RNAi Therapeutic Intervention Of Human Viral Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$584,117.00
Summary
Human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. HMPV is emerging as a major cause of morbidity and life-threatening respiratory tract disease in infants, young children and the elderly worldwide. No treatment is currently available. The objectives of this proposal are to develop novel antiviral drugs that silence the expression of viral genes and to examine protection against the disease.
Mechanism/s Of Disease Caused By Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$479,517.00
Summary
A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract ill ....A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract illness similar to RSV, but with an unknown etiology, suggests that HMPV may mediate similar clinical pathology. Nothing is currently known about the immune response to HMPV, or the association of these responses with lung disease. The objectives of this proposal are to elucidate the mechanisms of immunity and disease pathogenesis associated with human metapneumovirus (HMPV) and to investigate the use of a novel vaccine to protect against HMPV infection. Once this data is obtained, the study will provide the foundation for further research in the development of vaccines or therapeutic protocols to treat HMPV. It will also provide valuable information for understanding the disease in humans. Also,it is likely that HMPV, like hRSV, may prove to be an agent associated with long-term decreased pulmonary function and airflow limitation perhaps developing to asthma.Read moreRead less
Quit In General Practice: A Cluster Randomised Trial Of Enhanced In-practice Support For Smoking Cessation
Funder
National Health and Medical Research Council
Funding Amount
$1,117,241.00
Summary
Tobacco smoking remains the most common preventable cause of death and illness in Australia today. Smoking cessation programs are some of the most effective and cost effective strategies that can be undertaken in health care settings, including general practice. This project will test a new approach to supporting smoking cessation in general practice. This involves the practice nurse, GP and Quitline working in partnership to provide a flexible program of suport to meet the needs of smokers.
Chronic Disease Outcomes And Enhanced Primary Care In Seniors: A Cross-Jurisdictional Linkage Project
Funder
National Health and Medical Research Council
Funding Amount
$1,077,766.00
Summary
This project will provide evidence on how best to use the efforts of Australian GPs to obtain better outcomes in patients aged 65+ years who suffer from chronic diseases such as diabetes, heart disease and high blood pressure, asthma and emphysema, seizures and stomach disorders. It will also examine the best way that GP visits can promote healthier ageing in all older seniors, aged 75+ years. For each disease and in older seniors, the study will be able to detect which of the following factors ....This project will provide evidence on how best to use the efforts of Australian GPs to obtain better outcomes in patients aged 65+ years who suffer from chronic diseases such as diabetes, heart disease and high blood pressure, asthma and emphysema, seizures and stomach disorders. It will also examine the best way that GP visits can promote healthier ageing in all older seniors, aged 75+ years. For each disease and in older seniors, the study will be able to detect which of the following factors are the most important for better patient health: (i) seeing a GP more times, (ii) seeing a GP at more even intervals, (iii) seeing the same GP, or (iv) seeing a GP with a lot of experience in chronic diseases. Separate investigations will be made in older people living in hostels and nursing homes, because their needs may be different. The study will also evaluate the benefits of a major change that occurred to Medicare in 1999, when GPs were paid to perform health assessments and to prepare health plans (with other health workers) for patients with chronic health problems. The results will enable this important initiative to be further improved. The study will use a unique and new Australian research facility, which has brought together health data on the entire population of WA from both the State and Commonwealth levels, including information on Medicare use, pharmaceuticals, hospital stays and deaths. The facility works in such a way as to preserve patient and GP privacy. A strong feature of this research will be the degree of involvement of a representative and voluntary group of older Australian patients who attend GP clinics, and the GPs themselves, in advising the researchers on what's important to consumers and GPs.Read moreRead less
Mechanisms Of Induction And Progression Of Childhood Asthma: Investigations In A Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$517,586.00
Summary
This project investigates how certain respiratory viral infections in very young children might predispose to developing asthma, and how inflammation in the airways in asthma might then worsen. The experimental work, which will use unique mouse models developed in the laboratories of the chief investigators, will focus on changes in genes that control the pattern of immune response to allergens and that regulate the progression of inflammation.
