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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
School-Age Outcomes Of Very Preterm Infants And Antenatal Magnesium Sulphate Therapy - A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$675,050.00
Summary
Despite recent major advances in care around the time of birth that have led to large increases in the survival rates for very preterm babies, the rate of adverse long-term health problems has not diminished in survivors, and remains too high compared with children not born very preterm. In particular they have higher rates of substantial problems with the way their brain works, particularly affecting their movement, vision, hearing, thinking and talking. We have just concluded a large clinical ....Despite recent major advances in care around the time of birth that have led to large increases in the survival rates for very preterm babies, the rate of adverse long-term health problems has not diminished in survivors, and remains too high compared with children not born very preterm. In particular they have higher rates of substantial problems with the way their brain works, particularly affecting their movement, vision, hearing, thinking and talking. We have just concluded a large clinical trial in Australia and New Zealand of magnesium sulphate which was given to mothers who were likely to deliver their baby too early (before 30 weeks of pregnancy). We have been able to show, for the first time, that magnesium sulphate was able to halve the rate of substantial problems with movement in 2 year old survivors, from 6% to 3%. However, we are not sure if this potentially important improvement will translate into better outcomes for the children as they grow older and reach school-age. As there are many examples of treatments given around the time of birth that have been shown to have some short-term benefits, but substantial long-term harms, we must be as certain as we can be that any advance in one small area of health is not counterbalanced by disadvantages in other health areas. We plan to assess the 1061 survivors from our earlier clinical trial of magnesium sulphate therapy at ages from 7-8 years, when they are at school. We will assess their movement and other important areas of their brain function, as well as their school progress and general health and growth. If we find important improvements in health at school-age of these children caused by magnesium sulphate therapy, without any substantial counterbalancing side-effects, magnesium sulphate will probably become standard therapy in mothers who are likely to deliver their baby very early. This will lead to a reduction in the burden of illness in the community caused by being born too early.Read moreRead less
TRAFFICKING OF MEMBRANE SULFATE TRANSPORTERS IN THE KIDNEY
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Many diseases such as diabetes, cystic fibrosis, Alzheimer's and Parkinson's, results from a defect in the intracellular trafficking of specific membrane proteins. One important family of membrane proteins are the renal sulphate transporters, NaSi-1 and sat-1. They are two important proteins that control body sulphate homeostasis. Sulphate in the body is essential for cell matrix formation and cartilage-bone development and growth. Trafficking defects in these proteins can lead to changes in ser ....Many diseases such as diabetes, cystic fibrosis, Alzheimer's and Parkinson's, results from a defect in the intracellular trafficking of specific membrane proteins. One important family of membrane proteins are the renal sulphate transporters, NaSi-1 and sat-1. They are two important proteins that control body sulphate homeostasis. Sulphate in the body is essential for cell matrix formation and cartilage-bone development and growth. Trafficking defects in these proteins can lead to changes in serum sulphate levels, which results in softening of the bones, insufficient cartilage development, and changes in many metabolic processes. Using techniques of molecular and cellular biology, we aim to identify the precise the mechanisms that control the trafficking of these proteins in cells. This will enable us to determine how these proteins functions in both the normal and diseased states, which is currently unknown.Read moreRead less