Metabolomic Analysis Of Leishmania Parasites; Identifying Metabolic Pathways Required For Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$605,963.00
Summary
Leishmania are single-celled parasites that target a major class of immune cell, affecting millions and killing thousands of people worldwide. We have developed new approaches for investigating how these parasites survive in the immune cells, and why different species of Leishmania cause markedly different pathologies. This information will be used to identify and validate new drug targets in these parasites.
The Role Of Fatty Acid Metabolism In Pathogenicity.
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Fungi which infect humans are a major health problem, especially for those with compromised immune systems (eg. AIDS, transplant and cancer patients). Pathogenic fungi must evade the host s immune system whilst deriving nutrients for growth. Some fungi evade the immune system by residing within host cells. This poses significant challenges to growth due to the nutrient poor environment. By understanding how these fungi adapt to growth inside host cells, new avenues for treatment will emerge.
Design, Development And Analysis Of New Tuberculosis Drugs
Funder
National Health and Medical Research Council
Funding Amount
$736,628.00
Summary
Serious issues of drug resistance have emerged in tuberculosis prevention and are placing enormous pressure on global health systems. We have identified an enzyme of M. tuberculosis that is essential for its survival. This project will develop potent inhibitory compounds for this enzyme. Further, we will identify new drug targets through a screen to specifically identify the genes of the organism essential for its survival in the body. This information will be used to develop new TB drugs.
Copper And Its Antibacterial Action: An Emerging Aspect Of Host Defence Against Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$454,858.00
Summary
This project will determine the way in which copper is used as an antimicrobial agent to kill Salmonella that reside inside the macrophage (white blood cell) of the host and also determine how Salmonella defends against copper-dependent killing. It will also determine the role of copper in the killing of extra-intestinal pathogens during sepsis. These results will provide information that can be used to manage and control infections intracellular and extracellular bacterial pathogens.
The Role Of The Intracellular Pathogen-recognition Molecule Nod1 In The Host Response To Helicobacter Pylori Infection.
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
The report in 1982 by two Australian clinicians, Drs Marshall and Warren, of a link between a spiral-shaped bacterium, Helicobacter pylori, and stomach disease in humans was to prove one of the ground breaking discoveries of medical research in the last 20-30 years. Despite extensive studies since, including the sequencing of the entire genomes of two different H. pylori isolates, many issues relating to H. pylori disease remain unanswered. For instance, it is still not known why all infected in ....The report in 1982 by two Australian clinicians, Drs Marshall and Warren, of a link between a spiral-shaped bacterium, Helicobacter pylori, and stomach disease in humans was to prove one of the ground breaking discoveries of medical research in the last 20-30 years. Despite extensive studies since, including the sequencing of the entire genomes of two different H. pylori isolates, many issues relating to H. pylori disease remain unanswered. For instance, it is still not known why all infected individuals develop inflammation of the stomach lining, yet only a proportion (15-20%) will go on to develop severe diseases, such as peptic ulcer disease and stomach cancer. Recent work from our groups has identified the mechanism by which H. pylori induces host responses in the cells lining the stomach, the epithelial cell. The interaction of the bacterium with these cells represents its first contact with the host, and sets the scene for the development of immune responses in the stomach. From their position on the outside surfaces of epithelial cells, certain strains of H. pylori are able to deliver a bacterial component into host cells, thus triggering an inflammatory response in the latter. Curiously, a host molecule called Nod1, which is present on the inside of cells and not on the surface, acts as an internal sensor by interpreting the entry of this H. pylori component as a danger signal for the host. The aim of the project will be to characterise the resulting defence mechanisms that are induced by Nod1 in order to prevent the colonisation of the stomach by H. pylori bacteria. It is expected that this work will address questions concerning the role of host immune defence mechanisms in H. pylori infection and stomach disease. Amongst the possible public health benefits of this work will be the development of novel therapies to reduce inflammation in the stomach by blocking Nod1 responses to H. pylori bacterial components.Read moreRead less
Investigating The Interface Between Host Innate Immune Cells And A Fungal Pathogen
Funder
National Health and Medical Research Council
Funding Amount
$578,085.00
Summary
Fungi which infect humans are a major health problem, especially for those with compromised immune systems (eg. AIDS, transplant and cancer patients). These fungi cause disease by evading the immune system whilst deriving nutrients for growth. Some fungi evade the immune system by residing within host cells; a hostile and nutrient poor environment. This project will study a pathway that we have shown is required for growth inside host cells. This knowledge will open new avenues for treatment.
