Transcriptome Characterization Of Klebsiella Pneumoniae During Infection (TRACKIN)
Funder
National Health and Medical Research Council
Funding Amount
$348,806.00
Summary
Klebsiella pneumoniae (KP) is an important pathogen associated with high mortality and antimicrobial resistance. Upon infection, the host activates a sophisticated immune response, but there is evidence that KP is capable of modifying this response. Here I will take advantage of cutting-edge genome sequencing to understand the interactions between KP and host immunity. These studies will provide a pathway for the development of new therapeutic strategies to combat multiresistant infections.
Factors That Influence Disease Severity In Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$149,076.00
Summary
Tuberculosis (TB) is a major global health problem and is one of the leading causes of death from an infectious disease worldwide. The severity of disease that occurs with TB is dependent on many complex factors including the infected person’s immune system and factors related to the TB organism itself. This research will determine the key factors that cause severe disease in TB which will translate into improved care of TB patients and enhance further research in this field.
Characterisation Of Extracellular DNases Of Pseudomonas Aeruginosa And Their Contribution To Disease
Funder
National Health and Medical Research Council
Funding Amount
$418,516.00
Summary
The bacterium Pseudomonas aeruginosa causes a number of serious diseases of humans particularly of immunocompromised patients. We have found that this bacterium secretes enzymes that have the ability to digest DNA. This proposal aims to work out how this bacterium uses these enzymes to infect human tissues and escape killing by immune cells. The results from this study will help to determine if these proteins may be used as targets for the development of new anti-infective drugs.
Structural Characterization Of Novel AB5 Cytotoxin - SubAB
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
AB5 toxins are virulence factors from a range of pathogenic bacteria, including Shiga toxigenic E. coli (STEC), S. dysenteriae, V. cholerae, and B. pertussis. AB5 toxins comprise a catalytic A subunit that disrupts distinct essential cellular processes within the cell and a receptor binding, pentameric B subunit that enables the toxin to target certain cell types. We are structural characterizing a novel AB5 toxin that targets an essential component of the cellular machinery.
The Role Of Subgenomic Non-coding Viral RNA In Flavivirus Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Flaviviruses are transmitted by insects and pose a serious health threat to the Australian population. They can cause fever syndromes, encephalitis and death. We aim at better understanding of how these viruses cause disease. We are particularly interested in elucidating the role of small non-coding nucleic acid produced by flaviviruses in the viral pathogenicity. Ultimately, this deeper understanding should lead to the development of effective vaccines and antiviral therapies.
Modulation Of Leishmaniasis By The Proinflammatory Cytokines TNF
Funder
National Health and Medical Research Council
Funding Amount
$288,911.00
Summary
We have established a mouse model that has been genetically modified and cannot produce the cytokine tumour necrosis factor. This cytokine is secreted in the beginning of the inflammatory response. If these mice are infected with a parasite they are not able to heal the infection and die quickly. We can demonstrate that these mice cannot regulate the beginning inflammatory response and do not form a cellular infiltrate at the site of infection.
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.
We seek to gain a detailed understanding of how interactions between the West Nile virus proteins and host factors involved in the IFN response determine the outcome of virus infection. Better understanding of the mechanisms employed by this highly pathogenic virus to disable the mammalian host's IFN response will have wider implications for our understanding of other human diseases such as cancer, autoimmunity and provide new avenues for design of efficient antiviral and anticancer therapies.
Scabies is caused by microscopic mites burrowing through the skin, causing intense itching and providing prime breeding sites for bacteria. The resulting skin sores are very common among Aboriginal children in Australia leading to extreme levels of rheumatic fever-heart disease and renal failure in Indigenous communities. We have discovered mite products termed Serpins which interfere with the patients defence against the mites and the bacteria and aim to develop therapeutics.