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Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test ....Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test the effect of pharmacological inhibition of established molecules such as RIPK2 or IAPs in NOD dependent models for human diseases. Outcomes of this study will be of the utmost interest for the treatment of NOD driven diseases such as Crohn's disease, Blau syndrome or asthma.Read moreRead less
Mechanism of action of an anti-inflammatory compound which targets alternatively activated macrophages. The project will study the mechanism by which a novel anti-inflammatory compound, developed by our commercial partner, suppresses the activity of a population of cells known as alternatively activated macrophages. These cells play a key role in driving allergic inflammation, including the inflammation associated with asthma.
Development of microbial bioproducts for the suppression of inflammation. Asthma and inflammatory diseases are serious health problems that result from excessive inflammation. Exposure to bacteria may reduce inflammation. This project will identify the bacterial components that reduce inflammation and develop them into new anti-inflammatory therapies for asthma.
Impaired innate antiviral immunity predisposes toward virus-associated airway remodelling in childhood asthma. Increased airway smooth muscle (ASM) mass is the major pathological feature of asthma that causes poor lung function. ASM remodelling occurs in early life, is refractory to current treatments and persists into later life. Severe respiratory virus infections in early life are a major risk factor for the development of asthma, yet it remains to be determined whether viruses promote ASM re ....Impaired innate antiviral immunity predisposes toward virus-associated airway remodelling in childhood asthma. Increased airway smooth muscle (ASM) mass is the major pathological feature of asthma that causes poor lung function. ASM remodelling occurs in early life, is refractory to current treatments and persists into later life. Severe respiratory virus infections in early life are a major risk factor for the development of asthma, yet it remains to be determined whether viruses promote ASM remodelling. Previous studies have developed a unique mouse model of childhood asthma and discovered the molecular mechanism by which this tissue tropism develops in response to virus infection. This project will identify new targets for immunomodulation and design new biologics to block ASM remodelling and the deleterious effects of respiratory virus infection in asthmatic subjects. Read moreRead less
The Use Of Inulin-based Adjuvants To Enhance The Effectiveness And Population Coverage Of Influenza Vaccination
Funder
National Health and Medical Research Council
Funding Amount
$250,393.00
Summary
A major obstacle in the development of effective vaccines to protect against bird flu (avian influenza) is the difficulty in producing enough vaccine in a short enough time to be able to protect the population should bird flu become a problem in the human population. Our research is focused on a technique to make vaccines much more effective and thereby reduce the amount of vaccine needed for each person. This would allow many more people to be protected with the same amount of vaccine. This tec ....A major obstacle in the development of effective vaccines to protect against bird flu (avian influenza) is the difficulty in producing enough vaccine in a short enough time to be able to protect the population should bird flu become a problem in the human population. Our research is focused on a technique to make vaccines much more effective and thereby reduce the amount of vaccine needed for each person. This would allow many more people to be protected with the same amount of vaccine. This technology is known as a vaccine adjuvant and we have developed a unique adjuvant based on a natural plant sugar called inulin that has the potential to dramatically enhance existing and new flu vaccines.Read moreRead less
The Early Inflammatory Response To Virulent And Avirulent Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
Innate immune mechanisms are vital components of host defences against pathogens. In this proposal I aim to investigate the particular mechanisms that operate in early defence against influenza virus infection and compare the ability of virulent and avirulent virus strains to (i) be recognized by components of the innate immune system, and (ii) to trigger an early inflammatory response to infection. It is anticipated that virulent virus strains have adapted to avoid recognition by innate cells s ....Innate immune mechanisms are vital components of host defences against pathogens. In this proposal I aim to investigate the particular mechanisms that operate in early defence against influenza virus infection and compare the ability of virulent and avirulent virus strains to (i) be recognized by components of the innate immune system, and (ii) to trigger an early inflammatory response to infection. It is anticipated that virulent virus strains have adapted to avoid recognition by innate cells such as macrophages. By avoiding this route of uptake and destruction, the virus is free to infect and replicate in other cells of the respiratory tract. Furthermore, by evading macrophage entry, the virus avoids triggering the release of early inflammatory mediators from these cells and this may affect both the speed and the magnitude of the subsequent inflammatory response. This study will contribute to a greater understanding of factors involved in initiating and regulating inflammation in the respiratory tract following viral infection. Furthermore, the findings may provide new insights into mechanisms of virulence of influenza and other enveloped viruses.Read moreRead less
