Cells of the macrophage lineage, the immune system's scavenger cells which attack invading organisms and other infected cells, are important targets of HIV infection, are among the first cells to become infected when the virus is transmitted from person to person and serve as reservoirs of the virus throughout disease progression. Monocytes in the blood, the precursers to macrophages in the tissues, are not very susceptible to infection with HIV but we and others have shown that small numbers ar ....Cells of the macrophage lineage, the immune system's scavenger cells which attack invading organisms and other infected cells, are important targets of HIV infection, are among the first cells to become infected when the virus is transmitted from person to person and serve as reservoirs of the virus throughout disease progression. Monocytes in the blood, the precursers to macrophages in the tissues, are not very susceptible to infection with HIV but we and others have shown that small numbers are infected throughout an infected person's life and that they remain infected despite years of treatment with potent combination drug therapies which reduce the amount of virus in the blood to undetectable levels. We have evidence that suggests that a certain subset of monocytes may be preferentially infected with HIV and may contribute significantly to its persistence in the body. This subset is known to be expanded in response to certain infections, probably including HIV, and during inflammation. We have shown that these cells accumulate in the brains of HIV-infected people especially those with AIDS related dementia. In this project we will characterise these cells in the blood and test our hypothesis that ongoing infection in this subset of monocytes plays an important role in the course of HIV disease and contributes to the persistence of HIV infection and the failure of currently available therapies to eradicate it.Read moreRead less
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.
Determination Of Disease Specific Epitopes In Rheumatic Heart Disease In Australia
Funder
National Health and Medical Research Council
Funding Amount
$374,817.00
Summary
Rheumatic Fever and Rheumatic Heart Disease (RF-RHD) remain a significant cause of illness in Aboriginal communities in Australia. RF-RHD is a complication which follows infection with a specific bacterium. The purpose of this study is to compare the body's response and find out the patterns of antibody and immune cell reactivity to the bacterium and body proteins in RF-RHD patients and controls. It will also enable us to study the mechanisms that initiate the disease process.
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.
Comparative Pathophysiology And Clinical Epidemiology Of Knowlesi Malaria
Funder
National Health and Medical Research Council
Funding Amount
$267,172.00
Summary
The simian parasite P. knowlesi is the most common cause of malaria in Malaysia and can cause severe and fatal disease. We are currently conducting a study of all malaria patients admitted to a tertiary referral hospital in Sabah, Malaysia. This will allow us to describe the epidemiological and clinical features of the hospitalised patients, including changes over time. We are also conducting novel pathophysiological studies which will allow us to understand how P. knowlesi causes sever disease.
A Comparative Study Of The Pathophysiology Of Severe Knowlesi And Falciparum Malaria
Funder
National Health and Medical Research Council
Funding Amount
$660,293.00
Summary
Plasmodium knowlesi causes monkey malaria, but has recently been found to infect humans resulting in severe disease and death similar to Plasmodium falciparum. Clinical features of severe P. knowlesi and how it causes complications are poorly described and understanding this could improve treatment and outcomes. In patients with P. knowlesi, we want to describe the clinical features, the ability to cause severe disease, and measure 1) markers of platelet activation and 2) capillary obstruction a ....Plasmodium knowlesi causes monkey malaria, but has recently been found to infect humans resulting in severe disease and death similar to Plasmodium falciparum. Clinical features of severe P. knowlesi and how it causes complications are poorly described and understanding this could improve treatment and outcomes. In patients with P. knowlesi, we want to describe the clinical features, the ability to cause severe disease, and measure 1) markers of platelet activation and 2) capillary obstruction and red cell deformability,Read moreRead less
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
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.
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.
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.