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A Unique Network Of Phagocytic Cells At The Interface Between The Liver And Peritoneal Cavity
Funder
National Health and Medical Research Council
Funding Amount
$787,521.00
Summary
This project aims to characterise the nature and ontogeny of a novel population of cells with phagocytic capacity that forms a network underlying the capsule of mouse and human liver reminiscent of that formed by Langherans cells in the epidermis of the skin. In this project we will characterise this newly described liver capsular macrophage subset, define their ontogeny and assess their specific functions.
Discovery Of New Tuberculosis Drug Leads Targeting Cell Wall Biosynthesis
Funder
National Health and Medical Research Council
Funding Amount
$714,816.00
Summary
There is a desperate need for the development of new therapies for the treatment of TB due to widespread resistance of Mycobacterium tuberculosis, the causative agent of TB, to current therapies. The overall goal of this research project is to identify new TB drug leads through the development of structural analogues of bacterially-derived natural products called the sansanmycins that inhibit cell wall synthesis in Mycobacterium tuberculosis.
The Emerging Problem Of Non-tuberculous Mycobacteria Infection: Understanding Aetiology, Geospatial Epidemiology And Developing Interventions
Funder
National Health and Medical Research Council
Funding Amount
$988,791.00
Summary
This project will be largest study of non-tuberculous mycobacterial (NTM) infection in cystic fibrosis. By combining growing the bacteria with detailed information from the CF patient data registry, geographical location and environmental conditions, this study will provide novel insights into factors associated with NTM. Gene sequencing and airway infection profiling will extend understanding and has the potential to identify novel risk factors and biomarkers for NTM-related airways disease.
A New Class Of Inhibitors For The Treatment Of Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$720,691.00
Summary
Tuberculosis (TB) remains a major cause of mortality and morbidity worldwide, with 1.3 million deaths annually. Some strains of the TB bacterium are resistant to all available drugs. We have identified novel chemical structures that display potent and specific activity against pathogenic mycobacteria. In this proposal we will develop optimised derivatives with more potent activity against mycobacteria, assess their stability and toxicity and determine their mode of action.
Mycobacterial Control Of The Establishment And Outcome Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$311,956.00
Summary
Tuberculosis (TB) claims almost two million lives every year. TB subverts host immunity by directing the immune cells to launch an ineffective response to infection. One such trick is to hijack control of a class of molecules called eicosanoids from the host. This project will use a validated zebrafish model of TB infection to pinpoint the mechanisms used by mycobacteria to subvert normal eicosanoid production. Findings from this work may to aid the creation of novel anti-TB therapies.
Buruli ulcer (BU) is a destructive skin and soft tissue infection that can cause permanent deformity. Australian native possums carry in their guts the bacteria that causes BU and mosquitoes spread BU to people from areas contaminated by possum faeces. A targeted intervention based on screening possum faeces followed by control of mosquitoes in areas where possums and mosquitoes are shown to carry the bacteria will be trialed here, giving public health officials a means to stop this disease.
Visualisation Of Gamma-delta T Cell Responses In Cutaneous Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$570,876.00
Summary
Mycobacterial infections remain a major burden of modern society. This proposal aims to define the role of an understudied immune cell subset, gamma-delta T cells, in the response against mycobacteria. We will use cutting-edge multi-photon imaging to track these cells in real-time directly within infected tissues. This will facilitate generating a new vista of anti-mycobacterial immune responses and may aid the development of improved vaccines.
Chronic Bacterial Infection And The Generation Of T Cell Memory: Implication For Vaccination Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Two million people die from tuberculosis (TB) each year. The immune system is unable to eradicate the TB bacterium, and the type of immune response needed to protect against the disease is poorly understood. We will use animal models of TB infection and sophisticated immunological techniques to decipher how the TB bacterium interacts with the immune sytem and causes disease. We will also develop new TB vaccines that aim to boost the immune response in the lung, the main site of TB infection.
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
Understanding The Biosynthesis Of Complex Polyketide Lipid Toxins In Pathogenic Mycobacteria
Funder
National Health and Medical Research Council
Funding Amount
$298,898.00
Summary
Some major infectious diseases such as tuberculosis are caused by bacteria that make very unusual lipids (fats) that can kill human cells or interfere with the human immune system. The aim of this project is to work out how bacteria make these lipids. This knowledge will open up new avenues for treatments to stop bacterial lipid production and prevent disease. There are also potential applications in harnessing the bacterial lipid machinery to make new drugs and a wide range of other chemicals.