Determining The Synergistic Effects Of Complementary Medicines On Pro-inflammatory Cytokines,
Funder
National Health and Medical Research Council
Funding Amount
$290,412.00
Summary
Diseases like influenza, commonly called ‘the flu’, produce symptoms such as fever, headaches, lethargy and lack of appetite. What most people don’t realise is that it is not the influenza virus that produces these symptoms, but the body’s immune response to the influenza virus. This immune response comes about because the influenza virus stimulates cells to produce molecules called cytokines, and cytokines have many effects in the body, including causing fever and a lack of appetite. In severe ....Diseases like influenza, commonly called ‘the flu’, produce symptoms such as fever, headaches, lethargy and lack of appetite. What most people don’t realise is that it is not the influenza virus that produces these symptoms, but the body’s immune response to the influenza virus. This immune response comes about because the influenza virus stimulates cells to produce molecules called cytokines, and cytokines have many effects in the body, including causing fever and a lack of appetite. In severe infections like those caused by the influenza virus responsible for the pandemic of 1918, and during “bird ‘flu” (H5N1) infections, people die because the immune response becomes overwhelming. Cytokines produced during these sorts of responses are actually very harmful, even though in small amounts they help to kill the virus and cure the infection. Researchers working in this field have likened these severe responses to a “cytokine storm”. This project focusses on finding alternative therapies such as those used in Chinese medicine to prevent a cytokine storm happening, so that if an influenza pandemic occurs these treatments could be quickly made available to everyone. Examples are the Chinese herbs Angelica sinensis and Salvia miltiorrhiza. Recent laboratory studies in New York have shown that both of these herbs have potent cytokine effects, decreasing levels of an inflammatory cytokine known to be associated with death in both malaria and sepsis. Our study aims to closely examine the effects of these Chinese herbs, as well as other commercially available herbal extracts, and traditional combinations of herbs, to find synergies between them that could be used to treat severe influenza infections.Read moreRead less
Screening Agents Active Against The Late-stage Inflammatory Cytokines For Activity Against Influenza Disease
Funder
National Health and Medical Research Council
Funding Amount
$241,409.00
Summary
Infection with a virulent influenza virus that the body has never encountered before, particularly H5N1, sends the immune system into overdrive, and causes a massive release of proteins (inflammatory cytokines), known as a cytokine storm, that in and of itself leads to death. The object of this research is to screen, in a mouse influenza model, agents known to prevent this occurring and antagonise it once it has occurred. This will be done with and without Tamiflu, a standard anti-influenza drug ....Infection with a virulent influenza virus that the body has never encountered before, particularly H5N1, sends the immune system into overdrive, and causes a massive release of proteins (inflammatory cytokines), known as a cytokine storm, that in and of itself leads to death. The object of this research is to screen, in a mouse influenza model, agents known to prevent this occurring and antagonise it once it has occurred. This will be done with and without Tamiflu, a standard anti-influenza drug.Read moreRead less
Roles Of Enzymes Of The Dipeptidyl Peptidase Gene Family In Human Liver
Funder
National Health and Medical Research Council
Funding Amount
$79,750.00
Summary
Chronic liver diseases, particularly those caused by autoimmune disease, alcohol and Hepatitis B and C virus infection, are major causes of morbidity and mortality in our community. They are characterised by progressive scarring of the liver which finally leads to liver failure and the need in many cases for organ transplantation. Each year 15,000 Australians become infected, probably for life, with hepatitis C virus. Unless more effective treatments are developed approximately 20% of these infe ....Chronic liver diseases, particularly those caused by autoimmune disease, alcohol and Hepatitis B and C virus infection, are major causes of morbidity and mortality in our community. They are characterised by progressive scarring of the liver which finally leads to liver failure and the need in many cases for organ transplantation. Each year 15,000 Australians become infected, probably for life, with hepatitis C virus. Unless more effective treatments are developed approximately 20% of these infections will progress to liver failure or liver cancer within 30 years. Diabetes afflicts 150 million people, and 90% have Type 2 diabetes. We request funding of our research on a family of enzymes highly prospective as targets for novel therapies for these diseases. We are internationally recognised experts on this enzyme family and on liver disease. The prototype member of this enzyme family, dipeptidyl peptidase (DP) IV, is being targeted by novel drugs that are in phase III clinical trials for Type 2 diabetes. Family member fibroblast activation protein (FAP) is targeted by novel anti-cancer drugs We were first to clone and lodge patent applications for two new enzymes of this family, DP8 and DP9. Our research proposal would lead to determination of whether FAP, DP8 and-or DP9 are valuable targets for novel liver disease therapeutics and facilitate generating the development of such therapeutics by a more thorough understanding of the activities and roles of these enzymes Completion of this project will greatly increase our understanding of these enzymes and their roles in chronic liver injury. This work can potentially lead to the development of specific inhibitors of enzyme function designed to relieve liver damage.Read moreRead less
