THE ROLE OF A NOVEL HYALURONIDASE IN THE TURNOVER OF CHONDROITIN SULPHATE GLYCOSAMINOGLYCANS IN CARTILAGE AND BONE
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
The degradation of complex carbohydrate structures occurs within specialised intracellular organelles (lysosomes). Their degradation occurs in a strictly defined sequence involving initial clipping into intermediate sized fragments which are each then degraded piece by piece from one end. In this proposal we seek to understand the role of a newly defined enzyme in the initial clipping process. This information will aid our understanding of skeletal pathology in a group of genetic disorders in wh ....The degradation of complex carbohydrate structures occurs within specialised intracellular organelles (lysosomes). Their degradation occurs in a strictly defined sequence involving initial clipping into intermediate sized fragments which are each then degraded piece by piece from one end. In this proposal we seek to understand the role of a newly defined enzyme in the initial clipping process. This information will aid our understanding of skeletal pathology in a group of genetic disorders in which complex carbohydrate degradation is impaired. In addition due to the widespread location of complex carbohydrates and their fundamental roles in tissue development and growth, the project has wider implications in diverse disease states such as cancer and wound repair.Read moreRead less
Genotypes And Phenotypes Of Human Primary Non-congenital Antibody Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$544,692.00
Summary
Antibodies represent a key component of the immune system, and a particularly important in defence against bacterial and viral infections. In some individuals, antibody production fails, rendering them more susceptible to infection. In most cases, the mechanism of antibody failure is unknown. This project seeks to determine the genetic and cellular mechanisms of antibody failure. This could improve diagnosis for immune deficiency, and improve our overall understanding of the immune system.
Understanding Skeletal Development: A Non-proteolytic Mechanism Of Aggrecan Resorption In The Growth Plate
Funder
National Health and Medical Research Council
Funding Amount
$563,044.00
Summary
Bone formation requires resorption of a cartilage template. We challenge the dogma that cartilage resorption is only by PROTEASES, and propose instead that GLYCOSIDASES might also be involved. Aims: Demonstrate that chondrocytes release glycosidases that are important for bone formation. Significance: New information for the design of reconstructive therapies for people with congenital and acquired limb deficiencies or inherited disorders such as arthritis and chondrodysplasias may be gained.
Secretion is an essential step in memory and learning, control of metabolism and reproduction and the functioning of most organs. Secretory dysfunction also underlies many diseases including type 2 diabetes. We plan experiments to test for a new model of control of insulin secretion.
Role For Zinc And ZIP2 In The Action Of Nitric Oxide And In Vascular Protection Against Cigarette Smoke And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$685,941.00
Summary
The NO/cGMP signalling pathway, which is central to cardiovascular physiology and protection against disease, is only fully effective when there are adequate levels of zinc in the vascular endothelium. This is especially important where zinc stores are depleted (elderly, smokers, diabetics and kidney disease). There is an urgent clinical need to implement strategies to monitor vascular Zn status. This application will explore the underlying science and translate these to the clinic.
Defining The Role Of Zinc At The Host-pneumococcal Interface
Funder
National Health and Medical Research Council
Funding Amount
$870,925.00
Summary
Streptococcus pneumoniae is the world’s foremost bacterial pathogen. In Australia, bacterial infections are responsible for more than 9000 deaths every year, and the economic burden associated with treating diseases arising from pneumococcal infections is more than $1 billion annually. This proposal aims to define the role of the transition metal zinc in innate immune resistance to bacterial infection. This knowledge will reveal new targets for next generation antimicrobial therapeutics.