Detecting Bioactivity In A Naturally-occurring Aggrecan Fragment
Funder
National Health and Medical Research Council
Funding Amount
$407,634.00
Summary
The dynamic balance of anabolic and catabolic processes in healthy cartilage is disturbed in arthritis, with increased catabolism leading to irreparable cartilage damage. We will study the ability of a naturally-occuring aggrecan fragment to modulate cartilage catabolism. Our in vitro and in vivo experiments suggest that the aggrecan fragment limits cartilage destruction. This study tests our hypothesis that the aggrecan fragment antagonises cartilage damage and promote cartilage repair.
Elastic Fibre-matrix Interactions Important For Tissue Development, Morphology And Function
Funder
National Health and Medical Research Council
Funding Amount
$376,980.00
Summary
The properties of many tissues are controlled by the type, ratio and organisation of structural proteins laid down into extracellular matrices. Molecular interactions between these different proteins are essential for normal tissue strength, form and function. We are investigating the interactions of protein components of elastic fibres, with structural molecules of the surrounding matrix including collagens, proteoglycans and basement membrane components. At present our knowledge of these inter ....The properties of many tissues are controlled by the type, ratio and organisation of structural proteins laid down into extracellular matrices. Molecular interactions between these different proteins are essential for normal tissue strength, form and function. We are investigating the interactions of protein components of elastic fibres, with structural molecules of the surrounding matrix including collagens, proteoglycans and basement membrane components. At present our knowledge of these interactions is limited even though they are essential for anchorage during stretching of elastic fibres in compliant tissues such as arterial walls, lung and skin. In addition several of the elastic fibre-associated proteins appear to be important in the matrix of non-elastic tissues such as bone and cornea. The project will continue to increase our fundamental understanding of the normal development and function of different connective tissues. This knowledge will, in turn, lead to much greater elucidation of the mechanisms leading to a) loss of tissue function in major disease processes such as atherosclerosis, blood vessel aneurysms, pulmonary emphysema and UV-induced skin damage, and b) developmental abnormalities in congenital disorders such as Marfan syndrome and a variety of corneal dystrophies.Read moreRead less
Interactions Between Advanced Glycation And Oxidative Stress In Diabetic Renal And Cardiac Complications
Funder
National Health and Medical Research Council
Funding Amount
$431,700.00
Summary
Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's a ....Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's ability to renew these protein, hence causing accelration of the ageing process. In fact, it is estimated that this process occurs almost fifty times faster in diabetes. These sticky complexes accumulate in tissues causing disruption ot the normal tissue structure. Our group has a drug which can act as scissors and cut the sticky sugar off the proteins allowing it to be turned over. Unfortunately this does not fix all of the damage. These AGE molecules are involved in a number of other harmful processes including the production of toxic oxygen derived molecules which are harmful byproducts of diabetes. While these oxygen 'radicals' have been implicated in heart attack and stroke their source has remained a mystery in diabetes. Previously, the only way to remove these molecules was to mop them up with antioxidants such as Vitamin E. Antioxidants work slowly and so some damage is already done before they 'detoxify' these oxygen radicals. We propose to use combinations of medicines to see if we can achieve more effective protection against these processes in experimental diabetes. This may provide new therapies for threatment of kidney and heart disease in diabetes.Read moreRead less
Function Of Matrix Proteins Important For Storage And Activation Of TGF And TGF -induced Tissue Remodelling And Repair
Funder
National Health and Medical Research Council
Funding Amount
$690,875.00
Summary
The growth factor TGF is important for tissue development and repair, and in diseases such as pulmonary fibrosis, glomerulonephritis, liver cirrhosis, keloid formation and cancers. This project focuses on 2 important matrix proteins first discovered by Dr Gibson, LTBP-2 and ig-h3, that modulate TGF storage and TGF -induced tissue remodelling . We will use knock out mouse and cell culture models to determine the function of these proteins in tissue development and repair, and in diseases.
Assembly Functions Of Respiratory Syncytial Virus Matrix Protein
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Respiratory syncytial virus (RSV) is the single most important cause of lower respiratory infections (pneumonia and bronchiolitis) in young infants. In addition to the morbidity of RSV infection itself, it is well established that symptomatic RSV infection in infancy predisposes to asthma later in life. As all infants are infected by RSV at least once by age 2 yrs, this virus represents a major public health problem. Additionally, re-infection by RSV is increasingly being recognized as a cause o ....Respiratory syncytial virus (RSV) is the single most important cause of lower respiratory infections (pneumonia and bronchiolitis) in young infants. In addition to the morbidity of RSV infection itself, it is well established that symptomatic RSV infection in infancy predisposes to asthma later in life. As all infants are infected by RSV at least once by age 2 yrs, this virus represents a major public health problem. Additionally, re-infection by RSV is increasingly being recognized as a cause of severe lower respiratory disease in the elderly and in immunocompromised patients. The goal of this research is to understand better the mechanisms used by RSV to replicate itself in mammalian cells. Information from this work could be used to design novel antiviral drugs to treat RSV, and novel attenuating mutations that may assist in developing live RSV vaccines. The research focuses on a key viral protein, the matrix (M) protein, which is involved in many steps in virus replication. We aim to understand how M protein interacts with other components of the virus (specifically, envelope proteins) to orchestrate virus assembly. To coordinate assembly of new virus particles, M protein binds to portions of virus envelope glycoproteins and to RSV nucleocapsids (the internal machinery of the virus), bringing them together at the cell membrane. The protein-protein interactions which are responsible for these functions of RSV M protein will be determined.Read moreRead less