The Impact Of Influenza A Virus PB1-F2 Protein On Host Immunity And The Potential For Therapeutic Targeting
Funder
National Health and Medical Research Council
Funding Amount
$317,076.00
Summary
The 1918 influenza virus pandemic resulted in 50 million deaths globally and there is potential for new pandemics, such as the predicted H5N1 Bird Flu . Exact causes of such devastating lethality are not fully identified. Newly discovered influenza A virus (IAV) PB1-F2 protein is present in nearly all highly pathogenic IAVs and promotes virus virulence. This study will further examine the way in which PB1-F2 impacts the host, revealing potential therapeutic targets to lessen disease burden.
Enhancement Of Mucosal Immunity And CTL Avidity Against HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$553,070.00
Summary
Production of strong antiviral immunity at the local mucosa (genito-rectal track) is essential for protection against HIV-AIDS. We believe that expression of small hormone-like molecules known as Th2 cytokines IL-4-IL-13 negatively influence the generation of protective immunity against HIV. Thus we aim to counteract these effects by co-expressing proteins known as chemokines together with vaccine antigens to improve the quality of mucosal vaccine immunity.
Interaction Of Anti-viral IDO And NOS2 In Vivo In A Novel Murine STD Model.
Funder
National Health and Medical Research Council
Funding Amount
$573,629.00
Summary
Sexually transmitted viral diseases (STD) are increasing globally, but we know little of how virus is controlled early in infection. We have shown for the first time in vivo, in our STD model, that during an antiviral immune response, soluble factors turn on an enzyme, indoleamine 2,3-dioxygenase (IDO), to break down and deplete the amino acid, L-tryptophan, starving virus to reduce growth early in STDs. Our project will further define the action and control of IDO in STD.
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.
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
A Detailed Asssessment Of Severe Malaria And Severe Non Malarial Illness In Papua New Guinean Children.
Funder
National Health and Medical Research Council
Funding Amount
$39,171.00
Summary
PNG has the highest infant and childhood mortality in the Pacific with malaria accounting for 15% of infant mortality. Diagnosing and investigating malaria in this setting is hard because the symptoms are similar to other diseases. We aim to accurately describe clinical and laboratory features and risk factors for malaria, severe non malarial disease and mortality. We are investigating an outbreak of unexplained encephalitis as well.
Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for >$1.6 billion in medical expenses each year. It is estimated that 50% of women will develop a UTI in their lifetime. This research aims to understand the processes by which bacteria colonize the human bladder. The work has implications for the development of new approaches to prevent and treat UTI.
Finding Therapeutic Targets For An Opportunistic Human Fungal Pathogen
Funder
National Health and Medical Research Council
Funding Amount
$404,068.00
Summary
Penicillium marneffei is a fungus that causes disease in patients with depressed immunity. This project models this infection in zebrafish, which have advantages for modelling infectious disease. It uses fluorescent fungi and fish with fluorescent immune cells to study the way white blood cells fight this infection, and mutant zebrafish and mutant fungi to find new therapeutic targets in the host-pathogen interaction.
Visualisation Of Gamma-delta T Cell Responses In Cutaneous Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$570,876.00
Summary
Mycobacterial infections remain a major burden of modern society. This proposal aims to define the role of an understudied immune cell subset, gamma-delta T cells, in the response against mycobacteria. We will use cutting-edge multi-photon imaging to track these cells in real-time directly within infected tissues. This will facilitate generating a new vista of anti-mycobacterial immune responses and may aid the development of improved vaccines.