The Ontogeny Of TLR Mediated Innate Immune Function In Normal And Atopic Children
Funder
National Health and Medical Research Council
Funding Amount
$463,328.00
Summary
Bacteria are first recognised by the immune system though primitive innate immune pathways which are highly conserved through evolution. The activation of these pathways is critical for the maturation of the immune system. This may explain the rise in immune diseases with cleaner environments (and less innate immune activation). We speculate that functional differences (as a result of environmental or genetic factors) are implicated in the rising rates of allergic disease. This is the first stud ....Bacteria are first recognised by the immune system though primitive innate immune pathways which are highly conserved through evolution. The activation of these pathways is critical for the maturation of the immune system. This may explain the rise in immune diseases with cleaner environments (and less innate immune activation). We speculate that functional differences (as a result of environmental or genetic factors) are implicated in the rising rates of allergic disease. This is the first study to document normal maturation of these innate pathways in early childhood, and to compare this in allergic and nonallergic children. We will do this using existing samples collected as part of previous cohort studies. This study is the logical next step in the quest to define allergy pathogenesis. Whatever the outcome, the findings will be of enormous significance. A better understanding of the development of these pathways is also likely to contribute to more avenues for better-targeted treatment and prevention.Read moreRead less
Development Of A Vaccine For Genital Chlamydia Infections: Protection Against Transmission And Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$322,245.00
Summary
Genital Chlamydia infections are the most common sexually transmitted infection in Australia with annual health costs of 90-160 million dollars. Ifection rates in 15-29 year olds are increasing at 15-20% per year. Antibiotics are currently the treatment of choice, however antibiotic resistance is increasing and most infections are asymptomatic and not treated in the absence of screening programs. The project aims to develop a genital Chlamydia vaccine using a combination of novel antigens.
Antibiotic resistance increases mortality and costs in the Intensive Care Unit (ICU), but the impact of antibiotic therapy has not been adequately studied. We propose to characterise the behaviour of key elements of the bacterial microflora (resistant bacteria and major resistance genes) in response to antibiotics. We have developed new rapid diagnostics to harness these data and this proposal has the potential to greatly improve diagnostic speed and accuracy and thus clinical outcomes.
Regulation Of Pulmonary Immune Responses To Subunit Vaccines Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$509,202.00
Summary
Tuberculosis (TB) remains an enormous health problem world-wide. Improving the effectiveness of anti-TB vaccines is essential for its control. The first approach to improving subunit TB vaccines will be to manipulate the cellular immune response to the vaccine by increasing the positive cytokine signals, or reducing inhibitory effects on the immune response. The second approach is to develop new subunit vaccines to deliver to the lung in order to increase the potency of the protective response.
Immunomodulatory Effects Of Omega-3 Polyunsaturated Fatty Acids : Role In Allergy Prevention In Infancy
Funder
National Health and Medical Research Council
Funding Amount
$537,600.00
Summary
The dramatic increase in asthma and allergic disease over the last 20-30 years has highlighted the urgent need to identify associated environmental changes that may also be logical targets for disease prevention. Although this is likely to be multifactorial, one significant change during this period has been a progressive decline in the intake of dietary anti-inflammatory n-3 polyunsaturated fats (PUFA) in Western diets, with a corresponding increase in n-6 PUFA fatty acids. We recently showed f ....The dramatic increase in asthma and allergic disease over the last 20-30 years has highlighted the urgent need to identify associated environmental changes that may also be logical targets for disease prevention. Although this is likely to be multifactorial, one significant change during this period has been a progressive decline in the intake of dietary anti-inflammatory n-3 polyunsaturated fats (PUFA) in Western diets, with a corresponding increase in n-6 PUFA fatty acids. We recently showed for the first time that n-3 PUFA may have more significant effects in very early life before immune responses are fully established. We confirmed that maternal fish oil supplementation (n-40) resulted in significantly higher n-3 PUFA levels in newborns (compared to those with no supplements, n-43), and this was related to reduced immune responses to allergens (such as house dust mite, cat and egg). These observations suggest that n-3 PUFA can modify early immune development. Although this previous study was designed to assess immune outcomes (rather than clinical outcomes) we collected preliminary clinical data for the purposes of this application. We observed a consistent trend for less allergic symptoms and sensitisation in the supplementation group. These observations clearly warrant this proposed study to confirm these clinical effects, and to assess the mechanisms of action in considerably more detail. In this proposed study we will compare the effects of fish oil (n-165) or placebo (n-165) in early infancy (from 0-6 months of age). This much larger population will allow us to determine if increasing dietary n-3 PUFA is a way of reducing the chance of allergy in families where there is a high genetic risk. Approximately 40% of infants in Australia will go on to develop asthma or allergies. Strategies such as this that reduce the risk (even slightly) or the severity of disease expression could have enormous impact in this global context at relatively little cost.Read moreRead less
Chronic Bacterial Infection And The Generation Of T Cell Memory: Implication For Vaccination Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Two million people die from tuberculosis (TB) each year. The immune system is unable to eradicate the TB bacterium, and the type of immune response needed to protect against the disease is poorly understood. We will use animal models of TB infection and sophisticated immunological techniques to decipher how the TB bacterium interacts with the immune sytem and causes disease. We will also develop new TB vaccines that aim to boost the immune response in the lung, the main site of TB infection.
