Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stick ....Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stickiness of malaria parasites to blood vessels. Our project will tackle the conditions of MP production and define new drugs to prevent it. It also will explain how the brain becomes affected by high numbers of MP. Our results will cast new light on why the brain functions abnormally when its blood vessels become modified.Read moreRead less
Membrane excitability and cellular calcium regulation in the peripheral nervous system under different (patho)-physiological conditions and in inflammatory disease. Studies of cytokine action on neurons and muscle give new insights into functional responses of the nervous system to systemic inflammation and sepsis. In some countries, sepsis is the third most frequent cause of death following heart attack. Elucidating the pathomechanisms allows to develop therapeutic strategies. Electrophysiology ....Membrane excitability and cellular calcium regulation in the peripheral nervous system under different (patho)-physiological conditions and in inflammatory disease. Studies of cytokine action on neurons and muscle give new insights into functional responses of the nervous system to systemic inflammation and sepsis. In some countries, sepsis is the third most frequent cause of death following heart attack. Elucidating the pathomechanisms allows to develop therapeutic strategies. Electrophysiology, Ca2+ regulation and optical membrane potentiometry allow us to monitor early changes in disease on a (sub)cellular level. Experiments on Ca2+ regulation and ion channel function in muscle with different cholesterol membrane contents will help to understand pathomechanisms in high cholesterol diseases, e.g. obesity, on the membrane level long before cardiovascular effects become prominent.Read moreRead less
Central nervous system cytokines and morphine analgesia. Morphine remains the drug of choice for the management of moderate-to-severe pain, however its clinical effectiveness is compromised by the fact that morphine's analgesic (pain reducing) efficacy becomes less effective the more it is administered.. This project will examine how analgesic tolerance develops from a completely new approach: Namely, how stimulation of the immune system within the central nervous system is a crucial factor in t ....Central nervous system cytokines and morphine analgesia. Morphine remains the drug of choice for the management of moderate-to-severe pain, however its clinical effectiveness is compromised by the fact that morphine's analgesic (pain reducing) efficacy becomes less effective the more it is administered.. This project will examine how analgesic tolerance develops from a completely new approach: Namely, how stimulation of the immune system within the central nervous system is a crucial factor in the development of tolerance. Modulation of analgesia by the immune system has not been systematically studied and provides a potentially fertile ground for the development of new techniques in the management of clinical pain.Read moreRead less
Development and Characterization of Chemokine Receptor Mimics. The proposed research will provide important fundamental insights into the molecular events underlying inflammatory diseases and cancer metastasis. The innovative nature of the research and the significance of the results will enhance Australia's international research standing. Moreover, the insights gained from this work will contribute to the development of therapies that will ultimately enhance the quality of life for Australia ....Development and Characterization of Chemokine Receptor Mimics. The proposed research will provide important fundamental insights into the molecular events underlying inflammatory diseases and cancer metastasis. The innovative nature of the research and the significance of the results will enhance Australia's international research standing. Moreover, the insights gained from this work will contribute to the development of therapies that will ultimately enhance the quality of life for Australians.Read moreRead less
Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and r ....Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and research skill base. Young scientists will be trained in state-of-the-art research techniques in a cross-disciplinary environment that is the way of future biological research. The project may identify potential drug targets for malaria or other infectious diseases. The Intellectual Property will be protected and commercialised.Read moreRead less
Molecular response to interferon beta treatment in multiple sclerosis. Inteferon beta (IFNb) is the frontline drug for treatment of multiple sclerosis. However, in many patients this expensive drug provides no benefit, resulting in unnecessary, uncontrolled disease progression, and in a waste of many millions of dollars each year. A common explanation for this treatment failure is the development of neutralising antibodies (NABs). We will establish the prevalence and effects of NABs in Austra ....Molecular response to interferon beta treatment in multiple sclerosis. Inteferon beta (IFNb) is the frontline drug for treatment of multiple sclerosis. However, in many patients this expensive drug provides no benefit, resulting in unnecessary, uncontrolled disease progression, and in a waste of many millions of dollars each year. A common explanation for this treatment failure is the development of neutralising antibodies (NABs). We will establish the prevalence and effects of NABs in Australian patients, use novel techniques to identify biomarkers for IFNb response, evaluate the diagnostic and therapeutic value of the biomarkers, and develop a new test for NABs. Tailored use of this drug, and possible new therapeutic targets, will result, benefiting the patient and community.Read moreRead less
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
Elucidating the regulation of cell death by random mutagenesis of key apoptotic proteins. All organisms need to remove damaged or excessive cells. This cell death process is called apoptosis. Defects in apoptosis result in numerous diseases including cancer, and neurodegenerative and immune disorders. Determining how this process is regulated is of crucial importance for therapeutic intervention. We will utilise a powerful strategy to mutate proteins required for apoptosis so that they no longer ....Elucidating the regulation of cell death by random mutagenesis of key apoptotic proteins. All organisms need to remove damaged or excessive cells. This cell death process is called apoptosis. Defects in apoptosis result in numerous diseases including cancer, and neurodegenerative and immune disorders. Determining how this process is regulated is of crucial importance for therapeutic intervention. We will utilise a powerful strategy to mutate proteins required for apoptosis so that they no longer work, which will allow the identification of protein regions essential for cell death activity . This will lead to identification of potential drug targets to control apoptosis. Elucidating the mechanism of cell death will lead to the development of novel and improved therapies for diseases such as cancer and neurodegenerative disease.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775778
Funder
Australian Research Council
Funding Amount
$196,000.00
Summary
A microarray platform for gene expression analysis and genotyping in biological systems. This technology has substantial benefits for basic science and biotechnology. The ability to rapidly study changes in gene expression in living organisms will benefit agriculture, animal and biomedical science and biotechnology. The Affymetrix platform creates opportunities for new avenues of research, such as studying epigenetic (DNA and protein modifications) mechanisms in development, ageing and disease. ....A microarray platform for gene expression analysis and genotyping in biological systems. This technology has substantial benefits for basic science and biotechnology. The ability to rapidly study changes in gene expression in living organisms will benefit agriculture, animal and biomedical science and biotechnology. The Affymetrix platform creates opportunities for new avenues of research, such as studying epigenetic (DNA and protein modifications) mechanisms in development, ageing and disease. The project falls within the designated national research priority areas of 'promoting and maintaining good health" and the priority goals of "a healthy start to life", "aging well", "aging productively" and "preventative health care."Read moreRead less
Novel human tryptases: their potential role in inflammatory diseases of the young and old. We have discovered a number of novel human tryptases, and while other members of this enzyme family have been implicated in the development of inflammatory diseases (including rheumatoid arthritis), little is known about these new molecules. We aim to characterise these new enzymes by determining what part of the body they are produced in, whether they are associated with specific inflammatory diseases, an ....Novel human tryptases: their potential role in inflammatory diseases of the young and old. We have discovered a number of novel human tryptases, and while other members of this enzyme family have been implicated in the development of inflammatory diseases (including rheumatoid arthritis), little is known about these new molecules. We aim to characterise these new enzymes by determining what part of the body they are produced in, whether they are associated with specific inflammatory diseases, and what target molecules they act on. A better understanding of these factors will increase the chances of finding cures and developing better treatments for important inflammatory diseases of the ageing population.Read moreRead less