Determination Of Disease Specific Epitopes In Rheumatic Heart Disease In Australia
Funder
National Health and Medical Research Council
Funding Amount
$374,817.00
Summary
Rheumatic Fever and Rheumatic Heart Disease (RF-RHD) remain a significant cause of illness in Aboriginal communities in Australia. RF-RHD is a complication which follows infection with a specific bacterium. The purpose of this study is to compare the body's response and find out the patterns of antibody and immune cell reactivity to the bacterium and body proteins in RF-RHD patients and controls. It will also enable us to study the mechanisms that initiate the disease process.
Can Skin Infection With Group A Streptococcus Cause Acute Rheumatic Fever?
Funder
National Health and Medical Research Council
Funding Amount
$459,450.00
Summary
It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of ....It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of the cause of ARF, and have important implications for prevention of ARF around the world. Presently, these approaches focus on diagnosing and treating sore throat, but no country has proven that such a program can be successful in substantially reducing new cases of ARF. If it was known that skin infection could lead to ARF, then countries (including Australia) could emphasise the importance of skin health programs. A further benefit of this knowledge would be to influence GAS vaccine development, which presently is largely focused on the prevention of sore throat. A different possibility has recently been raised - that the cause of ARF may not always be GAS, but instead that the related bacteria GCS and GGS may have the potential to cause this disease. Proof of this hypothesis would even more dramatically alter our understanding of disease causation, prevention, and vaccine development. We propose to determine the cause of ARF in Aboriginal communities by regularly swabbing families of people with a history of ARF, and using genetic fingerprinting of the bacteria from the skin and throat swabs. When cases of ARF occur, we will be able to determine the site and type of infection that precipitated the attack. We will conduct a related study in more communities, in which we will swab family members of people with ARF and of control families (without ARF) to determine the bacteria most commonly isolated from ARF families.Read moreRead less
A Dual Antigen Synthetic Peptide Subunit Vaccine Approach To Prevent Streptococcal Associated Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$604,017.00
Summary
Infection with streptococcus is responsible for causing more than 500,000 deaths each year, the majority of which are due to rheumatic fever and rheumatic heart disease, which contributes to cardiovascular disease. Our research is aimed at the development of a vaccine to prevent heart disease and involves targeting multiple molecules present on the bacterial surface. We will use a novel vaccine delivery system developed in the laboratory, which will enable the vaccine to be delivered nasally.
There is an ongoing need for the development of new anticancer drugs, particularly those directed against solid tumours. In the past plants have been an extremely valuable source of anticancer agents, including the world s best selling anticancer drug, Taxol, isolated from the Pacific Yew tree. However, such molecules are typically complex and often very expensive to manufacture or extract from natural sources. So far very little attention has been paid to protein-based molecules from plants as ....There is an ongoing need for the development of new anticancer drugs, particularly those directed against solid tumours. In the past plants have been an extremely valuable source of anticancer agents, including the world s best selling anticancer drug, Taxol, isolated from the Pacific Yew tree. However, such molecules are typically complex and often very expensive to manufacture or extract from natural sources. So far very little attention has been paid to protein-based molecules from plants as potential anticancer agents because pharmaceutical companies have focused on organic molecules. In principle protein-based molecules could be produced much more cheaply and thus made available more widely to patients than existing drugs. All that is required are the lead molecules, or proteins that display sufficient anticancer activity to be used as the basis for further optimization. We have discovered a family of plant proteins called the cyclotides that have recently been shown to have considerable promise as anticancer agents. In the current project we will use synthetic chemistry to modify selected amino acids on the surface of this new family of proteins to determine which parts of the molecules are responsible for their activity. We will use this information to design improved analogues. The project is a collaboration between researchers at the Institute for Molecular Bioscience, University of Queensland, who have expertise in the required peptide chemistry and researchers and clinicians at Uppsala University, Sweden who have a range of assays and clinical expertise to test the new molecules. Both groups have been centrally involved in the discovery of the cyclotide family of plant proteins and are committed to developing them as exciting new anticancer agents.Read moreRead less
REGULATION OF GLUCOCORTICOID SENSITIVITY BY ANNEXIN-1
Funder
National Health and Medical Research Council
Funding Amount
$533,828.00
Summary
Steroids like prednisolone or cortisone are very effective at reducing inflammation in diseases like rheumatoid arthritis and are particularly known to decrease substances involved in inflammation. Almost 70% of patients with rheumatoid arthritis are treated more or less continuously with steroids. Steroid resistance (need for higher doses) or changes in steroid-sensitivity has been widely recognized in asthma, inflammatory bowel disease, and rheumatoid arthritis. Many new drug therapies however ....Steroids like prednisolone or cortisone are very effective at reducing inflammation in diseases like rheumatoid arthritis and are particularly known to decrease substances involved in inflammation. Almost 70% of patients with rheumatoid arthritis are treated more or less continuously with steroids. Steroid resistance (need for higher doses) or changes in steroid-sensitivity has been widely recognized in asthma, inflammatory bowel disease, and rheumatoid arthritis. Many new drug therapies however have the aim of keeping cortisone use to a minimum because of undesirable side effects like osteoporosis. Annexin-1 is an anti-inflammatory substance important in arthritis development which is also known to mediate many of the actions of steroids. However, the possible contribution of annexin-1 to mediate the effect of steroids in the regulation of these substances has not been examined. Moreover, how annexin-1 turns genes on is not known. Our studies will therefore reveal whether the absence of annexin-1 will increase inflammatory substances turn genes, and secondly, by determining the possible substances regulated by annexin-1 if the treatment with steroids are less effective in the absence of annexin-1. If annexin-1 is found either to increase anti-inflammatory substances or to mediate the effect of therapeutic steroids, its capacity to be involved in the beneficial effect of steroids may have an important impact in treatment of arthritis and other inflammatory diseases. If annexin-1 functionally acts as steroids, the reduction or discontinuation of steroid use will be possible.Read moreRead less