HIV infection of CD4+ lymphocytes leads to a high rate of reproduction of new virus. However, in the brain, HIV infection of the astrocytes does not yield high levels of new virus. HIV is genetically active in these astrocytes, producing high levels of the messenger molecules, the so-called mRNA, that code for the proteins required for a new virus particle. We have determined that these HIV mRNAs are specifically prevented from translating into protein. The mechanisms controlling protein transla ....HIV infection of CD4+ lymphocytes leads to a high rate of reproduction of new virus. However, in the brain, HIV infection of the astrocytes does not yield high levels of new virus. HIV is genetically active in these astrocytes, producing high levels of the messenger molecules, the so-called mRNA, that code for the proteins required for a new virus particle. We have determined that these HIV mRNAs are specifically prevented from translating into protein. The mechanisms controlling protein translation from RNA are relatively poorly understood compared with the other control points of cellular gene expression, such as the synthesis of mRNA. This project examines how astrocytes rapidly detect the presence of HIV mRNA and alter their translation machinery to halt the expression of HIV protein. This host defence mechanism involves two key components; the cellular component that identifies and responds to the viral mRNA, and the structural features of the HIV mRNA that enable the cell to detect its viral origin. We will study how translation of HIV proteins requires both HIV and cellular factors. We will determine the impact of both viral RNA elements and viral RNA binding proteins on the translation of viral and cellular proteins. The contribution of the type-1 interferons that are produced in response to viral infection will be studied for their role in augmenting the inhibition of HIV protein translation. Since HIV infected astrocytes significantly contribute to the onset of AIDS dementia, we will sees a strategy to lock HIV into a dormant state in the brain and thereby prevent the neurodegenerative disease associated with HIV. We will use the anti-viral mechanism blocking HIV protein translation in astrocytes to protect other cell populations, such as the CD4+ lymphocytes, from HIV infection. These studies will also give insights into the general mechanisms for translational control of gene expression in human cells.Read moreRead less
Pathogenic Role Of MicroParticles In Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$250,000.00
Summary
Cerebral malaria (CM) is a life-threatening complication of infection caused by parasites. The mechanisms leading to coma, convulsions and death in CM remain unknown. CM in children is associated with high levels of endothelial microparticles (MP). However, not only the levels but also the phenotypes of MP can be altered in CM as well as their related functional properties. The project aims to develop a better definition of the MP released during CM and to study MP phenotypes in relation to clin ....Cerebral malaria (CM) is a life-threatening complication of infection caused by parasites. The mechanisms leading to coma, convulsions and death in CM remain unknown. CM in children is associated with high levels of endothelial microparticles (MP). However, not only the levels but also the phenotypes of MP can be altered in CM as well as their related functional properties. The project aims to develop a better definition of the MP released during CM and to study MP phenotypes in relation to clinical syndrome, disease severity and disease outcome.Read moreRead less
Prevalence, Nature And Recommendations For Clinical Management And Self-management Of Depression For People With HIV
Funder
National Health and Medical Research Council
Funding Amount
$470,290.00
Summary
By comparing the nature and prevalence of depression in those with and without HIV, and documenting the ways in which general practitioners manage depression in their patients, the project will provide a comprehensive and layered understanding of depression among men, particularly those living with HIV in urban and regional Australia. Project findings will develop the skills and research capacity of general practitioners in the assessment and management of depression.
Approaches to combat AIDS and its causative agent, the human immunodeficiency virus HIV-1, have thus far proved ineffective. The proposed research program intends to investigate the nuclear import of two HIV-1 proteins which have central roles in HIV infection. We will apply our expertise in the area of the regulation of nuclear import of viral proteins, and build on our observations with respect to these proteins to attempt to establish the mechanistic basis of their nuclear import, and how thi ....Approaches to combat AIDS and its causative agent, the human immunodeficiency virus HIV-1, have thus far proved ineffective. The proposed research program intends to investigate the nuclear import of two HIV-1 proteins which have central roles in HIV infection. We will apply our expertise in the area of the regulation of nuclear import of viral proteins, and build on our observations with respect to these proteins to attempt to establish the mechanistic basis of their nuclear import, and how this differs from the conventional nuclear import pathways used by normal cellular proteins. We already have evidence that nuclear import of HIV-Tat is regulated in novel fashion by cellular factors, and intend, through determining its mechanistic basis, to be able to form the basis of a strategy to block this import pathway specifically, and thereby inhibit HIV replication. This may form the basis in the future of a new pharmaceutical approach to combat HIV-AIDS.Read moreRead less
Targeting CD4-positive Cells For Anti-HIV Gene Therapy
Funder
National Health and Medical Research Council
Funding Amount
$356,646.00
Summary
Treatment of HIV early following infection is thought to be important for maximising the quality of life of patients. Conventional therapy has had some success in early intervention but resistance invariably develops. This application proposes to develop a gene therapy approach to elimiate HIV infected cells by introducing a suicide gene into those cells that harbor the virus. The advantage of this approach is the limited toxicity that is associated with gene therapies as well as the ability to ....Treatment of HIV early following infection is thought to be important for maximising the quality of life of patients. Conventional therapy has had some success in early intervention but resistance invariably develops. This application proposes to develop a gene therapy approach to elimiate HIV infected cells by introducing a suicide gene into those cells that harbor the virus. The advantage of this approach is the limited toxicity that is associated with gene therapies as well as the ability to target specific cell-types. It is proposed to genetically modify a strain of adenovirus to introduce a gene that will kill cells that it infects that also contain HIV. This is a novel approach and potentially may be an important treatment in the future. Anti-HIV gene therapy may also be useful in addition to the more conventional treatments.Read moreRead less
