SiRNA Induced Transcriptional Silencing Of HIV-1: Elucidating The Mechanisms And Exploring Options For Delivery
Funder
National Health and Medical Research Council
Funding Amount
$512,631.00
Summary
Current drug therapy for HIV is for life We have discovered a set of molecules that will turn off the ability of HIV to reproduce itself. These molecules are from a new family of RNA molecules . A single dose of these molecules suppress the ability of the virus to reproduce itself for more than a month. Further we have found ways of extending this supressive ability to greater than one year. These studies will tell us how these molecules work and how they might be effectively administered.
SiRNA Induced TGS Of Retroviruses: Elucidation Of Underlying Mechanisms And Their Application In Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$371,502.00
Summary
AIMS To elucidate changes in DNA that accompany suppression of HIV growth caused by certain unusual RNA molecules that turn off the ability of HIV to reproduce and make the virus dormant within the infected cell. While we have discovered RNA molecules that can do this to HIV in the test tube, we wish to develop similar molecules that can be used in animal models, so that we can decide whether this technology can be developed for use in humans. We also wish to understand more clearlky the mechani ....AIMS To elucidate changes in DNA that accompany suppression of HIV growth caused by certain unusual RNA molecules that turn off the ability of HIV to reproduce and make the virus dormant within the infected cell. While we have discovered RNA molecules that can do this to HIV in the test tube, we wish to develop similar molecules that can be used in animal models, so that we can decide whether this technology can be developed for use in humans. We also wish to understand more clearlky the mechanisms underlying this effect. BACKGROUND These RNA molecules can suppress a range of pathogenic human viruses including HIV-1 in the test tube. Our novel approach appears to induce changes that are long lasting and are less susceptible to mutations by the virus that allow it to become resistant to other therapeutic strategies. RESEARCH PLAN Initially more work will be done in tissue culture to determine the optimal design of these molecules and the best way to administer them. The most promising of these designs will be tested in small groups of infected animals as a preliminary demonstration of efficacy. In parallel experiments will be performed to elucidate the mechanisms undelying the suppressive effects of these molecules. OUTCOMES AND SIGNIFICANCE This work will lead to a significant increase in our understanding of the way replication of HIV is regulated and will develop a promising new therapeutic strategy for this virus that may be applicable to other conditions.Read moreRead less
Processes Underlying Establishment And Maintenance Of The Latent HIV Resevoir And Potential Impact Of Integrase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$318,044.00
Summary
Therapy for HIV-infected individuals is currently able to control the growth of the virus, but cannot eradicate the viral infection. This is due to a pool of CD4+ T lymphocytes which contain HIV DNA in a latent state, ready to reactivate as soon as therapy is interrupted. This project aims to better understand how this pool of latently infected CD4+ T lymphocytes is established and maintained, particularly how it is linked to the essential T cell survival signal from interleukin 7.
Novel Artemisinin-based Combination Therapies For Children Exposed To High Transmission Of Multiple Plasmodium Species
Funder
National Health and Medical Research Council
Funding Amount
$1,378,408.00
Summary
We recently found that the WHO-recommended combination antimalarial therapy artemether-lumefantrine and the candidate regimen dihydroartemisinin-piperaquine were not fully effective for both falciparum and vivax malaria in young PNG children, a group at risk of complications and death. We plan to study two new combinations (artesunate-pyronaridine and artemisinin-naphthoquine) and hypothesise that at least one will prove superior and be used as first-line treatment in PNG and similar countries.
Genetic And Biochemical Analysis Of The PIM/LAM Biosynthetic Pathway In Mycobacteria.
Funder
National Health and Medical Research Council
Funding Amount
$272,250.00
Summary
Tuberculosis (TB) is one of the most devastating diseases in human history. TB kills approximately two millions people each year worldwide, more than any other disease caused by a single infectious agent. The disease has re-emerged in recent years due to the AIDS epidemic and the appearance of TB bacteria that are not killed by currently available antibiotics. New antibiotics must be developed to combat this global health threat. This requires the identification of targets on the bacteria on whi ....Tuberculosis (TB) is one of the most devastating diseases in human history. TB kills approximately two millions people each year worldwide, more than any other disease caused by a single infectious agent. The disease has re-emerged in recent years due to the AIDS epidemic and the appearance of TB bacteria that are not killed by currently available antibiotics. New antibiotics must be developed to combat this global health threat. This requires the identification of targets on the bacteria on which antibiotics can act. One particularly attractive target is the outer coat of the bacterium. Several existing antibiotics target the bacterial coat, yet the ways in which coat is assembled are poorly understood. Two related compounds in the bacterial coat, and unique to TB bacteria, are called PIMs and LAMs. The structures of these compounds are known, and the compounds appear to be essential for the survival of the bacteria in the human host. However, the mechanisms by which PIMs and LAMs are made by the bacteria are very poorly understood. The aim of our research proposal is to better understand the process by which these compounds are made. If this process can be blocked by an antibiotic, then this represents a potential anti-TB therapy which could save millions of lives worldwide.Read moreRead less
Centre Of Research Excellence In Indigenous Children's Healthy EARs (ICHEAR)
Funder
National Health and Medical Research Council
Funding Amount
$2,615,897.00
Summary
The overwhelming burden of otitis media (middle ear inflammation, OM) and the consequences of hearing loss on social and educational outcomes in Indigenous children are indisputable. Our CRE_ICHEAR is a multidisciplinary group of Australia’s experts in OM research, policy and practice guidelines. The CRE will derive better value in terms of discovery, translation and sustainability. Increased Indigenous leadership will raise awareness and advocacy, with greater efficiency of research translation
Enhancing Clinical Management Of Paediatric Malaria In Endemic Areas With Transmission Of Multiple Plasmodium Species
Funder
National Health and Medical Research Council
Funding Amount
$867,511.00
Summary
Malaria remains a major problem for children in developing countries especially where different types of the disease are common. This set of complementary studies, based at an established research site in PNG aims to develop new treatment strategies for childhood malaria. A novel method of giving medicine via a spray under the tongue for sick children before arrival at hospital and modified dosing schedules of an old drug used for treating parasites hidden in the liver will be studied.
Risk Factors, Mechanisms, And Treatment Of Knowlesi Malaria
Funder
National Health and Medical Research Council
Funding Amount
$265,138.00
Summary
The monkey parasite P. knowlesi is an increasing cause of human malaria in SE Asia. My studies on the clinical epidemiology, diagnosis and treatment of non-severe and severe malaria in Malaysia have changed policy. I will further define the clinical epidemiology of malaria patients in this area over time, assess risk factors for knowlesi malaria, and evaluate the role of human and parasite factors in disease severity, and treatment for reducing acute kidney injury in knowlesi malaria.
Intensive Care patients more often than not, develop kidney failure requiring dialysis. Unfortunately there is little information available to inform clinicians of appropriate doses for antibiotics in these patients, putting them at an increased risk of death from ineffective treatment. Our project aims to develop dosing guidelines for the many types of dialysis used globally to achieve concentrations in the blood that optimise antibiotic effects in these most critically ill patients.