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RESEARCH OVERVIEW

The MyoLab’s research focuses primarily on skeletal muscle function – structure, metabolism and contraction. Although the research fields overlap, we can divide it into four main categories, each with unique projects answering specific questions.

Nature or Nurture

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This research area focuses on establishing when genetics cease to play a role in determining exercise performance. The models we use include the various ethnicities of the world, as well as wild and domestic animals of the African continent.

Muscle Weakness

The mechanisms by which muscle weakness comes about from various diseases, are poorly studied. This component of our research focusses on using single fibre technology to investigate what exactly is affected by diseases such as McArdle’s disease and inflammatory myopathies (cardiac and skeletal muscle). We are also developing novel methodologies to accurately diagnose malignant hyperthermia in South Africa.

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Nature or Nurture

How much do genetics contribute to the performance of athletes? Or can specific training increase performance for all humans? Are athletes born great or made great?

Scientists have been looking for that key gene for decades. But each time a new gene shows an association with some performance measure, the hypothesis gets thwarted by another. However, there is no doubt that your genetic makeup plays a significant role in sporting performance. By merely looking at the different mammalian species, one sees a diversity of fast runners, runners that have endurance, or those with brut strength. Even within species, there are vast differences: certain horse breeds are fast sprinters, some again known for their endurance ability. The same can be said about the various dog breeds – a grey hound vs. a bull dog. There is something inherent that brings these attributes to the surface, but is still unknown.

Projects

Markers of exercise performance between animal species

Mother Nature has some pretty fast, strong and scary animals. Humans actually fall into the category of being the slowest and weakest. Species are formed as a result of small genetic differences. Mammals share a number of genes that are similar, with only very small differences in their genetic code. Comparatively, there are vast differences between land mammals on a morphological level. These include size, stature, muscle mass and limb length, to name but a few. But, given the vast number of animal species, their muscles are very poorly studied – only 0.9% of the 5500 mammal species have been studied on a muscular level.

The Myolab has already made some significant headway in studying muscle contractility, metabolism and structure of some African wildlife species. For starters, the cat species (lion, caracal and cheetah) have more than 50% type IIX muscle fibres, whereas the same muscle in humans contain between 5 – 20%. The prey of these wild cats, that includes the springbok, kudu, mountain reedbuck, blesbok and fallow deer, also has more than 50% type IIX fibres. In fact, one type IIX single fibre from either the caracal or lion can produce three times the amount of power that the human equivalent! To produce this exceptional power, these animals must rely on efficient and an abundance of ATP generated from their muscle metabolism. Collectively, the cats and antelopes have a very high capacity to burn carbohydrates in the form of glycogen and blood glucose. However, this is where the prey has the advantage: they all have many more mitochondria in their muscle. In essence, the prey have speed and endurance whereas the cats only have speed. These findings confirm why cats need to stalk their prey and kill quickly. Once the antelope gets away and starts running, the odds of catching it becomes very poor.

Collaborators on this extensive project include Faculty of Veterinary Science, University of Pretoria; City of Cape Town etc ....

Performance markers within human populations

Although a very sensitive topic, science has observed that specific populations seem to perform better in sports than others. It also holds true for certain diseases, such as sickle cell anaemia and even most recently, susceptibility to diabetes. Kenyan and Ethiopian runners dominate the world of endurance running, whereas Jamaican and African-American runners dominate the short sprinting events. There are various internal and external factors that contribute to their success. There has been lots of speculation surrounding the performance advantage, being it genetics or environmental, but thus far, no genetic marker(s) (i.e. intrinsic) can explain these advantages in sporting success. Nevertheless, the human body can very easily and relatively quickly adapt to various forms of exercise, such as altered training loads and the environment (hot vs. cold, altitude, etc.). Thus, just because one group excels in a specific sport, does not necessarily mean that their success is genetic. Exposure to the sport, training volume and intensity, and motivation are factors that can significantly influence performance. However, to what extent these factors can push the human body to its limits and bring about the physiological adaptations, are still unclear and must be investigated.

There are only a handful of studies that investigated the physiology between athletes, in particular endurance runners. The overall consensus thus far is that African runners exhibit lower blood lactate at the same running intensity than their European counterparts. Secondly, it appears that African runners have a larger proportion of type IIA muscle fibres. Combined, these two factors should theoretically result in greater force output and a longer time to fatigue. However, whether improved performance is indeed as a result of these two factors needs to be further investigated.

Research investigating the effect of nature or nurture on exercise performance in animal and human populations is ongoing within the Myolab. Should you require more information or are interested in pursuing an MSc or PhD, please contact the Myolab.

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Muscle Weakness

Myopathy literally means “muscle disease”. Any condition that negatively affects muscle performance can be seen as a myopathy. In humans and animals, they can arise from a wide variety of hereditary and/or acquired causes. These include abnormalities in i) structural proteins (e.g. muscular dystrophies), ii) impaired muscle metabolism (e.g. disorders of carbohydrate or fat metabolism) or iii) immune-mediated inflammation (e.g. polymyositis, dermatomyositis). The primary feature of all these different abnormalities is that of muscle weakness that affects predominantly large muscle groups like the hip, thigh or shoulder muscles.

PROJECTS

Understanding inflammatory myopathies and weakness - Why are inflamed muscles weak?

Idiopathic inflammatory myopathies (IIMs) are a group of muscle disorders caused by an immune-mediated attack on skeletal muscle tissue, and consist of polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), non-specific inflammatory myopathy (NIM) and necrotising autoimmune myopathy (NAM). All these myopathies present with some level of weakness. The exact mechanism of weakness in IIMs is still unknown, but may theoretically be from a decrease in the actual number of muscle fibres, decreased contractility (performance) of the individual muscle fibres, or both. To date, it has been assumed this weakness result from a decrease in the number of muscle fibres as a result of necrosis. It is due to this assumption that the fibre contractility has been poorly studied. Only one study has looked at the muscle fibres’ function in untreated DM and IBM. However, this study had a number of flaws. Also, a number of observations argue against necrosis as the only factor contributing to the weakness. These include:

☆ a lack of correlation between weakness and the degree of inflammation in muscle,
☆ the relatively small amount of necrotic fibres on muscle histology as compared to the degree of weakness, and
☆ how quickly patients respond to the treatment with corticosteroids.

Other non-immune effects on muscle may also contribute significantly to weakness in IIMs by affecting the contractile apparatus. These include an acquired deficiency of AMP-deaminase 1 (possibly interleukin-1 mediated) and depression of muscle fibre contractility by tumour necrosis factor α (TNF-α), as suggested by animal studies. Furthermore, the mechanism by which corticosteroids improve muscle function is also poorly studied. Possible explanations include the inhibition of secretion of TNF-α and decreased levels of TNF-α receptors, as well as increased AMP-deaminase 1 enzyme via decreased expression of interleukin-1.

We are currently comparing the contractile properties of single muscle fibres from patients with untreated IIMs to those of healthy volunteers. Apart from the functional single fibre tests, we are also assessing a number of proteins (as mentioned above) in the muscle. We have recently performed the first training study on a participant with advanced stage inclusion body myositis (IBM) and the data has made us very excited.

Establishing the single fibre in vitro contracture test in Africa