Aquaporins: A gap in our understanding of sarcopenia

Description

Physical frailty, with its associated immobility and disability, is a major factor limiting independence among older people. A key contributor to frailty is a decline in muscle mass and strength (sarcopenia) and the burden of sarcopenia is substantial, with a cost to the NHS of ~£2.5bn/pa. There remains a clear need to identify and test new strategies to reduce the incidence, and consequences, of sarcopenia but the underlying mechanisms remain poorly understood.

Disruption of the neuromuscular junction (NMJ), loss of motor units and a decreased number of muscle fibres is characteristic of sarcopenia. Despite strong associations between the losses of muscle fibres and motor axons, a cause–effect relationship has not been established. My work identified that elevated levels of Hydrogen Peroxide (H₂O₂), a key Reactive Oxygen Species (ROS) is key to this process and this proposed work will examine this using an integrated cellular approach.

It is proposed that the major route of passage of H₂O₂ across cell membranes is by channels called "Aquaporins" (AQPs). Data I generated as a BBSRC-funded Co-I identified that AQPs facilitate H₂O₂ movement in muscle fibres. The NMJ is comprised of the muscle fibre, motor neuron and Perisynaptic Schwann cells (PSCs). Despite the detrimental effects of H₂O₂ on muscle and AQP involvement in control of the H₂O₂ gradient during normal physiological function, there are only sparse reports of AQPs in NMJ-associated cells and no studies examining H₂O₂ transport or the effect of ageing.

We hypothesise that AQPs are the primary means of regulating H₂O₂ movement around the NMJ and that dysregulation of this transport is key to the aberrant production of H₂O₂ resulting in oxidative stress and leading to the development of sarcopenia.

This PhD will provide an ideal opportunity for an individual with an interest in physiology, redox signalling, sarcopenia and neurodegenerative diseases. A range of research methods will be used throughout the project such as confocal imaging, FACS, RNAseq and beyond.

The student will be supervised by Dr. Caroline Staunton in the Musculoskeletal Biology Department, at the University of Liverpool, while also working closely with other students, post-doctoral researchers and academics within the Institute of Life Course and Medical Sciences.

You must have/expect to achieve a 1st or 2:1 honours degree or international equivalent in an appropriate scientific speciality (Biomedical Sciences or similar), a Masters degree in a relevant subject would be advantageous. Application of statistical analysis and use of R is desirable.

Applications should be directed to Dr Caroline Staunton – staunton@liverpool.ac.uk .

To apply, please send:

• A detailed CV,
• Names and contact details of two referees;
• A covering letter highlighting your research experience/capabilities;
• Evidence of your proficiency in the English language, if applicable.