Role Of Hypoxia Inducible Factor In Innate Immune Function Against Gram-positive Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$241,352.00
Summary
Our society is currently facing the rise of drug-resistant pathogens ("superbugs") such as the potentially devastating methicillin-resistant Staphylococcus aureus, or _MRSA�. Recently, a molecule known as HIF has been shown to control the ability of our white blood cells to kill bacteria. This proposal aims to investigate the use of HIF boosting drugs to treat infections. These novel HIF agonists could be used alongside conventional antibiotics to improve infectious disease.
Iron, Pseudomonas Aeruginosa And Lung Disease In Cystic Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$322,875.00
Summary
Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to inc ....Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to increase the understanding of how P. aeruginosa persists in the CF lung, with the goal of developing more effective therapeutic strategies to eliminate chronic infection with this bacterium. The new perception is that P. aeruginosa bacteria flourish in mucus with a low oxygen content within the CF lung and persist despite aggressive antibiotic therapy because they have adopted an antibiotic-resistant, biofilm mode of growth. This has opened up exciting directions for new therapeutic strategies. Factors in CF mucus that regulate this mode of bacterial growth are potential targets for intervention. Our past work has shown that iron is likely to be one such factor. In this study, we will extend these findings and determine whether using iron-binding chemicals can disrupt these biofims and allow the host immune system and antibiotics to work more efficiently to kill the bacteria. Not only will this study provide further insights into the pathogenesis of P. aeruginosa in CF and the role of iron, but ultimately it will contribute to the improved treatment and prevention of chronic infection with this organism.Read moreRead less
Impact Of Influenza A Infection On T Cell-mediated Immunity To Pulmonary Tuberculosis.
Funder
National Health and Medical Research Council
Funding Amount
$488,058.00
Summary
Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of B ....Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of BCG.Read moreRead less
Understanding The Complex Relationship Between Host, Pathogen And Antibiotic Factors On Treatment Outcome In Serious Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$380,945.00
Summary
Millions of people still die every year from bacterial infections despite the availability of antibiotics. The same bacterial infection in one person can behave very differently in another person, so infections can range from trivial to life-threatening or fatal. Understanding the relationship between the patient, the infecting bacteria and the antibiotic treatment given will ultimately help to predict and improve outcomes for patients with serious bacterial infections.
The Team brings together a unique grouping of people with backgrounds in molecular biology, medical microbiology, microbiology, marine ecology and immunology to tackle a significant health problem infections caused by bacteria. Using a novel approach, based on understanding how marine organisms specifically interfere with bacterial colonisation, the Team over the past seven years has identified a group of compounds that represent a novel group of antibiotics. Publications and patenting by the Te ....The Team brings together a unique grouping of people with backgrounds in molecular biology, medical microbiology, microbiology, marine ecology and immunology to tackle a significant health problem infections caused by bacteria. Using a novel approach, based on understanding how marine organisms specifically interfere with bacterial colonisation, the Team over the past seven years has identified a group of compounds that represent a novel group of antibiotics. Publications and patenting by the Team has demonstrated that the Team is at the forefront of research in this area. The novel antibiotics work by preventing bacteria sticking to surfaces and by preventing the bacteria from releasing toxins. The studies will concentrate on those bacteria that produce infections in the lungs (acute pneumonia), eyes (corneal infection), ear (middle ear disease), and abscesses.Read moreRead less
Host-pathogen Interactions In Clostridial Myonecrosis
Funder
National Health and Medical Research Council
Funding Amount
$577,573.00
Summary
We will analyse the interaction between the bacteria that cause gas gangrene, and the infected host, from both a host and pathogen perspective. We will examine how the host’s response to infection can be modulated to decrease the severity of disease and we will identify the biochemical processes that are essential for bacterial growth in the host, a necessary prerequisite for disease. Outcomes will be a better understanding of the mechanisms of disease causation and improved disease control.
Manipulating Immunity To Mycobacterium Tuberculosis With Novel Vaccines And Immunotherapeutics
Funder
National Health and Medical Research Council
Funding Amount
$524,770.00
Summary
Tuberculosis (TB) is an enormous world health problem with 2 million deaths per year and an estimated one third of the world s population infected with the TB bacterium. People who become infected with the bacterium and cannot clear the infection are at great risk of developing TB later in life. Control of TB is confronted with two major problems. First, the only vaccine available for TB, known as BCG, is not very effective at preventing the disease. We do not know why BCG is not an effective va ....Tuberculosis (TB) is an enormous world health problem with 2 million deaths per year and an estimated one third of the world s population infected with the TB bacterium. People who become infected with the bacterium and cannot clear the infection are at great risk of developing TB later in life. Control of TB is confronted with two major problems. First, the only vaccine available for TB, known as BCG, is not very effective at preventing the disease. We do not know why BCG is not an effective vaccine and the type of immune response required to achieve optimal protection against TB is not fully understood. Second, the drugs currently used to treat TB are expensive, treatment times are long and drug resistance is increasing at an alarming rate. Therefore there is an urgent need to develop new vaccines and therapies against TB. We propose to use animal models of TB infection and sophisticated immunological techniques to compare immune responses generated by TB, BCG and new generation vaccines developed in our laboratory. This will allow us to identify the key features of a vaccine that results in effective, long-lasting protection against TB infection. Novel strategies to increase the immune response in the lung, the main site of TB infection, will also be examined. This will involve pulmonary delivery of molecules that increase the number and effectiveness of lung antigen presenting cells, which are necessary to drive the right type of immune response to eradicate the TB bacterium. Increasing lung immunity will be used to either boost the effect of the BCG vaccine, or as a therapy to kill the bacterium in those already infected. This is an internationally competitive project and our team is at the forefront of this research effort. The development of new vaccines to prevent TB or new strategies to treat established TB infection would be a major medical breakthrough and a represent a significant achievement for Australian health and medical research.Read moreRead less
Developing novel chemistries for removing environmental surface biofilms to reduce hospital acquired infections. This project will develop new detergents that more efficiently clean hospitals. This will increase hospital safety by decreasing infections, thus saving lives and healthcare costs.
Understanding heat shock protein complex vaccines. This project aims to understand the mechanism of action and formulation requirements of a novel vaccine technology that utilises heat shock protein complexes. By understanding how this technology works, future vaccines can be improved to induce the immune response required to target specific pathogens, as well as give assurance regarding its safety.