Discovery Early Career Researcher Award - Grant ID: DE130100537
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Neural regulation of immunity following brain injury. Following a brain injury, the brain tries to protect itself by blocking all inflammation. However, this renders the host with impaired immunity and increased risks to infections. The project aims to delineate the mechanisms behind this response, with the expected outcome of highlighting the important interplay between the nervous and immune system.
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.
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
Toll-like receptors in infectious and inflammatory diseases: the double-edged sword of innate immunity. The innate immune system is the first line of defence against invading microorganisms. This project will explore the role of specific innate immune genes in the control of infections and the development of inflammatory diseases.
Designing new generation adjuvants for allergy and parasite vaccines. Allergy vaccines have the potential to provide a permanent cure against many allergic diseases, currently affecting 20-30 per cent of people in developed countries. This project will study how allergy vaccines work and how we can improve their effectiveness and safety.
Understanding and regulating autoimmune disease through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) family transcription factor, v-rel reticuloendotheliosis viral oncogene homolog B (RelB). This program is well-aligned with the national research priority: Promoting and Maintaining Good Health. The disabling conditions rheumatoid arthritis and type 1 diabetes affect over 1% of Australia's population. They are incurable, so disability and the need for treatment p ....Understanding and regulating autoimmune disease through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) family transcription factor, v-rel reticuloendotheliosis viral oncogene homolog B (RelB). This program is well-aligned with the national research priority: Promoting and Maintaining Good Health. The disabling conditions rheumatoid arthritis and type 1 diabetes affect over 1% of Australia's population. They are incurable, so disability and the need for treatment persist into old age and life expectancy is reduced. The program focuses on more effective and safer treatment, and future disease prevention, with immune therapy. This will have social and economic benefits to Australia. The research will advance Australia's intellectual leadership in Immunology, providing research training and career opportunities, and will lead to strong collaborations between basic scientists, clinicians and industry.Read moreRead less
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
Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight i ....Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight into CTL generation by providing greater understanding of how multicellular systems function both at the cellular and molecular level.Read moreRead less
Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur betwee ....Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur between cells of the immune system during infectious diseases. The insight provided by this project will facilitate the design of better vaccines for protection against diseases, including influenza.Read moreRead less