Activation And Inhibition Of The Plasminogen/Plasmin System
Funder
National Health and Medical Research Council
Funding Amount
$800,663.00
Summary
Plasmin is crucial enzyme present in blood plasma that functions in clot dissolution, inflammation, tissue remodeling, and wound healing. We aim to study how this enzyme system is controlled, by studying its interaction with receptors, co-factors and inhibitors. The information we gain will help drive the development of new generation therapeutics for the fine control of plasmin function in clotting disease, bleeding and inflammation.
Optimising Intervention Strategies To Reduce The Burden Of Group A Streptococcus In Aboriginal Communities
Funder
National Health and Medical Research Council
Funding Amount
$856,896.00
Summary
Skin sores are highly prevalent in remote Australian Indigenous communities and can lead to invasive infections and rheumatic heart disease. We will develop mathematical models to understand the transmission of skin sores, allowing us to define the optimal extent (household, community, region), timing and triggers for interventions to interrupt transmission. This will guide public health policy in reducing the prevalence of skin sores and scabies, and their accompanying disease burden.
Group A Streptococcal Human Challenge Study: Accelerating Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$2,018,741.00
Summary
Infection with group A streptococcus (GAS) is a major cause of morbidity and mortality worldwide, including in the Aboriginal population of Australia. Concerted efforts for vaccine development have been hampered by the absence of a suitable animal model. To address this critical knowledge gap we propose to develop a controlled human infection model of GAS infection. This model will provide a direct pathway for the future appraisal of novel GAS vaccines.
The END RHD CRE: Developing An Endgame For Rheumatic Heart Disease In Australia
Funder
National Health and Medical Research Council
Funding Amount
$2,601,147.00
Summary
Rheumatic heart disease (RHD) is caused by an abnormal immune reaction to some bacterial infections. Although RHD is rare in developed countries, Indigenous Australians still live with the burden of RHD. The END RHD CRE will explore risk factors for RHD, prevention with antibiotics, management of RHD and the potential for vaccine development. Individuals and communities experiencing RHD are integral partners to this work. The CRE will establish a strategy for ending RHD in Australia.
Group A streptococcus (GAS) is a bacteria that causes a wide range of disease in humans. GAS diseases are more common in Australias Indigenous population, and other health and economically disadvantaged groups than more affluent groups. In this study we will evaluate the effectiveness of novel vaccine candidates designed to prevent infection from all strains of GAS.
Investigating The Antimicrobial Activity Of Zinc At The Host-pneumococcal Interface
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Streptococcus pneumoniae is a human-only bacterium that is responsible for killing more than one million people every year. This project will analyse how the human immune system fights this bacterium, and subsequently, how the bacteria manages to subvert these attacks and survive in the human host. This will provide crucial information for developing new drugs against this pathogen, in an attempt to combat the ever-increasing problem of antibiotic resistance.
PrtFII, A Streptococcus Pyogenes Fibronectin Binding Protein, And Invasive Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$296,540.00
Summary
Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin bind ....Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin binding protein, than those from uncomplicated skin sores. In this application we propose to extend this observation and compare biochemical properties of PrtFII from strains belonging to the above two sets of collections. We hypothesise that PrtFII from invasive strains bind to fibronectin more tightly than the proteins from strains that cause uncomplicated infection. We also will test whether sera from invasive disease cases have lower titre of antibodies to the conserved region of PrtFII than sera from uncomplicated cases. A streptococcal vaccine by necessity has to be a multi-component vaccine to cover a wide spectrum of diseases and epidemiological differences. The study proposed here may provide a basis to argue whether or not to include PrtFII in such a multi-component vaccine.Read moreRead less
Dissemination And Virulence Properties Of The She Pathogenicity Island Of Shigella Flexneri.
Funder
National Health and Medical Research Council
Funding Amount
$110,625.00
Summary
Bacterial species belonging to the genus Shigella are responsible for intestinal diseases ranging from mild diarrhoea to life threatening bacillary dysentery. Such diseases kill over a million people, mainly infants in developing countries, every year and lead to serious morbidity and mortality even in industrialised countries with well developed health care systems. In many cases the virulence of Shigella species is augmented by large fragments of DNA, called pathogenicity islands, that carry g ....Bacterial species belonging to the genus Shigella are responsible for intestinal diseases ranging from mild diarrhoea to life threatening bacillary dysentery. Such diseases kill over a million people, mainly infants in developing countries, every year and lead to serious morbidity and mortality even in industrialised countries with well developed health care systems. In many cases the virulence of Shigella species is augmented by large fragments of DNA, called pathogenicity islands, that carry genes which contribute to the development of disease (pathogenesis) in humans. Pathogenicity islands are important genetic elements which appear to spread independantly throughout bacterial populations and therefore contribute to the emergence of new virulence traits in bacteria. Recently, we identified two related pathogenicity islands carried by both Shigella flexneri and other species of the genus Shigella. The two pathogenicity islands belong to a unique class of genetic elements found in Shigella species and virulent strains of the intestinal bacterium E. coli. Our current study is aimed at (1) understanding the mechanisms by which one of these islands, the she pathogenicity island, spreads from one bacterial strain to another to introduce disease-producing or virulence genes to new bacteria and (2) to study how the sigA virulence gene, carried on the she pathogenicity island, contributes to disease development in humans. We know that sigA encodes a protein toxin which contributes to the loss of fluid from the intestines of rabbits that have been experimentally infected with Shigella flexneri. We propose to study the structure and function of the SigA protein to determine how it interacts with tissues to produce a pathological state. Such studies will enhance our understanding of the process of disease development and contribute to the investigation and assessment of new strategies for therapeutic intervention.Read moreRead less