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
Tuberculosis is one of the most threatening infectious diseases worldwide due to the low efficiency of the only licensed anti-tuberculosis vaccine, BCG. This project aims to interrogate two previously neglected immune mechanisms and their potential to enhance vaccine-induced immunity by incorporating these mechanisms into new genetically modified BCG strains. We will also investigate alternative BCG vaccination routes to generate long-lived immune cells that can rapidly control the infection.
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
Vaccine Discovery For Human Mucosal Pathogens: Identifying Novel Vaccine Antigens That Are Stably Expressed During Host Interactions, Using Analysis Of Cell-contact And Phasevarion Mediated Expression Profiles
Funder
National Health and Medical Research Council
Funding Amount
$418,482.00
Summary
The control of several human pathogens depends on vaccine development due to antibiotic resistance and the devastating outcome of infection. This work aims to identify new vaccine targets for diseases including gonorrhoae, ear infections, meningitis and sepsis, based on proteins required for interaction with human cells. Proteins that are randomly switched on and off in these bacteria will also be studied to better understand disease and to rule out variably expressed genes from new vaccines.
Combating The Reemergence Of Tuberculosis With New Vaccine Strategies
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Tuberculosis is a major global public health problem with significant morbidity and mortality. This project aims to generate new, highly efficacious vaccination regimens against tuberculosis, especially pulmonary tuberculosis, which is the most difficult manifestation of the disease to control. The outcomes of this project have the potential to save millions of lives worldwide and to decrease socioeconomic burden of tuberculosis, particularly in the context of HIV co-infection.
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
Identification Of Novel Gonococcal Virulence Factors And Vaccine Antigens Based On Their Expression During Host Cell Contact And Their Role In Association, Invasion And Survival In Cervical Epithelia
Funder
National Health and Medical Research Council
Funding Amount
$371,922.00
Summary
The sexually transmitted infection gonorrhoea is a significant health problem worldwide. Control of gonorrhoea depends on the development of a vaccine due to the continuing increase of antibiotic resistance and the staggering outcomes of infection, including infertility and increased transmission of HIV. My research aims to discover new vaccine targets by identifying gonococcal proteins that are required for interaction with human cervical cells.
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.