RESEARCH
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. These are: Nature or Nurture; Obesity, lifestyle and insulin resistance; Muscle weakness and Exercise-induced muscle pathologies.
There is no doubt that your genetic makeup plays a significant role in sporting performance. By merely looking at the different mammal species, one sees a diversity of fast runners, endurance runners, or those with brute strength. Even within species, there are vast differences: certain horse breeds are fast sprinters, some again are known for their endurance ability. The same can be said about the various dog breeds – e.g. a grey hound vs. a bull dog. There is something inherent that brings these attributes to the surface, but what this is, is still unknown.
Current projects
Question: Mother Nature has some pretty fast, strong and scary animals. Humans are unfortunately the slowest and weakest. Mammals share a number of genes, with only tiny differences in their genetic code. However these small differences give rise to major morphological diversity. Given the vast number of animal species, their muscles are poorly studied – only 0.9% of the 5 500 mammal species have been studied on a muscular level.
Research: We have 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, while humans contain between 5 – 20%. Their prey (including the springbok, kudu and blesbok) also have more than 50% type IIX fibres. And, one type IIX single fibre from either the caracal or lion produce 3x more power than their human equivalent! To produce this exceptional power, these animals must rely on efficient energy (i.e. ATP) production in their muscle. The big cats and antelopes have a very high capacity to burn carbohydrates, but the antelope have lots more mitochondria, also fuelling endurance ability. Therefore, the antelope have speed and endurance whereas the big cats only have speed. It is for these reasons that the big cats need to stalk their prey and kill quickly because there is no stopping the antelope once it gets away.
Question: 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 recently, susceptibility to diabetes. Kenyan and Ethiopian runners dominate the world of endurance running, while Jamaican and African-American runners dominate in short sprints. There has been lots of speculation surrounding the performance advantage, being it genetics or environmental, but thus far, no genetic marker(s) can explain these advantages. Nevertheless, the human body can very easily and relatively quickly adapt to various forms of exercise. Exposure, 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.
Research: There are only a handful of studies that have investigated the physiology between athletes, in particular endurance runners. The consensus thus far is that African runners exhibit lower blood lactate at the same running intensity than their European counterparts, and they also appear to 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 is what we are investigating.
Today, humans are leading a more sedentary lifestyle, consuming the typical urbanised diet rich in refined sugars and processed foods. Our lifestyle choices have led to an obesity epidemic that is causing the dramatic rise in insulin resistance and type II diabetes. Furthermore, it appears that animals, domestic and wild, are also at risk of developing diabetes.
Current projects
Question: Observations of baboons in the Cape Peninsula, within the City of Cape Town, have hinted that some may be suffering the consequences of poor diet, just as humans are. Baboon monitors (humans that act as baboon police) have reported that some of these regular raiders are becoming overweight and lethargic, with some showing signs of hair- and teeth-loss. Apart from the physical symptoms observed, the baboons that are consuming processed foods high in sugar and fat may also run the risk of developing insulin resistance and type II diabetes.
Research: This project investigated whether Cape Towns’ urban baboons are eating their way towards developing insulin resistance and type II diabetes. We compared the results with baboons that were never exposed or had access to human foods (i.e. rural baboons). We specifically measured the glucose transporters and insulin signalling complex within skeletal muscle, as these pathways easily become resistant to insulin. It was found that the urban Cape Peninsula baboons were heavier, had more teeth problems and had lower active insulin receptor complexes than their rural counterparts. To conclude, the consumption of foods high in sugar and fat may put the Cape Peninsula baboons at risk of developing insulin resistance and diabetes. This project is still ongoing with the City of Cape Town and Cape Nature.
Question: Dogs are believed to develop a form of diabetes that is similar to type 1 diabetes in humans. Breed seems to be a risk factor for diabetes with various breeds showing different predispositions to the disease. For example, Samoyeds, Swedish Elkhound, Lapphund, Fox Terriers, Australian Terriers, Pugs and Poodles are at a higher risk of developing diabetes. Golden Retrievers, German Shepherds, Cocker Spaniels, Collies and Boxers are at a lower risk for developing the disease. Cats are believed to have a form of diabetes similar to type 2 diabetes in humans, with obesity being a major risk factor. It may be that the breed of your cat or dog may be a risk factor in developing diabetes, but what causes this predisposition is still unknown. With the vital role of skeletal muscle in glucose regulation, and the link between fibre type and insulin sensitivity, could the answer lie in the muscle?
Research: Skeletal muscle morphology (fibre type distribution and cross sectional area) and metabolic activity have been investigated in 16 breeds of healthy domestic dogs. It was found that dogs have a high oxidative capacity (which aligns to the literature), although a high variation was seen across breeds. This study is still ongoing, with further investigation required into domestic cats and diabetic populations.
Question: Confining wild animals is a practice implemented for a number of reasons, but primarily for the protection and conservation of endangered species. The dietary needs of the big wild cats (e.g. lions, cheetahs, leopards) are not yet well understood and may predispose these animals to metabolic disease. In a group of captive lions, body weight was found to be highly skewed as the lions were grossly overweight. Furthermore, as a result of routine feeding, the need for behavioural activities of hunting and chasing prey have been removed, causing these lions to become inactive and lethargic. Along with lions, there are various other felid species, such as caracals, cheetahs, leopards and lynxes that reside in captivity. Each of these species differ in their biochemical and genetic makeup, and therefore may have different nutritional needs.
