Genetic And Biochemical Analysis Of The PIM/LAM Biosynthetic Pathway In Mycobacteria.
Funder
National Health and Medical Research Council
Funding Amount
$272,250.00
Summary
Tuberculosis (TB) is one of the most devastating diseases in human history. TB kills approximately two millions people each year worldwide, more than any other disease caused by a single infectious agent. The disease has re-emerged in recent years due to the AIDS epidemic and the appearance of TB bacteria that are not killed by currently available antibiotics. New antibiotics must be developed to combat this global health threat. This requires the identification of targets on the bacteria on whi ....Tuberculosis (TB) is one of the most devastating diseases in human history. TB kills approximately two millions people each year worldwide, more than any other disease caused by a single infectious agent. The disease has re-emerged in recent years due to the AIDS epidemic and the appearance of TB bacteria that are not killed by currently available antibiotics. New antibiotics must be developed to combat this global health threat. This requires the identification of targets on the bacteria on which antibiotics can act. One particularly attractive target is the outer coat of the bacterium. Several existing antibiotics target the bacterial coat, yet the ways in which coat is assembled are poorly understood. Two related compounds in the bacterial coat, and unique to TB bacteria, are called PIMs and LAMs. The structures of these compounds are known, and the compounds appear to be essential for the survival of the bacteria in the human host. However, the mechanisms by which PIMs and LAMs are made by the bacteria are very poorly understood. The aim of our research proposal is to better understand the process by which these compounds are made. If this process can be blocked by an antibiotic, then this represents a potential anti-TB therapy which could save millions of lives worldwide.Read moreRead less
SiRNA Induced TGS Of Retroviruses: Elucidation Of Underlying Mechanisms And Their Application In Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$371,502.00
Summary
AIMS To elucidate changes in DNA that accompany suppression of HIV growth caused by certain unusual RNA molecules that turn off the ability of HIV to reproduce and make the virus dormant within the infected cell. While we have discovered RNA molecules that can do this to HIV in the test tube, we wish to develop similar molecules that can be used in animal models, so that we can decide whether this technology can be developed for use in humans. We also wish to understand more clearlky the mechani ....AIMS To elucidate changes in DNA that accompany suppression of HIV growth caused by certain unusual RNA molecules that turn off the ability of HIV to reproduce and make the virus dormant within the infected cell. While we have discovered RNA molecules that can do this to HIV in the test tube, we wish to develop similar molecules that can be used in animal models, so that we can decide whether this technology can be developed for use in humans. We also wish to understand more clearlky the mechanisms underlying this effect. BACKGROUND These RNA molecules can suppress a range of pathogenic human viruses including HIV-1 in the test tube. Our novel approach appears to induce changes that are long lasting and are less susceptible to mutations by the virus that allow it to become resistant to other therapeutic strategies. RESEARCH PLAN Initially more work will be done in tissue culture to determine the optimal design of these molecules and the best way to administer them. The most promising of these designs will be tested in small groups of infected animals as a preliminary demonstration of efficacy. In parallel experiments will be performed to elucidate the mechanisms undelying the suppressive effects of these molecules. OUTCOMES AND SIGNIFICANCE This work will lead to a significant increase in our understanding of the way replication of HIV is regulated and will develop a promising new therapeutic strategy for this virus that may be applicable to other conditions.Read moreRead less
Integrons, Mobile Gene Cassettes And Pathogencity In Vibrio Cholerae
Funder
National Health and Medical Research Council
Funding Amount
$550,285.00
Summary
Bacteria are remarkably adaptive and evolve in ways that plants and animals do not. One of these ways is Lateral Gene Transfer or LGT, which is a process allowing bacterial cells to share genes. Such mobile genes can greatly influence the extent to which pathogenic bacteria can cause disease. One notable example is Vibrio cholerae where many strains can be benign but some can give rise to cholera pandemics. Here, we will investigate this phenomenon in this important bacterium.
Regulation Of Toxin Production In Clostridium Difficile
Funder
National Health and Medical Research Council
Funding Amount
$472,169.00
Summary
The research aims to determine how toxin production is controlled in an emerging bacterial pathogen that is a major cause of gastrointestinal infections in hospitals. We will determine the nature of the external signals and the mechanisms by which the bacterium uses those signals to regulate toxin production. These studies will significantly expand our knowledge of how this important bacterium causes disease, a key to developing new methods for the control and treatment of disease.
SiRNA Induced Transcriptional Silencing Of HIV-1: Elucidating The Mechanisms And Exploring Options For Delivery
Funder
National Health and Medical Research Council
Funding Amount
$512,631.00
Summary
Current drug therapy for HIV is for life We have discovered a set of molecules that will turn off the ability of HIV to reproduce itself. These molecules are from a new family of RNA molecules . A single dose of these molecules suppress the ability of the virus to reproduce itself for more than a month. Further we have found ways of extending this supressive ability to greater than one year. These studies will tell us how these molecules work and how they might be effectively administered.
Early Diagnosis And Prognosis Of Severe Dengue In Vietnamese Children
Funder
National Health and Medical Research Council
Funding Amount
$689,323.00
Summary
Dengue is a mosquito-borne viral infection. Tropical Australia has experienced multiple outbreaks of dengue in the last decade. This project, conducted in Ho Chi Minh City, Viet Nam, will define the accuracy of a rapid diagnostic test for the early diagnosis of severe dengue. In doing so, we will also derive an algorithm using simple laboratory and clinical findings that can help identify those patients at greatest risk of severe complications, with benefits for both patients and hospitals.
Understanding The Importance Of Panton-Valentine Leukocidin Production In Australian Isolates Of Staphylococcus Aureus.
Funder
National Health and Medical Research Council
Funding Amount
$118,796.00
Summary
New strains of the superbug methicillin-resistant Staphylococcus aureus (MRSA) have emerged in the community, causing severe, sometimes fatal infections in otherwise healthy people. These strains, called community-acquired MRSA produce a toxin (Panton-Valentine leukocidin). This project will provide important information about how this toxin promotes disease, and how the immune system responds to the toxin, providing the basis for the development of immunotherapies against this new superbug.
Functional And Structural Studies Of A Glycosyltransferase Essential For Complex Glycolipid Biosynthesis In Mycobacteria
Funder
National Health and Medical Research Council
Funding Amount
$508,838.00
Summary
Tuberculosis (TB) kills more than three 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.
A Functional And Structural Approach To Understanding Leptospiral Host-pathogen Interactions
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
Leptospirosis is a zoonosis of worldwide distribution caused by infection with pathogenic Leptospira. Infection occurs due to contact with water contaminated by urine of domestic animals. It occurs infrequently in Australia, but recent local surveillance data indicate hospitalisation rate of 56% with an average duration of 5.3 days. Through the combined approach of structural biology and functional microbiology we hope to understand how leptospira interacts with the human host.