The Influence Of Alpha Actinins On Human Performance
Funder
National Health and Medical Research Council
Funding Amount
$542,500.00
Summary
There is a wide variation in skeletal muscle function in the general population. At one end of the spectrum are elite athletes who excel in a specialised area of sprint, power or endurance performance, while at the other end of the spectrum are individuals with muscle weakness due to inherited muscle disease. Part of this variation in human muscle performance is due to the genetic makeup of the individual. For example, world class sprinters have muscles which are genetically predisposed to gener ....There is a wide variation in skeletal muscle function in the general population. At one end of the spectrum are elite athletes who excel in a specialised area of sprint, power or endurance performance, while at the other end of the spectrum are individuals with muscle weakness due to inherited muscle disease. Part of this variation in human muscle performance is due to the genetic makeup of the individual. For example, world class sprinters have muscles which are genetically predisposed to generate maximal force at high speed. Similarly, the severity of muscle disease in an affected individual is influenced, in part, by other genes that affect normal muscle performance. The genes responsible for normal variations in muscle function in humans are unknown. The alpha-actinins are structural components of skeletal muscle. The two forms of alpha-actinin in skeletal muscle interact with a number of proteins involved in human muscle disease and thus likely contribute to the severity of muscle weakness in affected patients. Alpha-actinin-3 is present only in fast (type 2) fibres - the muscle fibres responsible for perfomance at high speed. We have identified a genetic change that results in absence of this protein in 1 in 5 people in the general population, without causing disease. We now have evidence that this genetic change, and hence whether or not muscle contains alpha-actinin-3, influences muscle performance in elite athletes. We will now use a variety of approaches to study the alpha-actinins in normal and diseased skeletal muscle. We will study the effect of changes (mutations) in the alpha-actinins in the muscle cells grown in the laboratory and in animal models. This work will impact on our understanding of how normal skeletal muscle functions, and the factors that influence human diversity in the general population.Read moreRead less
Genetic Control Of Susceptibility To Autoimmune Gastritis
Funder
National Health and Medical Research Council
Funding Amount
$346,945.00
Summary
Autoimmune gastritis is caused by the immune system targeting and destroying the stomach lining. We have developed a mouse model of the causes of gastritis and mapped the two major genes that can control susceptibility. This project involves the final stages of identifying these genes and determining how they cause disease.
Melanoma is one of Australia s major cancer problems, but we still do not completely understand why certain people are at higher risk than others. This study is focussed on people who have a strong family history of melanoma, and is part of continuing efforts to identify the gene variants that contribute to melanoma risk. Most of the work described takes place as part of national and international collaborations to map and identify these melanoma susceptibility genes and to characterise their ef ....Melanoma is one of Australia s major cancer problems, but we still do not completely understand why certain people are at higher risk than others. This study is focussed on people who have a strong family history of melanoma, and is part of continuing efforts to identify the gene variants that contribute to melanoma risk. Most of the work described takes place as part of national and international collaborations to map and identify these melanoma susceptibility genes and to characterise their effects. Potential benefits from this research will be a better understanding of the place of genetic testing in assessing people s risk of melanoma, particularly if they have relatives with the disease, and way in which skin features like moles should be taken into account in that assessment. In addition, it is likely that better information about the genes altered in melanoma susceptibility and development will point to useful targets for development of novel anti-cancer agents.Read moreRead less
Understanding The Factors Governing Susceptibility And Outcome In Childhood Infection
Funder
National Health and Medical Research Council
Funding Amount
$276,122.00
Summary
This research seeks to understand why a minority of children are prone to severe and often life-threatening infections and inflammation. It focusses on infections both in preterm infants and in later childhood, which may also be relevant to understanding atherosclerosis. I am also interested in improving the health of recently arrived refugees, by conducting research that allows the development of evidence-based health interventions and developing national policy on refugee health.