A link between periodontal disease, inflammation of the gums, and cardiovascular disease has been suggested in recent studies, however the evidence remains uncertain. Supporting the link are data that inflammation predisposes to atherosclerosis and heart attacks. Patients in the PERICAR study will have blood tests before and after periodontal treatment so that researchers can study whether treatment reduces factors in the blood that have previously been shown to indicate the risk of cardiovascul ....A link between periodontal disease, inflammation of the gums, and cardiovascular disease has been suggested in recent studies, however the evidence remains uncertain. Supporting the link are data that inflammation predisposes to atherosclerosis and heart attacks. Patients in the PERICAR study will have blood tests before and after periodontal treatment so that researchers can study whether treatment reduces factors in the blood that have previously been shown to indicate the risk of cardiovascular disease. This study will provide further clues to this potentially very important and treatable relationship.Read moreRead less
Novel Probiotics And Naturally-sourced Extracts As Treatment Strategies For Chemotherapy-induced
Funder
National Health and Medical Research Council
Funding Amount
$322,183.00
Summary
Intestinal mucositis is a serious disorder associated with chemotherapy treatment in cancer patients. Recently, a new strain of probiotic bacteria has been described with the potential to decrease the severity of intestinal mucositis. However, it is not known whether the live probiotic is necessary for this effect. We will compare the live probiotic, dead probiotic and factors sourced from this probiotic for the potential to decrease the severity of intestinal mucositis. Similarly, there have be ....Intestinal mucositis is a serious disorder associated with chemotherapy treatment in cancer patients. Recently, a new strain of probiotic bacteria has been described with the potential to decrease the severity of intestinal mucositis. However, it is not known whether the live probiotic is necessary for this effect. We will compare the live probiotic, dead probiotic and factors sourced from this probiotic for the potential to decrease the severity of intestinal mucositis. Similarly, there have been anecdotal claims of medicinal application for so-called ‘bioactive’ extracts and formulations derived from a range of mammalian, marine and plant sources. Specifically, Lyprinol (an extract derived from the New Zealand Green-Lipped Mussel), Emu Oil (derived from Emu meat) and the herbal extract Iberogast, have been reported to possess antiinflammatory properties. Indeed, these agents are used widely for the adjunctive relief of symptoms associated with arthritis and joint pain. However, these agents have yet to be tested for their potential to treat or prevent intestinal mucositis. For the first time, utilizing proven, controlled animal model systems, the current submission will explore the therapeutic potential of these agents, alone and in combination with indicated probiotics, for their capacity to treat or prevent mucositis. Should efficacy be demonstrated, a potential mechanism of action will be sought by investigating effects on intestinal stem cells.Read moreRead less
Validation And Replication Of Genes Associated With Common Human Disease Using Australian Twin Families
Funder
National Health and Medical Research Council
Funding Amount
$921,224.00
Summary
The European Network for Genetic and Genomic Epidemiology (ENGAGE) aims to translate the wealth of data emerging from large-scale research efforts in molecular epidemiology into information of direct relevance to future advances in clinical medicine. ENGAGE will do this through the integration of very large datasets already available from a substantial number of large and well-characterised samples. The resulting ENGAGE resource will represent a research investment >€100M (>AU$160M) and pr ....The European Network for Genetic and Genomic Epidemiology (ENGAGE) aims to translate the wealth of data emerging from large-scale research efforts in molecular epidemiology into information of direct relevance to future advances in clinical medicine. ENGAGE will do this through the integration of very large datasets already available from a substantial number of large and well-characterised samples. The resulting ENGAGE resource will represent a research investment >€100M (>AU$160M) and provide unprecedented power to discover disease and trait susceptibility genes. QIMR will contribute 12,000 twins for ENGAGE joint analyses and provide analytical expertise in the analysis of disease and genetic data related to lifestyle and metabolic traits, with particular emphasis on cardiovascular disease, type 2 diabetes and migraine risk factors. Our laboratory will also perform vital further genetic studies to establish the causal relationship between the genetic variants concerned and the traits of interest. Most importantly, our direct participation will allow the translation of these findings into the Australian population and clinical arena.Read moreRead less
Provision Of Secondary Cardiac Preventive Australian General Practice
Funder
National Health and Medical Research Council
Funding Amount
$499,513.00
Summary
This study will provide a comprehensive description of secondary preventative activities for patients with ischaemic heart disease, with the aim of determining those factors that can most contribute to reducing the increased risk of further events which they experience, and thereby reducing the burden of this disease.
