Investigations Into The Mechanism Of Vaccine- Induced Protection Against The Gastric Pathogen Helicobacter Pylori.
Funder
National Health and Medical Research Council
Funding Amount
$276,000.00
Summary
Helicobacter pylori (H. pylori) is the most common gastro-intestinal pathogen worldwide and infects up to 20 % of the Australian population. Infection is thought to be acquired in childhood, and may cause acute or chronic gastritis, and gastric ulcer later in life. H. pylori infection is also strongly associated with the development of gastric cancer, the second most common cause of cancer death world- wide. In the long term a vaccine will be the best and most cost effective way to control this ....Helicobacter pylori (H. pylori) is the most common gastro-intestinal pathogen worldwide and infects up to 20 % of the Australian population. Infection is thought to be acquired in childhood, and may cause acute or chronic gastritis, and gastric ulcer later in life. H. pylori infection is also strongly associated with the development of gastric cancer, the second most common cause of cancer death world- wide. In the long term a vaccine will be the best and most cost effective way to control this disease. Vaccination against H. pylori is effective in laboratory animal models. A few vaccines have entered the early phases of clinical trials in human volunteers, however the results have been disappointing. We still do not understand how vaccination leads to killing of bacteria in the stomach, although it is known that antibodies are not responsible. A better understanding of how vaccination works in mice will help the design of vaccines for humans. In a novel approach to study vaccination, the gene expression pattern in the stomachs of immunized mice was analyzed using DNA micro-array technology. In this way we identified several novel genes, and as a result we have developed a new theory for how vaccination might lead to killing H. pylori. We propose that a combination of factors, act together to control H. pylori in the stomach: Leptin, known chiefly as the Obese gene, is a hormone produced by fat cells and controls appetite. Recently leptin has also been shown to influence immune cells (T- cells) in the stomach mucosa. These T-cells in turn send signals to the (epithelial) cells on the surface of the stomach which induces them to produce other proteins; some of which we believe may slow the fast-swimming H. pylori bacteria, and some small anti-microbial proteins (defensins), which are able to kill the bacteria directly by making holes in their membranes. The results of this research will be used to help design better H. pylori vaccines for humans.Read moreRead less
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.
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.
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.
Immunomodulatory Molecules Of Parasitic Helminths As Novel Therapeutics For Allergic Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$321,532.00
Summary
Australia has one of the highest rates of asthma in the world with almost 3 million Australians are affected by this disease. Previous research has shown that infection with various types of parasitic worms lessens the severity of asthma. The aim of this research is to find out why this happens and to isolate the ingredients from the parasite that suppress asthma. Once found, these molecules can be used to create new drugs for the prevention of asthma and allergies in children and adults.
Targeting The Human Immune Response To Bacterial Superantigens.
Funder
National Health and Medical Research Council
Funding Amount
$165,424.00
Summary
This research investigates the human immune response to infection with toxin producing bacteria. Toxins activate the human immune system which can lead to serious illness or the development of disease that can progress rapidly and be associated with high rates of morbidity and mortality. Investigating the harmful effects of infection with toxin producing bacteria in humans and the damage caused by their toxins is essential for the development of effective therapeutic strategies.
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.