Assessment Of Alpha-galactosylceramide As A Novel Adjuvant For Pandemic Influenza: A Virua Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$220,042.00
Summary
The occurrence of human infections with pathogenic avian H5N1 Influenza A viruses was the first documentation of these viruses demonstrating an ability to directly transmit from birds to humans. The virulent nature of these infections, and the fact that there is no pre-existing immunity to these viruses in the human population has raised the concern that these viruses may emerge to cause the next influenza pandemic. Vaccination is our most effective way of protecting against influenza infection, ....The occurrence of human infections with pathogenic avian H5N1 Influenza A viruses was the first documentation of these viruses demonstrating an ability to directly transmit from birds to humans. The virulent nature of these infections, and the fact that there is no pre-existing immunity to these viruses in the human population has raised the concern that these viruses may emerge to cause the next influenza pandemic. Vaccination is our most effective way of protecting against influenza infection, however there are no commercially available avian influenza vaccines available. Moreover, recent evidence suggests current vaccines strategies may be less than effective. This proposal aims to evaluate the efficacy of a novel vaccine strategy that promotes immune protection against a potential pandemic influenza strain.Read moreRead less
Neonatal Immunization With Pneumococcal Conjugate Vaccine In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$1,181,966.00
Summary
One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the dev ....One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the development of immunity and response to other vaccines given to infants. This study will also provide a unique opportunity for training of PNG and Australian scientists in both countries; transfer state-of-the-art immunological technology and stimulate further collaborations on respiratory infections in the region.Read moreRead less
Understanding Factors Contributing To Nausea: Clinical And Patient Perspectives
Funder
National Health and Medical Research Council
Funding Amount
$100,000.00
Summary
This study aims to develop and validate indicators that can be used to more effectively identify nausea and its contributing factors in patients with advanced cancer receiving palliative care. Stage one involves a systematic review of the literature and qualitative interviews with patients and clinicians to identify clinical and psychosocial factors associated with nausea in the end stages of life. Stage 2 involves a study to evaluate the validity of the identified indicators in predicting patie ....This study aims to develop and validate indicators that can be used to more effectively identify nausea and its contributing factors in patients with advanced cancer receiving palliative care. Stage one involves a systematic review of the literature and qualitative interviews with patients and clinicians to identify clinical and psychosocial factors associated with nausea in the end stages of life. Stage 2 involves a study to evaluate the validity of the identified indicators in predicting patients’ experiences of nausea.Read moreRead less
An Evaluation Of The Validity Of Measureing Salivary Oxycodone Concentrations For Pharmacokinetic Studies In Patients
Funder
National Health and Medical Research Council
Funding Amount
$49,135.00
Summary
In many countries, oxycodone is replacing morphine as the opioid of first choice for the treatment of moderate to severe pain. Despite this, very little is known about how the drug is processed in the body or how its ability to control pain is affected by such factors as other drugs, age or organ function. Studies to determine this usually require multiple blood tests from individual patients over set time periods. Our team is able to measure drug levels in saliva and has shown this to be a vali ....In many countries, oxycodone is replacing morphine as the opioid of first choice for the treatment of moderate to severe pain. Despite this, very little is known about how the drug is processed in the body or how its ability to control pain is affected by such factors as other drugs, age or organ function. Studies to determine this usually require multiple blood tests from individual patients over set time periods. Our team is able to measure drug levels in saliva and has shown this to be a valid substitute for the measurement of drug levels in blood. Furthermore, one of us has developed a computer modelling system that shows how drugs are handled in the body using only a few samples from each patient. Palliative care patients are generally frail and unwell. We are reluctant to expose them to invasive tests such as repeated blood sampling. If we can prove that saliva sampling is as good as blood sampling, we will have identified a simple non-invasive means of greatly increasing our knowledge of oxycodone and how it behaves in individual patients. This in turn may allow us to tailor drug doses according to the unique characteristics of each patient and to optimise their pain control.Read moreRead less
Evidence For Psychological And-or Educational Interventions For Cancer-related Fatigue: A Systematic Review
Funder
National Health and Medical Research Council
Funding Amount
$28,283.00
Summary
Potential benefits to the community: Fatigue is one of the most common and distressing symptoms experienced by people with cancer and can exacerbate the experience of other symptoms, negatively affect mood, and impact on function and quality of life. Understanding which interventions are effective in helping people cope with cancer-related fatigue is important to inform decision-making by consumers, clinicians working in palliative care and policy makers. Objectives: This study aims to systemati ....Potential benefits to the community: Fatigue is one of the most common and distressing symptoms experienced by people with cancer and can exacerbate the experience of other symptoms, negatively affect mood, and impact on function and quality of life. Understanding which interventions are effective in helping people cope with cancer-related fatigue is important to inform decision-making by consumers, clinicians working in palliative care and policy makers. Objectives: This study aims to systematically review the evidence for psychological and-or educational interventions for managing cancer-related fatigue. Methods: This study will use the Cochrane Collaboration’s methodology to search, critically appraise, and analyse randomised controlled trials of psychological and-or educational interventions. This will involve collaboration with consumers and with the Cochrane Pain, Palliative Care, and Supportive Care Collaborative Review Group. This review will inform decision-making at all levels, assist in research translation and identify further gaps in the research regarding this distressing symptom.Read moreRead less