The Role Of Novel G-Protein Coupled Receptors In Immunity And Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$69,684.00
Summary
Recent advances in molecular biology techniques have resulted in the identification of many novel GPCRs. Novel GPCRs expressed selectively on immune cells display a potential target for novel therapies for inflammatory diseases such as Asthma and Rheumatoid arthritis. This project aims to define the activity and significance of a novel group of GPCRs, the GPR40 family. Outcomes of this project will be further understanding of immune cell development and inflammatory disease development.
Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-tr ....Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-transcriptionally regulate the production and storage of these proteins. The project aims to identify the RNA binding proteins, microRNAs and other novel factors that also regulate them. This is expected to elucidate the post-transcriptional mechanisms of regulation of MC proteases.Read moreRead less
Real-time imaging of the initiation of adaptive immunity in vivo. Understanding the first few hours of an immune response is fundamental to understanding how the human immune system functions. The immune system mounts our responses to infectious diseases, but can also cause autoimmune disease, allergy, and organ graft rejection. We will study how naive antigen-specific T cells first contact antigen in lymph nodes using 2-photon intravital microscopy. The research has the potential to change the ....Real-time imaging of the initiation of adaptive immunity in vivo. Understanding the first few hours of an immune response is fundamental to understanding how the human immune system functions. The immune system mounts our responses to infectious diseases, but can also cause autoimmune disease, allergy, and organ graft rejection. We will study how naive antigen-specific T cells first contact antigen in lymph nodes using 2-photon intravital microscopy. The research has the potential to change the way we think about the clonal selection of lymphocytes, the fundamental theory underlying our understanding of the immune system.Read moreRead less
CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the ....CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the age that an individual first encounters the infection. Our project will identify critical periods in life that direct T cell programming to subsequent protective or destructive responses, providing new insights into the developing immune system that may be exploited to treat disease or develop vaccines.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.
Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic ....Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic substances. Understanding this molecular program of epithelial-immune cell-mediated sensing/repair will be essential to understand how tissue-repair processes can be driven in the lung, an organ critical for respiration and thus life.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 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.
Analysing the protective role of platelets during malaria infection. Platelets protect the host during malarial infection. This project aims to study how platelets kill the malaria parasite by investigating the role of host molecules and their potential as novel antimalarial agents. The role of platelets in the pathogenesis of cerebral malaria syndrome will also be investigated.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100092
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Fluorescence microscopy with optical tweezers: imaging cellular responses. Life relies on the ability of our cells to receive and respond to signals with pinpoint accuracy, involving both chemical and mechanical signals. This equipment will allow scientists to expose cells to both types of signals and measure the response at an unprecedented level of accuracy for the first time.