Identification of novel markers of inflammation. This project will benefit Australia as it will increase basic understanding of inflammatory processes, result in a new generation of diagnostics for inflammatory diseases that could lead to earlier diagnosis and to monitor treatment, resulting in large economic and health benefit. It may lead to development of novel new therapies using monoclonal antibodies to regulate processes in immune, cardiovascular and infectious diseases. The work will gene ....Identification of novel markers of inflammation. This project will benefit Australia as it will increase basic understanding of inflammatory processes, result in a new generation of diagnostics for inflammatory diseases that could lead to earlier diagnosis and to monitor treatment, resulting in large economic and health benefit. It may lead to development of novel new therapies using monoclonal antibodies to regulate processes in immune, cardiovascular and infectious diseases. The work will generate significant economic spin-offs to the Australian biotechnology industry and will further relationships and training between research and development.Read moreRead less
Development of an effective vaccine for chlamydial infection: optimisation of a non-toxic cholera toxin-based adjuvant to generate a protective mucosal response. Chlamydial genital infections are the most common sexually transmitted infection in Australia and the world and impose a major health burden on the community. Chlamydial infections are also associated with cardiovascular disease, Australia's biggest killer and asthma, another condition that has increased significantly in prevalence in t ....Development of an effective vaccine for chlamydial infection: optimisation of a non-toxic cholera toxin-based adjuvant to generate a protective mucosal response. Chlamydial genital infections are the most common sexually transmitted infection in Australia and the world and impose a major health burden on the community. Chlamydial infections are also associated with cardiovascular disease, Australia's biggest killer and asthma, another condition that has increased significantly in prevalence in the past 10 years. This project will evaluate the effectiveness of a new adjuvant as a first step towards the development of a vaccine to target these important infections.Read moreRead less
Novel lipid-based adjuvants for induction of mucosal immunity. The project will determine if needle-free oral and transcutaneous immunisation using LipoVax, a novel lipid-based antigen delivery system developed by the industry partner, can protect mice against the mucosal pathogens Chlamydia and Helicobacter. We expect to show that this immunisation method can induce protective mucosal immunity against two of the most common infectious organisms affecting mankind. If successful this will allow u ....Novel lipid-based adjuvants for induction of mucosal immunity. The project will determine if needle-free oral and transcutaneous immunisation using LipoVax, a novel lipid-based antigen delivery system developed by the industry partner, can protect mice against the mucosal pathogens Chlamydia and Helicobacter. We expect to show that this immunisation method can induce protective mucosal immunity against two of the most common infectious organisms affecting mankind. If successful this will allow us to develop LipoVax as a new platform technology that can be applied to the development of human vaccines, veterinary vaccines, vaccines for companion animals and vaccines to target infections in feral animals and native wildlife population populations.Read moreRead less
Enhancing immunogenicity of DNA vaccines by targeted delivery to antigen presenting cells. Vaccines have proven to be one of the most effective means of preventing infection and also provide promise as a treatment for cancer. However, the range of effective technologies that make possible the delivery of vaccines that can protect against a broad range of infections is limited. DNA based vaccines are attractive because they are relatively easy to produce against a wide range of infections. Howeve ....Enhancing immunogenicity of DNA vaccines by targeted delivery to antigen presenting cells. Vaccines have proven to be one of the most effective means of preventing infection and also provide promise as a treatment for cancer. However, the range of effective technologies that make possible the delivery of vaccines that can protect against a broad range of infections is limited. DNA based vaccines are attractive because they are relatively easy to produce against a wide range of infections. However, DNA vaccines often provide poor protection against infections. This project will explore a unique technology developed in Australia and that will greatly improve the effectiveness of DNA vaccines against a broad range of diseases. Read moreRead less