Start of Research Ideas. Idea 1 - All research themes on 1 page with a small button and heading (either in button or above text).
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.
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.
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.
Idea 2 - All projects flowing down on one page. Each project has a column of images (either horizontal or vertical), heading, icons, text. Colour scheme - cerulean, honey, mist. Horizontal images look better in tablet/phone view.
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.
Markers of exercise performance between animal species
Performance markers within human populations
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.
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.