The rapid emergence and spread of antibiotic resistance in bacteria that cause infectious diseases is of major concern to public health authorities throughout the world. Many of the genes that are responsible for this resistance are carried on mobile genetic elements, which are discrete segments of genetic material that can move from one bacterium to another. These genetic elements are important vehicles for the transmission of virulence and antibiotic resistance genes in most bacteria. This pro ....The rapid emergence and spread of antibiotic resistance in bacteria that cause infectious diseases is of major concern to public health authorities throughout the world. Many of the genes that are responsible for this resistance are carried on mobile genetic elements, which are discrete segments of genetic material that can move from one bacterium to another. These genetic elements are important vehicles for the transmission of virulence and antibiotic resistance genes in most bacteria. This project is centred on bacteria that cause intestinal diseases and have the potential to transfer genetic information to other bacteria that are present in the intestine. The focus will be on elucidating the mechanism of action of an enzyme encoded by two of these genetic elements. This enzyme is responsible for the movement of these elements from one site in the bacterial genome to another, by a process that is being increasingly recognised as important in antibiotic-resistant disease-causing bacteria. The project will employ the latest tools of molecular biology to determine the function of this enzyme, and its associated genetic elements, at the detailed molecular level. These studies will contribute to our understanding of how these antibiotic resistance elements are transferred within and between different bacterial cells. In the longer term the project will contribute towards the development of improved methods for the control and treatment of infectious diseases.Read moreRead less
Attenuated And Recombinant Mycobacterial Strains As Novel Vaccines To Control Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$370,500.00
Summary
Tuberculosis is a major worldwide health problem. Around one third of the world s population is infected with the bacterium that causes tuberculosis, which results in 2 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. This proj ....Tuberculosis is a major worldwide health problem. Around one third of the world s population is infected with the bacterium that causes tuberculosis, which results in 2 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. This project aims to develop and test novel vaccines to prevent tuberculosis. We will produce forms of the existing BCG vaccine that have been altered to boost the components of the immune system needed to provide optimal protection against tuberculosis. Other potential vaccines that we will test are very similar to the bacterium that causes tuberculosis but have been altered such that they do not cause disease. Using animal models of tuberculosis and sophisticated immunological techniques we wish to determine if these live vaccines can stimulate the right type of immune response needed to fight tuberculosis and prevent infection. This is an internationally competitive project and our team is at the forefront of this research effort. A new, effective tuberculosis vaccine would be a major medical breakthrough and a represent a significant achievement for Australian health and medical research.Read moreRead less
Coordinate Expression Of Virulence Factors In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Escherichia coli is a versatile pathogen capable of causing a range of disease types including diarrhoea, dysentery, haemolytic uremic syndrome, bladder and kidney infections, septicaemia, pneumoniae and meningitis. Infections due to pathogenic E. coli may be limited to mucosal surfaces or can disseminate throughout the body. Amongst the different classes of pathogenic E. coli, diarrheagenic strains (namely enterotoxigenic and enteroinvasive E. coli) are responsible for the death of an estimated ....Escherichia coli is a versatile pathogen capable of causing a range of disease types including diarrhoea, dysentery, haemolytic uremic syndrome, bladder and kidney infections, septicaemia, pneumoniae and meningitis. Infections due to pathogenic E. coli may be limited to mucosal surfaces or can disseminate throughout the body. Amongst the different classes of pathogenic E. coli, diarrheagenic strains (namely enterotoxigenic and enteroinvasive E. coli) are responsible for the death of an estimated one million humans per year, mainly in third world countries. The majority (80%) of urinary tract infections (UTIs) in humans are caused by E. coli and in Australia alone there are about 250,000 cases per year. It is estimated that one in four women and one in twenty men will develop a urinary tract infection in their lifetime. Pathogenic E. coli strains are normally equipped with multiple virulence factors and there is mounting evidence that the expression of such factors is finely orchestrated by mutual regulatory cross-talk. For example, expression of flagella (which provide motility) and adhesins (which provide attachment) are fundamentally counteracting phenotypes, yet the molecular and genetic mechanisms that coordinate their expression are unknown. I plan to examine inter-system cross-regulation of bacterial surface structures (namely adhesins, autoaggregaters, capsules and flagella). The aim is to understand on the molecular level how microorganisms orchestrate expression of virulence factors and will have consequences for our understanding of microbial pathogenicity. The strategy outlined may lead to new routes for strain attenuation and perhaps a method for vaccine strain construction. The research will be performed in collaboration with international high profile partners.Read moreRead less
Molecular Approaches To Developing Subunit Vaccines With Improved Efficacy Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
Tuberculosis remains a major worldwide health problem, resulting in approximately 3 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. The bacterium that causes tuberculosis is made up of may proteins, some of which are known to ....Tuberculosis remains a major worldwide health problem, resulting in approximately 3 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. The bacterium that causes tuberculosis is made up of may proteins, some of which are known to induce immune responses in animals and humans. We will produce vaccines that are made from 13 of these important proteins. Using a laboratory animal model that closely mimics human tuberculosis infection, together with sophisticated immunological techniques, we will determine if these vaccines stimulate the right immune response to fight tuberculosis and prevent infection. In addition, we will exploit molecules known to boost immune responses to optimise these vaccines. Further we will study the recently sequenced genome of the tuberculosis bacterium to identify new proteins that may be included in these novel anti-tuberculosis vaccines. This is an internationally competitive project and our team is at the forefront of this research effort. A new, effective tuberculosis vaccine would be a major medical breakthrough and a represent a significant achievement for Australian health and medical research.Read moreRead less