Improving Medication Safety In Seniors: A Cross-Jurisdictional Linkage Project
Funder
National Health and Medical Research Council
Funding Amount
$636,717.00
Summary
The project will identify priorities for tackling the current epidemic of hospitalisation of Australians aged 65+ years due to side effects of their medications. Two different groups of medications will be investigated. The first will be the prescribed drugs most often recorded as causes of hospital stay, including those taken to stop blood clotting, for high blood pressure and other cardiovascular problems, for rheumatism or strong pain relief, anti-cancer drugs and steroids. The study will exa ....The project will identify priorities for tackling the current epidemic of hospitalisation of Australians aged 65+ years due to side effects of their medications. Two different groups of medications will be investigated. The first will be the prescribed drugs most often recorded as causes of hospital stay, including those taken to stop blood clotting, for high blood pressure and other cardiovascular problems, for rheumatism or strong pain relief, anti-cancer drugs and steroids. The study will examine which of these drugs taken under what circumstances has the highest risk, so prevention can be better targeted. The study will investigate if adequate laboratory monitoring of the anti- clotting drugs is taking place and whether the guidelines should be updated. The second group will be 68 medications that should be avoided in seniors according to an international expert panel. The research will see how often these 'inappropriate medications' are still prescribed in the Australian setting, and the size of their contributions to unplanned hospital stays. The researchers suspect that this problem is much larger than immediately apparent from routine statistics, because many of the side effects of inappropriate medications are non-specific, such as confusion, drowsiness or difficulty standing up, thus putting seniors at risk of falls and neglect of other aspects of their health. The study will use a unique and new Australian research facility, which has brought together health data on the entire population of WA from both the State and Commonwealth levels, including information on pharmaceuticals, Medicare use, hospital stays and deaths. The facility works in such a way as to preserve patient and GP privacy. A strong feature of this research will be the degree of involvement of a representative and voluntary group of older Australian patients who attend GP clinics, and the GPs themselves, in advising the researchers on what's important to consumers and GPs.Read moreRead less
A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less
Discovery Of A Novel Immune Evasion Strategy Employed By Mosquito Borne Viruses To Suppress Antiviral Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$418,642.00
Summary
The transition from mosquitoes, ticks, or other invertebrate vectors to the human hosts represents a crucial step in the successful establishment of arthropod borne viruses (arboviruses). The incidence of arbovirus infections such as dengue virus, West Nile virus, Ross River virus is increasing at an alarming rate in various parts of the world. In addition, the emergence of new viruses resulting in significant mortality in the population is of utmost concern. Vaccines for many of these viruses r ....The transition from mosquitoes, ticks, or other invertebrate vectors to the human hosts represents a crucial step in the successful establishment of arthropod borne viruses (arboviruses). The incidence of arbovirus infections such as dengue virus, West Nile virus, Ross River virus is increasing at an alarming rate in various parts of the world. In addition, the emergence of new viruses resulting in significant mortality in the population is of utmost concern. Vaccines for many of these viruses remain elusive. One factor that contributes to this is the ability of viruses to develop ingenious strategies to avoid or suppress the host defence systems, which enable its successful establishment in the host. Understanding how viruses evade-suppress host defence machinery will certainly enhance and improve our approaches to fight them. For the first time internationally we have discovered a new and novel pathway employed by arboviruses to suppress antiviral immune responses in the host. We have discovered that naturally occurring carbohydrates on viruses derived from mosquito cells, would influence these virus s ability to evade-suppress host antiviral proteins such as interferons. This may be a general effect of arboviruses or may even extend to other viruses , which include a number of deadly pathogens (HIV, Influenza). This research has the potential to significantly expand our understanding of how these viruses establish infection and cause disease. Also this discovery has broader implications for understanding inflammatory processes and their regulation.Read moreRead less