouraged. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.

Funding Notes

NO institutional funding for the student stipend or fees for this studentship is available, and a research bench fee of £5000 p.a. will be levied as a contribution to laboratory consumables and expenses.

Enquiries to: Prof M. J. Jackson (email ), Prof A. McArdle () or Dr. A. Vasilaki ()

To apply: please send your CV and a covering letter to Prof Jackson with a copy to

References

1: Sakellariou GK, Pearson T, Lightfoot AP, Nye GA, Wells N, Giakoumaki II,
Griffiths RD, McArdle A, Jackson MJ. Long-term administration of the
mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate
age-related oxidative damage or rescue the loss of muscle mass and function
associated with aging of skeletal muscle. FASEB J. 2016 Nov;30(11):3771-3785.

2: Sakellariou GK, Pearson T, Lightfoot AP, Nye GA, Wells N, Giakoumaki II,
Vasilaki A, Griffiths RD, Jackson MJ, McArdle A. Mitochondrial ROS regulate
oxidative damage and mitophagy but not age-related muscle fiber atrophy. Sci Rep.
2016 Sep 29;6:33944. doi: 10.1038/srep33944.

3: Vasilaki A, Pollock N, Giakoumaki I, Goljanek-Whysall K, Sakellariou GK,
Pearson T, Kayani A, Jackson MJ, McArdle A. The effect of lengthening
contractions on neuromuscular junction structure in adult and old mice. Age
(Dordr). 2016 Aug;38(4):259-272.

4: McDonagh B, Scullion SM, Vasilaki A, Pollock N, McArdle A, Jackson MJ.
Ageing-induced changes in the redox status of peripheral motor nerves imply an
effect on redox signalling rather than oxidative damage. Free Radic Biol Med.
2016 May;94:27-35.

How good is research at University of Liverpool in Clinical Medicine?
(joint submission with Liverpool School of Tropical Medicine)

FTE Category A staff submitted: 143.50

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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