The research of the Grounds & Shavlakadze Muscle Group is focussed on skeletal muscle research. 4 areas are outlined here, but many projects can be developed with the student.

Key personel: this is collaborative research between A&HB and BBCS, involving Prof. Miranda Grounds, Dr Thea Shavlakadze, Prof. John McGeachie, Dr Peter Arthur, Dr Ahmed Elshafey and PhD students Jessica Terrill, Ruth (Jinfen) Chai, Pearl Tan, Hatice Tohma.

Background. Skeletal muscles constitute approximately 40% of the mass of the human body and are essential for all aspects of movement such as breathing, eating, posture, walking and reflexes as well as heat generation and metabolism. A loss of muscle mass, known as atrophy or wasting, has major consequences for strength and muscle function. Muscle wasting can result from disuse (e.g bed rest or space travel), injury, starvation, diseases such as cancer, sepsis, neuromuscular disorders, and also ageing. Different factors contribute to muscle wasting in the various conditions. The progressive loss of muscle mass associated with ageing is known as sarcopenia and is the focus of this research. Sarcopenia results from a decrease in myofibre size, combined with a loss of myofibres and changes in myofibre types. Between the ages of 50 and 80 in humans, muscle mass is reduced by about one-third; this is a major contributing factor to increased falls and fractures, with impaired physical function (frailty) resulting in dependency and sometimes death.

Development of new targeted interventions to reduce sarcopenia and frailty would have a major impact on reducing health system costs, as well as improving the quality of life for the growing population of older individuals. In order to develop appropriate interventions to reduce muscle-wasting we need to understand the key factors responsible for sarcopenia. This is the focus of our current research.

Projects. We have many current projects related to muscles in very old (geriatric) mice aged up to 30 months of age and the development of potential therapies. These include transgenic mice and other interventions related to insulin-like growth factor-1 (IGF-1) combined with exercise, the pro-inflammatory cytokine Tumour Necrosis Factor (TNF) and oxidative stress (e.g using over-expression of catalase). We are examining not only skeletal muscles but the hearts, brains and neuronal systems of these ageing mouse models.

Techniques used range from microscogy and immunostaining, histological and morphometric analyses of tissues, many molecular techniques including qPCR and phosphoprotein signalling, tissue culture studies and various measurements of oxidative stress.

We also collaborate with the physiologists Drs Gavin Pinniger and Anthony Bakker to study functional properties of muscles (in vivo and ex vivo) with respect to the above interventions.

In addition we have new projects to examine the capacity of geriatric muscles to regenerate after injury and form new muscles – reflecting the muscle precursor (stem) cell capacity of old skeletal muscles.

In discussion with the student we can select projects to best suit their interests.