Discovering genes which modify human physical performance: a means of developing healthier life styles & novel athletic training programs. The aim of this multicentred study (University of Sydney, Australian National University, Australian Institute of Sport) is to find genes in the cardiac and musculoskeletal systems that are involved in modifying human physical performance. From this knowledge, it is proposed to develop novel physical training programs in our national sporting institutions ba ....Discovering genes which modify human physical performance: a means of developing healthier life styles & novel athletic training programs. The aim of this multicentred study (University of Sydney, Australian National University, Australian Institute of Sport) is to find genes in the cardiac and musculoskeletal systems that are involved in modifying human physical performance. From this knowledge, it is proposed to develop novel physical training programs in our national sporting institutions based on an individual's genetic information. In the broader community, knowledge of genes which contribute to the normal and healthy functioning of the cardiac and musculoskeletal systems will be invaluable in understanding and preventing breakdowns in these body systems.Read moreRead less
The Downstream Targets Of Patched/Hedgehog Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$423,055.00
Summary
The patched-hedgehog gene pathway is disturbed in common human cancer, including basal cell carcinoma of the skin, medulloblastoma, rhabdomyosarcoma and ovarian fibroma. This application proposes to look at the genes turned off and on by the patched gene. By identifying these genes and examining their function we will identify the exact genetic disturbance which results in a large proportion of common human cancer. Once we find these genes this opens up the possibilities of designing drugs which ....The patched-hedgehog gene pathway is disturbed in common human cancer, including basal cell carcinoma of the skin, medulloblastoma, rhabdomyosarcoma and ovarian fibroma. This application proposes to look at the genes turned off and on by the patched gene. By identifying these genes and examining their function we will identify the exact genetic disturbance which results in a large proportion of common human cancer. Once we find these genes this opens up the possibilities of designing drugs which specifically block the action of the geneticdefect and thereby treating the tumours.Read moreRead less
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
QTL Linkage Analysis For Complex Human Traits In Twin Families
Funder
National Health and Medical Research Council
Funding Amount
$1,000,000.00
Summary
This project will focus on finding genes for common human diseases. Now that the human genome has been sequenced, the race is on to find out what the estimated 38,000 human genes do and which ones are associated with which diseases. Scattered throughout the genome are small variations in DNA sequence, some of which increase the odds of disease while others are protective.
The Influence Of Alpha Actinins On Human Performance In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$480,989.00
Summary
We have identified a common genetic variation that results in absence of the fast muscle fibre protein, a-actinin-3, in over 1 billion people worldwide. Loss of a-actinin-3 influences elite athletic performance and skeletal muscle function in the general population by altering efficiency of muscle metabolism. We will now study mice and humans to determine how a-actinin-3 deficiency influences normal muscle function with age, response to exercise and the severity of human muscle disease.
A genomic and phenomic investigation of a mitochondrial glutathione transferase. The aim of this study is to understand of the genomics, structure and function of glutathione transferase Kappa (GSTK), a novel GST found in mitochondria. The investigations will achieve several outcomes. (1)an understanding of the organisation of GSTK gene(s) in humans and mice; (2) determination of the role of GSTK in mitochondria, by investigating the phenotype of knockout mice; (3) determination of the crysta ....A genomic and phenomic investigation of a mitochondrial glutathione transferase. The aim of this study is to understand of the genomics, structure and function of glutathione transferase Kappa (GSTK), a novel GST found in mitochondria. The investigations will achieve several outcomes. (1)an understanding of the organisation of GSTK gene(s) in humans and mice; (2) determination of the role of GSTK in mitochondria, by investigating the phenotype of knockout mice; (3) determination of the crystal structure of human GSTK; (4) An understanding of GSTK's substrate specificity, reaction kinetics and structure/function relationships. Since GSTK is confined to mitochondria, and may not be related to other GSTs, we may also identify novel functionsRead moreRead less
Epigenetic Hyperglycemic Cell Memory Causes Vascular Complications In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$332,140.00
Summary
This project seeks to identify how epigenetic change in response to hyperglycemia can cause vascular complications of diabetes, and how this contributes to “hyperglycemic memory”; a phenomena where cells may undergo gene modifications which increase risk to further complications later in a patients life. These studies are the first of their kind and will characterize the types of epigenetic change that can cause human disease.
Genome-wide Association Studies Of Biomedical Traits And Endophenotypes For Complex Disease
Funder
National Health and Medical Research Council
Funding Amount
$295,804.00
Summary
The burden of common complex diseases, such as cardiovascular disease is substantial to the health care system. These diseases are caused by genes and environments as well as their interactions. The proposed project will identify genes affecting the susceptibility of individuals to complex diseases. Discovery of such genes will be important for their diagnosis, prevention and treatment and may serve as an important resource for future personalized medicine.
Mechanisms of zinc transport and homeostasis in plants. Zinc deficiency is a widespread factor limiting crop production and affects many soils of southern Australia and around the world. Genetic techniques can be used to identify zinc-efficient crop breeds able to grow well under zinc deficient conditions and able to efficiently deliver zinc to cereal grains to alleviate nutritional zinc-deficiency in humans. This project will identify new genes important in zinc transport and homeostasis in pla ....Mechanisms of zinc transport and homeostasis in plants. Zinc deficiency is a widespread factor limiting crop production and affects many soils of southern Australia and around the world. Genetic techniques can be used to identify zinc-efficient crop breeds able to grow well under zinc deficient conditions and able to efficiently deliver zinc to cereal grains to alleviate nutritional zinc-deficiency in humans. This project will identify new genes important in zinc transport and homeostasis in plants and will ultimately allow their role in zinc efficient crops to be assessed. This will contribute to more rapid and directed strategies in breeding zinc efficient crops.Read moreRead less