Gene-environment Interaction In Healthy Brain Ageing And Age Related Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$2,162,805.00
Summary
Healthy ageing is characterised by low level of disability, high cognitive and functional capacity, and an active engagement in life. The most important ingredient of healthy ageing is a healthy brain, bereft of age-related diseases and dysfunction. Brain ageing and brain diseases are determined by multiple genetic factors that interact with environmental influences. The genes are multiple, the majority of which have a small influence. This study is an attempt to identify some of these genes and ....Healthy ageing is characterised by low level of disability, high cognitive and functional capacity, and an active engagement in life. The most important ingredient of healthy ageing is a healthy brain, bereft of age-related diseases and dysfunction. Brain ageing and brain diseases are determined by multiple genetic factors that interact with environmental influences. The genes are multiple, the majority of which have a small influence. This study is an attempt to identify some of these genes and investigate their interactions with environmental factors. It will use a unique resource, the NHMRC Australian Twin Registry (ATR) to identify elderly twins, and will also include the siblings of these twins so as to increase the ability to identify the important factors. The participants, who are listed on the ATR and recruited from NSW, Queensland and Victoria, will receive detailed neurological, psychiatric and cognitive assessments, and will undergo brain MRI scans. Their blood samples will be used to measure key chemicals that may affect brain ageing and to extract DNA for genetic tests. They will be followed-up every two years thereafter, and changes in their brain structure and cognitive functioning will be examined. Available statistical models will be used to examine gene-environment interactions and specific genes will be explored for their contribution to the additive genetic effects. This study will yield an important resource for national and international collaborations and has the potential to discover new genes.Read moreRead less
Predictors And Consequences Of Allergies That Impact On Children Getting A Healthy Start To Life:a Prospective Study
Funder
National Health and Medical Research Council
Funding Amount
$893,559.00
Summary
Allergic diseases prevent Australian children getting a healthy start to life by causing long term illnesses. This group of diseases includes asthma, hay fever, eczema and food allergies. Half of all Australian children are born into families with a history of these conditions and these children are at increased risk. Some of these children develop allergies while the others do not. It is also known that allergic conditions change over time, but we have no information on causes of these changes. ....Allergic diseases prevent Australian children getting a healthy start to life by causing long term illnesses. This group of diseases includes asthma, hay fever, eczema and food allergies. Half of all Australian children are born into families with a history of these conditions and these children are at increased risk. Some of these children develop allergies while the others do not. It is also known that allergic conditions change over time, but we have no information on causes of these changes. For example some infants with eczema continue to have eczema or develop hay fever and asthma, while others do not. The aim of this study is to determine what factors cause allergies and what factors influence these changes. This will provide evidence to guide health policy and clinical practice. Looking at the different conditions in family members over time is a good way to answer these types of questions, because parents and siblings share similar exposures, but not all the same genes. This helps to disentangle the effects of the environment and genes. The Melbourne Atopic Cohort Study (MACS) is amongst the world�s major studies on the development of allergies. MACS commenced in 1991-94 by recruiting 620 babies prior to birth. Only infants born into families with a history of allergic disease were included. MACS is unique because all family members and the home environment were assessed at the time of birth of the child. These children have been followed regularly over the first ten years of their life. The MACS now provides a unique opportunity to conduct a family study that can examine genes, childhood environment and individual risk factors for allergies. This will also allow exploration of the impact of allergies on families and the health care system, and how we can reduce that impact. Such information will provide evidence to guide health care policy and clinical practice. Also, the current study will provide a platform for future studies to investigate the progression of allergies in this family cohort. This will be the world's only longitudinal family follow-up of allergies that spans all of childhood. It will assist in reducing the impact of these common conditions, and the findings will be original and significant not only in Australia but also internationally.Read moreRead less