Understanding Virulence In Staphylococcus Aureus And Impacts On Host Response
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
Golden Staph remains an important cause of serious infections in Australian patients. New strategies to combat this disease require a better understanding of how Golden Staph causes disease and escapes the natural human response to infection. This study will provide new insights into how Golden Staph causes disease, and provide a platform for developing new strategies to prevent and treat Golden Staph infections.
Molecular Basis For The Emergence Of Community Acquired Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$427,518.00
Summary
Golden Staph is a major problem in our hospitals but serious Golden Staph infections are increasingly common in the community, among otherwise healthy people who have had no contact with hospitals. This project will find out how Golden Staph is evolving to become more likely to cause disease in the community. This knowledge can then be used to design new strategies for early detection, prevention and treatment.
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
Regulation Of Actin Polymerization During Malaria Parasite Invasion Of The Human Erythrocyte
Funder
National Health and Medical Research Council
Funding Amount
$318,147.00
Summary
Malaria parasites depend on successful invasion of red blood cells for their survival. Invasion is powered by a molecular motor based on two key proteins: actin and myosin. Non-specific drugs that inhibit parasite actin block invasion, demonstrating how important its regulation is to parasite success. This project will study several newly identified malaria actin-regulators, aiming to identify new drug targets that will block malaria actin function, stop motility and as such prevent disease.
Investigating Cytoskeletal Dynamics Across The Lifecycle Of The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$387,741.00
Summary
During its lifecycle the malaria parasite must cross tissues and invade cells in two very different hosts - humans and mosquitos. Although the molecules that drive this process are known, we know nothing about their dynamics in live parasites. Here, we will use state-of-the art microscopy and genetics to dissect parasite motility, tracking proteins in the parasite cell on their journey from human host through to the mosquito - utilising the first Australian malaria-dedicated insectary.
Mechanisms Underlying APOBEC3G Restriction Of HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
In the fight against worldwide HIV-AIDS, understanding natural cell defenses to the HIV virus may identify new virus targets and strategies to block HIV in humans. Here, we will use state-of-the-art, high resolution, fluorescent microscopy to understand how the recently identified cell protein, APOBEC3G, blocks the HIV life cycle in human cells. We anticipate that APOBEC3G will stop HIV from invading the nucleus of human cells to defend against HIV, a strategy we can apply to new therapies.
A Study Of The Molecular Epidemiology And Virulence Determinants Of Enterovirus 71 Strains From The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$286,325.00
Summary
In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to ....In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to poliomyelitis. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997, including a large epidemic in Perth, Western Australia in 1999. These epidemics have resulted in many deaths and cases of severe neurological disability. In view of the severity of EV71 neurological disease and the lack of effective treatments, our research effort needs to focus on prevention through public health surveillance and vaccine development. The major aims of our study are two-fold: 1. To study the origin and evolution of EV71 in the Asia-Pacific region using molecular techniques and to use this information to implement surveillance in Australia and Southeast Asia. It is anticipated that improved surveillance will provide early warning of impending epidemics. 2. To understand the molecular basis of virulence of EV71, with emphasis on the ability of virus to cause severe disease of the central nervous system. This study will have two goals: a. To identify the human cellular receptor of EV71. The ultimate goal of this research will be the development of a small animal model of EV71 encephalitis by constructing a transgenic mouse expressing the human cellular receptor for EV71. b. To construct an infectious cDNA clone of EV71 and to develop genetically defined attenuated strains by mutagenesis of the infectious clone. Mutant strains of EV71 will be tested for replication and virulence in newborn mice and in human neuroblastoma cells.Read moreRead less
The Role Of IL-18 In Proliferative And Crescentic Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$56,177.00
Summary
Inflammation of the small filters with the kidneys, known as glomerulonephritis, is the commonest cause of kidney failure in Australia. People whose kidneys have failed need either kidney dialysis or a kidney transplant. Our understanding of the immune events that cause glomerulonephritis is patchy. However, it is known that T cells are the directors of immune responses in the body and direct the immune response in glomerulonephritis. Chemical messengers known as cytokines direct the way T cells ....Inflammation of the small filters with the kidneys, known as glomerulonephritis, is the commonest cause of kidney failure in Australia. People whose kidneys have failed need either kidney dialysis or a kidney transplant. Our understanding of the immune events that cause glomerulonephritis is patchy. However, it is known that T cells are the directors of immune responses in the body and direct the immune response in glomerulonephritis. Chemical messengers known as cytokines direct the way T cells behave. One of these cytokines, known as interleukin-18, has been shown to stimulate T cells and other immune cells to induce inflammation that is helpful when the body is fighting infection but is harmful in immune diseases. This project will determine the role of interleukin-18 in glomerulonephritis by studying the way it talks to T cells and the mechanisms by which it incites inflammation in the kidney. Mice with glomerulonephritis will be treated by blocking the actions of interleukin-18 to discover whether interleukin-18 produced by the animal is important in kidney damage induced by glomerulonephritis, to understand the way in which this cytokine works and to assess whether blocking interleukin-18 could be a useful treatment for glomerulonephritis in humans. Current treatments for glomerulonephritis are often ineffective and have unwanted side effects. Knowledge of the way interleukin-18 participates in the immune response in glomerulonephritis may lead directly or indirectly to more effective and more targeted treatments for different forms of glomerulonephritis.Read moreRead less
Human Podocyte Depletion, Glomerular Hypertrophy And Glomerulosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$601,490.00
Summary
Many kidney diseases commence with injury to glomeruli (kidney filters) which leads to glomerular scarring and loss. There is strong evidence from animal studies that a specific glomerular cell type (the podocyte) is central to this process of glomerular injury. In this study, we will analyse the relationships between podocyte depletion and glomerular scarring in human kidneys from 5 racial groups (white and African Americans, white and Aboriginal Australians, Senegalese Africans).
A Population-based Family Study Of Filaggrin Mutations And Allergic Disease Risk In Australia
Funder
National Health and Medical Research Council
Funding Amount
$308,584.00
Summary
It is biologically plausible that the association of known environmental risk factors for asthma may be different for genetically susceptible individuals. Few studies have examined the interaction between genetic and environmental factors. that have not considered genetic susceptibility are estimating an average risk of asthma across all genotypes in the population which may not be relevant for a particular sub-group.