MECHANISMS AND MARKERS OF TUBERCULOSIS TRANSMISSION WITHIN AUSTRALIA
Funder
National Health and Medical Research Council
Funding Amount
$799,978.00
Summary
Tuberculosis (TB) kills nearly 2 million people each year. The emergence of drug resistant TB in the Asia-Pacific region poses a particular threat to Australia, due to frequent population mixing and ongoing TB transmission that may facilitate its spread within vulnerable communities. The proposed study will develop advanced tools to monitor and limit TB transmission within Australia. It will also provide novel insight into the evolution of the global TB epidemic and key factors that sustain it.
Regulation From The Outside: Control Of Transport And Assembly Of Major Cell Wall Components In Mycobacteria
Funder
National Health and Medical Research Council
Funding Amount
$652,019.00
Summary
Tuberculosis (TB) kills nearly two million people each year while the causative bacterial species, Mycobacterium tuberculosis, infects one-third of the entire human population. An alarmingly high rate of TB exists in Australia's indigenous population. This proposal aims to identify and characterise essential processes that regulate synthesis of the outer coat of the bacterium, which are potential targets for new drugs for the treatment of this devastating disease.
Targeting Redox Homeostasis To Prevent Mycobacterium Tuberculosis Persistence
Funder
National Health and Medical Research Council
Funding Amount
$396,025.00
Summary
Tuberculosis is now the leading cause of death from infectious disease worldwide. This reflects the ability of its causative agent to persist, leading to failure of antibiotic treatment and development of drug resistance. In this project, we propose to overcome this by inhibiting a unique metabolic pathway that is activated when the pathogen enters its persistent state. We will use a cutting-edge combination of techniques to develop this pathway for next-generation therapies.
Human Genetic Susceptibility To Pulmonary Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$760,432.00
Summary
Tuberculosis (TB) infects about a third of the world population, causing significant disease in 10% of infected individuals. We propose to undertake a genome-wide study to investigate human susceptibility to this devastating disease. Identifying novel gene associations from this study may explain why some people are more vulnerable to TB. Understanding these processes may lead to more effective treatments which is essential for the long term control of disease not only in China, but worldwide
RP105 Is A New Innate Immune Receptor For Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$525,583.00
Summary
Tuberculosis (TB) is a major global health threat that causes 1.7 million deaths every year. This study will characterise the interactions between the bacteria that cause TB and a new immune sensor. We found that this sensor is involved in controlling TB and this project will determine how it contributes to the immune defence against the infection. Such knowledge will help improve patient management and develop an effective vaccine and better treatments for this devastating disease.
Innate Immune Signalling In Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$562,857.00
Summary
Tuberculosis (TB) is a major global health threat that causes 1.5 million deaths every year. This study will characterise a new molecular control mechanism that optimises the immune response to the bacteria that cause TB and determine how it contributes to controlling the infection. Such knowledge is essential to help improve patient management and develop better treatments for this devastating disease.
Ketol-acid Reductoisomerase: An Important Antituberculosis Drug Target
Funder
National Health and Medical Research Council
Funding Amount
$690,113.00
Summary
Due to the increasing prevalence of drug resistance, new antituberculosis medications are urgently needed. Here, we will use rational structure-based approaches to design new inhibitors of ketolacid reductoisomerase (KARI), an enzyme whose activity is essential to the survival of this pathogen that resides in the lungs of humans. These inhibitors will be converted into prodrug formulations for optimal activity in cell-based assays and in mice infected with this pathogen.
Preventing The Evolution Of Transmissible Nitroimidazole Resistance In Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$664,463.00
Summary
Tuberculosis kills more people than any other infectious disease. Unfortunately, the drugs available to us to treat TB are losing their efficacy due to the evolution of drug resistance. A new class of drugs, nitroimidazoles, has been developed, but there is a risk that the bacterium that causes TB will develop resistance to these compounds too. We will identify resistance mutations before they occur in the wild, to help identify them and find new compounds for which resistance cannot develop.
Novel TB Drug Candidates Via The Inhibition Of Lipid I Biosynthesis
Funder
National Health and Medical Research Council
Funding Amount
$780,743.00
Summary
Tuberculosis (TB) is an enormous global health problem with a continuing impact in Australia. TB is now the leading killer of any infectious disease (1.8 million people per year) and the rapid emergence of drug resistant TB infections threatens to prevent efforts to control the disease. This project seeks to develop novel TB drug candidates that operate by preventing the construction of the cell wall by the bacterial agent that causes the disease.
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.