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.
Investigating The Mechanisms Of Regulation Of Mycobacterial Cell Wall Biosynthesis
Funder
National Health and Medical Research Council
Funding Amount
$597,349.00
Summary
Tuberculosis (TB) kills around 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 involved in synthesis of the outer coat of the bacterium which are potential targets for new drugs for the treatment of this devastating disease.
Developing New Therapies To Combat Tuberculosis Through Inhibition Of Vitamin B5 Metabolism In The Organism That Causes The Disease
Funder
National Health and Medical Research Council
Funding Amount
$311,760.00
Summary
The metabolism of vitamin B5 by pathogenic microorganisms has been recognised as an attractive target for developing drugs to combat various infectious diseases. The aim of the proposed work is to develop inhibitors of vitamin B5 metabolism in the bacterium that causes tuberculosis, using a powerful, multidisciplinary approach known as “fragment-based drug discovery”. This work is likely to yield potent inhibitors of the target bacterium, which could ultimately be used to treat tuberculosis.
Molecular Epidemiology Of Mycobacterium Tuberculosis Infection In The Northern Territory, Australia
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
The Northern Territory (NT) of Australia has the highest jurisdiction-specific rates of tuberculosis (TB) in Australia, and TB is a disease that disproportionately affects Indigenous people. The factors that contribute to the spread of TB in the NT are incompletely understood. We plan to use technology known as “whole genome sequencing” of bacterial DNA to better the understanding of the spread of TB in the NT. This will help guide TB control policies.
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.
Inhibition Of Haemostasis As A Novel Host-directed Therapy For Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$528,471.00
Summary
Mycobacterium tuberculosis-induced vasculopathy is an important cause of stroke worldwide, and stroke is a common (~20%) complication of tuberculous meningitis, the most dangerous presentation of tuberculosis. Blood clotting may also speed the growth tuberculosis in the body further worsening the situation. We will use zebrafish find out if clotting can be targeted to slow the growth of mycobacteria and then translate our findings to a mouse model of pulmonary tuberculosis.
Multistage Vaccines For The Prevention Of Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$884,290.00
Summary
Almost two million people die from tuberculosis (TB) each year. The current vaccine, BCG, is ineffective at controlling TB and the type of immune response needed to protect against the disease is poorly understood. We have discovered new antigens of the TB bacterium, and we will combine them with novel delivery strategies to develop new TB vaccines. We will also determine the type of immune response needed to protect against TB, which will aid progression of vaccines into clinical trials.
Genes Of Mycobacterium Tuberculosis Essential For Latent Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
One third of the worlds population is latently infected with M. tuberculosis, the bacteria which causes TB. We have identified key genes in M. tuberculosis that enable the bacterium to shut-down and become latent. This project will investigate these genes, identify their role and yield vital information for a new paradigm of drug and vaccine development. Improved vaccines and drugs which can target and inhibit latency would be of enormous benefit to the global community.
Killing Infected Cells As A Mechanism To Eradicate Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$1,085,770.00
Summary
Mycobacterium tuberculosis (Mtb), the causative agent of TB, is rapidly becoming resistant to all antibiotics and this disease kills more than one million people each year. This underscores the urgent need to develop new treatments for this disease. We are developing a therapy that kills Mtb infected cells and may help to eradicate infection. This highly novel approach to the treatment of TB would have profound implications for the 2 billion people infected with this pathogen.