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
The Role Of Capsid Protein Nucleolar Localisation In Chikungunya Virus: Implications For Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Chikungunya virus (CHIKV) is a globally widespread mosquito-borne alphavirus capable of causing considerable human morbidity and mortality. With no CHIKV vaccine or antiviral available this proposal aims to develop a live attenuated CHIKV vaccine, rationally designed by investigating the host cell nucleolar trafficking of CHIKV capsid protein. This vaccine has the potential to provide cross-protection against additional arthritogenic alphaviruses endemic to Australia such as Ross River virus.
Optimising Large-scale Public Health Interventions To Control Neglected Tropical Diseases
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Neglected tropical diseases (NTD) are a group of health conditions that affect the poorest of the poor, particularly in remote and rural areas. They affect the most vulnerable communities and cause substantial, chronic health harms impairing personal and social development. Several debilitating NTD are common in remote indigenous communities and Pacific islands. I propose a series of studies to investigate new strategies to control NTD in large populations where these diseases are endemic.
Arbovirus Activation And Modulation Of NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$779,720.00
Summary
This project aims to establish how mosquito borne viruses such as Ross River and dengue viruses interacts with the human host to cause disease, including how the virus evades the host’s immune response to persist and cause disease for prolonged periods. Knowing how differences in the virus and the host’s immune system interplay to cause asymptomatic to severely disabling disease will assist in devising new treatments and prevention programs to lessen the impact of these diseases in Australia.
Using mathematical modelling to inform HIV/AIDS public health policy. This research will directly inform HIV/AIDS policy officials on the most effective strategies for preventing new cases in HIV in the community. Consequently, there are health benefits for Australia and for the other countries in which the research is being conducted. HIV/AIDS community groups, educators, and other advocacy groups will also be engaged in the research, leading to the development of focussed prevention campaigns ....Using mathematical modelling to inform HIV/AIDS public health policy. This research will directly inform HIV/AIDS policy officials on the most effective strategies for preventing new cases in HIV in the community. Consequently, there are health benefits for Australia and for the other countries in which the research is being conducted. HIV/AIDS community groups, educators, and other advocacy groups will also be engaged in the research, leading to the development of focussed prevention campaigns by these stakeholders to inform the appropriate communities. Reducing the health burdens of HIV/AIDS will also have economic benefits.Read moreRead less
A National Population-based Study Of Rheumatic Heart Disease In Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$877,826.00
Summary
Whilst overall a rare disease, Indigenous peoples have disproportionately high rates of rheumatic heart disease (RHD). This study explores the prevalence and distribution of RHD in pregnancy in Australia and New Zealand. It details current management, diagnostic and referral process and risk factors. Key attributes of culturally safe models of care for RHD in pregnancy are explored, particularly as they relate to Indigenous women. Findings will inform policy, guidelines and education resources.
Prevention Of Beta Cell Destruction In Type 1 Diabetes By Immunotherapy Using Parasite-derived Molecules.
Funder
National Health and Medical Research Council
Funding Amount
$518,443.00
Summary
To prevent type 1 diabetes, compounds that avert the autoimmune destruction of beta cells are needed. We are exploiting the potential of ñworm therapyî by mimicking the beneficial immune effects of parasite worm infection. We have identified the molecules that the parasite uses to influence host immune responses. We have demonstrated that these novel immune-modulatory worm molecules prevent diabetes in a mouse model. This offers great potential for the development of therapeutic interventions.
The Mechanism Of HSV-1 Transport In Sensory Axons And Its Unique Assembly At The Axon Terminus
Funder
National Health and Medical Research Council
Funding Amount
$670,284.00
Summary
Herpes simplex viruses 1 and 2 cause common diseases such as genital herpes and, occasionally, neonatal deaths and encephalitis and predisposes to HIV infection. New antiviral strategies are required for resistant viruses for control. These aims will be facilitated by understanding how HSV is transported down nerves and across into skin. In this study, we will define how a key viral protein plays a major role in assembly of the virus at the tip of the nerve before it enters skin.
Understanding spatial trends in HIV/AIDS infections in South Africa and Australia. This project will develop quantitative methods that will be used to inform public health officials in understanding past and current HIV/AIDS epidemics as well as planning for the future of these epidemics. It will understand not only the behavioural and demographic characteristics of importance as risk factors for HIV infection in South Africa, the epicentre of the global HIV pandemic, but also the geographical s ....Understanding spatial trends in HIV/AIDS infections in South Africa and Australia. This project will develop quantitative methods that will be used to inform public health officials in understanding past and current HIV/AIDS epidemics as well as planning for the future of these epidemics. It will understand not only the behavioural and demographic characteristics of importance as risk factors for HIV infection in South Africa, the epicentre of the global HIV pandemic, but also the geographical spatial locations in which HIV cases are likely to emerge in the future. This project will also forecast the future geographical trends in Australia's changing HIV epidemic in order to plan for intervention strategies and prepare clinical practice appropriately.Read moreRead less