Research: We have collected muscle samples from 87 lions, with 7 being wild and the rest from sanctuaries. Additionally, we also collected samples from 36 cheetahs. The samples are being processed for: fibre morphology, fat content, metabolism, insulin signalling pathway and glucose transport.
Question: Gastritis is a chronic disease that affects more than 90% of cheetahs in captivity. Recent pilot data suggests that a dietary glycine deficiency could play a role in the pathogenesis of this disease. Glycine is a simple amino acid that plays a key role in various tissue metabolic pathways. However, it is not known whether the addition of this simple amino acid to the diet of captive cheetahs will have an effect on these various tissues and their overall metabolism of cheetahs.
Research: The effect of glycine supplementation on the metabolism of skeletal muscle, blood and urine in cheetahs will be investigated in 10 captive cheetahs. The study is a cross-over design with cheetahs being supplemented with glycine for four weeks, and samples being collected before and after the intervention. We will use a number of techniques to determine the mechanism of how a simple molecule like glycine has such an enormous effect on the health of cheetahs. Our analyses will primarily focus on whole body metabolism (through metabolomics analyses) and skeletal muscle. This study was done in collaboration with Cango Wildlife Ranch in Oudtshoorn, Western Cape.
Myopathy literally means “muscle disease”. 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). 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.
Current projects
Question: Idiopathic inflammatory myopathies (IIMs) are a group of muscle disorders caused by an immune-mediated attack on skeletal muscle tissue, and consist of polymyositis, dermatomyositis, inclusion body myositis, non-specific inflammatory myopathy and necrotising autoimmune myopathy. All these myopathies present with some level of weakness. This weakness may theoretically be from a decrease in the actual number of muscle fibres, decreased contractility of the individual muscle fibres, or both. To date, it has been assumed this weakness results 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. A number of observations argue against necrosis as the only factor contributing to this weakness:
- a lack of correlation between weakness and the degree of muscle inflammation,
- 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.
Research: 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 in the muscle. We have recently performed the first training study on a participant with advanced stage inclusion body myositis (IBM) and the data is very promising.
Question: Malignant hyperthermia (MH) is a fatal condition triggered by volatile anaesthetic agents. The cause of MH is due to mutations in the ryanodine receptors, located in the sarcoplasmic reticulum, causing increased sensitivity to caffeine and certain anaesthetics. This triggers the release of calcium, leading to involuntary muscle contractions and elevated body temperatures. Although patients who have a reaction during anaesthesia would be genetically screened using a blood sample, these mutations can easily go undetected. The only sure way to establish an individual’s susceptibility to MH, is to perform a muscle biopsy and subject it to the In Vitro Contracture Test (IVCT). This invasive test requires a large muscle sample (≈30 mm in length and 3 – 5 mm thick) which may lead to a painful healing process and scarring. The IVCT test itself requires the muscle to be bathed in a solution containing caffeine and halothane. If muscle contraction starts before the recommended threshold, the patient is usually classified as MH susceptible.
Research: Technology has since evolved so that contracture tests may be performed on single isolated muscle fibres. The upside of this technology is that a very small muscle biopsy may be sufficient (5 mm in length). The MyoLab has embarked on developing, establishing and validating a single fibre technique to assist in diagnosing MH.
Question: A number of metabolic myopathies exist that causes a bottle neck in supplying the necessary ATP for muscle contraction and relaxation. Each myopathy is unique in causing weakness, but whether the mutation actually affects the contractile apparatus (fibre type, myosin-actin interaction), is still vague.
Research: The MyoLab is currently investigating how contractility is affected, at a whole muscle and single muscle fibre level in metabolic myopathies, and how exercise training may help in improving strength in these patients. This research is in partnership with local and international institutions.
After an exercise bout, your muscles may become stiff and sore, a typical delayed onset of muscle soreness. This is not caused by lactate build-up (the myth has been busted), but actually by small muscle tears that cause the content of the muscle fibres to leak into the blood stream. This response is normal for any mammal after exercise and our bodies adapt to these stresses quite quickly. Severe muscle damage and its breakdown can lead to a potentially fatal condition collectively known as rhabdomyolysis. However, there are many situations where the duration of exercise was just too short to explain the severe rhabdomyolysis.
Current projects
Question: Capture myopathy is a condition that appears primarily when wild animals are captured, and has major financial implications in the wildlife industry. Signs of capture myopathy include:
- high body temperature (>42°C),
- muscle spasms, stiffness and lameness,
- stumbling and loss of appetite, and
- the appearance of dark coloured urine – a clear sign of muscle breakdown and kidney damage.
The survival rate of these animals, once they have progressed to the stage of dark urine, is very low. To date, the exact cause of capture myopathy is largely unknown, but many arguments have been put forward and range from species being more susceptible, genetic mutations, nutritional deficiencies or a lack of physical fitness. There is also no known treatment for this condition.
Research: Our research team is combining skills, technologies and techniques from the veterinary and exercise science disciplines, to search for the causes and preventative measures of capture myopathy. Since 2009, we have studied the skeletal muscle of a number of species, including lion, caracal, springbok, kudu, blesbok and black wildebeest. In 2014, we stressed antelope and cooled some with ice water to see whether this may have an effect on the pathology. After this study, we also conducted the first training study, where antelope were physically trained for 4 weeks. These projects are still ongoing.
If you are interested in pursuing an MSc or PhD in any of these categories, or would like more information please contact the MyoLab.