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.
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.
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.
Investigation Of The Role And Mode Of Action Of Mycolactones And Other Factors In The Pathogenesis Of Buruli Ulcer
Funder
National Health and Medical Research Council
Funding Amount
$509,267.00
Summary
Mycobacterium ulcerans is a bacterium that causes a very serious ulcerating skin disease known as Buruli ulcer. The only effective treatment is surgical removal of affected tissue, a process that can leave victims with life-long disabilities. Buruli ulcer has been increasing dramatically in many countries of Central and West Africa for reasons that are not well understood. Cases of Buruli ulcer also occur in the south and north of Australia where the disease is known as Bairnsdale ulcer and Dain ....Mycobacterium ulcerans is a bacterium that causes a very serious ulcerating skin disease known as Buruli ulcer. The only effective treatment is surgical removal of affected tissue, a process that can leave victims with life-long disabilities. Buruli ulcer has been increasing dramatically in many countries of Central and West Africa for reasons that are not well understood. Cases of Buruli ulcer also occur in the south and north of Australia where the disease is known as Bairnsdale ulcer and Daintree ulcer respectively. M. ulcerans produces an unusual toxin called mycolactone that kills human cells and causes immunosuppression. Mycolactone belongs to a class of compounds that have important pharmaceutical properties and include antibiotic, anti-tumour and immunosuppressive drugs. The aim of this project is to better understand how mycolactone kills cells and causes immunosuppression, and to identify other parts of M. ulcerans that may be required for ulcer formation. We have recently determined the complete DNA sequence of M. ulcerans and so we can now look very closely at how the bacterium causes disease. We will use our knowledge of the mycolactone DNA to genetically engineer modified mycolactones, and by systematically modifying mycolactone and then testing the properties of the modified compounds, we will be able to identify the components of mycolactone that confer its toxic and immunosuppressive properties. We will also test the products from other DNA sequences identified in M. ulcerans for their ability to kill cells or cause other biological effects that may be implicated in causing ulcers. The outcome of this project will be a much needed increase in our understanding of the role of mycolactone and other factors in causing Buruli ulcers. This knowledge will pave the way for developing effective treatments and will also open avenues for exploiting the biological properties of mycolactones in the development of new pharmaceuticals.Read moreRead less