Molecular Mechanisms Of Intracellular Growth, Survival And Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$335,816.00
Summary
Fungi which infect humans are a major health problem, especially for those with compromised immune systems (eg. AIDS, transplant and cancer patients). These fungi cause disease by evading the immune system whilst deriving nutrients for growth. Some fungi evade the immune system by residing within host cells; a hostile and nutrient poor environment. This project will study a pathway that we have shown is required for growth inside host cells. This knowledge will open new avenues for treatment.
Virulence Mechanisms In Hypervirulent Epidemic Strains Of Clostridium Difficile.
Funder
National Health and Medical Research Council
Funding Amount
$499,135.00
Summary
The bacterium Clostridium difficile is the major cause of nosocomial diarrhoea in many countries, including Australia. More virulent isolates have emerged since 2000, leading to increased incidence and severity of disease in many countries and resulting in epidemics. This project will make a major contribution to our understanding of how these bacteria cause disease and may help to prevent outbreaks of the hypervirulent strains in Australia by identifying potential new vaccine candidates.
Characterisation Of Enterohaemorrhagic Escherichia Coli Lacking Classical Virulence Markers
Funder
National Health and Medical Research Council
Funding Amount
$140,660.00
Summary
Some intestinal infections with the intestinal bacterium, E. coli, can result in severe, often fatal, kidney disease called the haemolytic uraemic syndrome. It is important for the diagnosis and treatment of this condition that the infections are detected swiftly. Current means of identifying this virulent form of E. coli are inadequate and do not account for all types of the bacteria that can cause severe disease. Children are particularly susceptible to life threatening infections with this ty ....Some intestinal infections with the intestinal bacterium, E. coli, can result in severe, often fatal, kidney disease called the haemolytic uraemic syndrome. It is important for the diagnosis and treatment of this condition that the infections are detected swiftly. Current means of identifying this virulent form of E. coli are inadequate and do not account for all types of the bacteria that can cause severe disease. Children are particularly susceptible to life threatening infections with this type of E.coli and usually acquire the infection by consuming contaminated food or water. This organism is currently a global food safety problem and the bacteria are especially prevalent in ground beef products and water or vegetables that have been contaminated with cattle faeces. In this study we aim to identify new bacterial genes and proteins that may be used to improve current means of detecting and diagnosing this kind of E.coli. A great deal is known about the way in which the classical strains of this virulent E .coli colonise the intestine however a small but significant group of these organisms do not carry known colonisation factors. We aim to identify bacterial proteins in these non-classical strains of E.coli which are needed for attachment of the bacteria to the host. Identifying how these bacteria interact with the host may help us to develop improved means of detecting and diagnosing this life-threatening infection.Read moreRead less
The Pathogenesis Of Infections Caused By Clostridium Sordellii.
Funder
National Health and Medical Research Council
Funding Amount
$400,232.00
Summary
The bacterium Clostridium sordellii causes necrosis and multiorgan failure with a very high mortality rate of 70% in infections of drug users, transplant and post-abortion patients, and 100% for post-partum patients. Little is known about how C. sordellii causes such devastating disease; treatment of these infections is currently ineffective. This project will make a major contribution to our understanding of how disease is caused and may lead to improved prevention and treatment stratetegies.