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
Gene Based Treatment Strategies For Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$2,630,000.00
Summary
Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project ....Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project aims to develop a potentially permanent solution to alleviate diabetes-related blindness in the world. The project combines several very recent scientific advances into one strategy to combat diabetic retinopathy at a molecular level. Vision is our most important sensory organ that cannot be replaced. Thus, human trials can only be conducted following extensive animal safety and efficacy trials. To date the development of new therapies has been seriously hampered by the lack of appropriate, easy to reproduce animal models for different stages of diabetic retinopathy. In addition, it aims to identify new therapeutic agents from molecules that are naturally produced by the retina while fighting the disease. Finally, tested and evaluated in the animal models. The most successful therapeutic candidates will then be further developed for human trials.If successful, our approach will potentially have a major impact on the treatment of diabetic retinopathy and possibly on all diabetic vascular diseases. A single injection might only be necessary to prevent the development of diabetic retinopathy, which would represent a significant weapon in the management of patients. In addition, successful application of secretion gene therapy in the eye might open up the possibility to introduce the same concept for the treatment of larger organs undergoing microvascular changes as a result of diabetes.Read moreRead less
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
Safety Of Hendra Virus Anti-G Glycoprotein Monoclonal Antibody In Humans
Funder
National Health and Medical Research Council
Funding Amount
$400,000.00
Summary
Hendra virus infection in humans is a serious, and often fatal, disease. No cure exists for Hendra infection and existing treatments are ineffective. Recently, a human monoclonal antibody has shown great promise in protecting animals from developing the disease. This project aims to perform preclinical safety testing and a Phase I clinical trial to establish the safety profile of this antibody such that it can be used to prevent Hendra infection in humans exposed to the disease.
Alternative Medicines From Medicinal Plants Of Aboriginal People Of Northern New South Wales
Funder
National Health and Medical Research Council
Funding Amount
$150,400.00
Summary
This research will conserve customary Australian Aboriginal knowledge of historical and cultural significance and apply this knowledge to the discovery of new evidence-based alternative medicines that may help address the growing need for new antimicrobial treatments. It will also be a model for collaboration between Australian Aboriginal communities and research scientists. The customary (traditional and contemporary) knowledge of medicinal plants possessed by Indigenous peoples is a significan ....This research will conserve customary Australian Aboriginal knowledge of historical and cultural significance and apply this knowledge to the discovery of new evidence-based alternative medicines that may help address the growing need for new antimicrobial treatments. It will also be a model for collaboration between Australian Aboriginal communities and research scientists. The customary (traditional and contemporary) knowledge of medicinal plants possessed by Indigenous peoples is a significant medicinal resource, as seen by the reliance on customary medicines by ~80% of the population in developing countries as their primary healthcare. There has been a renewed interest in customary medicines, especially with the increase in microbial resistance and emergence of new diseases, side effects of single compound medications and high cost of drug development. Australian Aboriginal people have a vast medicinal plant knowledge based on thousands of years of using plants as medicines. This especially includes topical use for conditions indicative of microbial infections. Despite their potential, relatively few studies have been conducted on Australian Aboriginal medicines to provide evidence for their use. For Northern New South Wales (NNSW) Aboriginal communities, as is the case for many other Australian Aboriginal communities, this customary knowledge is rapidly disappearing, especially due to premature deaths of the elder custodians of this knowledge. The overall aims of this project are to work in partnership with the NNSW Yaegl Local Aboriginal Land Council and Ulgundahi Elders Aboriginal Corporation to i) document and preserve first hand customary medicinal plant knowledge; ii) identify plants of significant medicinal potential in treating antibacterial and antifungal infections; iii) evaluate their effectiveness using in vitro and in vivo biological assays; and iv) identify the major bioactive components responsible for their medicinal properties.Read moreRead less
Use Of The Norfolk Island Genetic Isolate For Disease Gene Mapping
Funder
National Health and Medical Research Council
Funding Amount
$978,500.00
Summary
This gene mapping study will use a unique founder effect population to investigate two major public health disorders. We aim to identify genes that play a role in migraine and in cardiovascular disease, using a population from Norfolk Island. The Norfolk Island community is a population of ~1200 permanent residents, the majority of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake a full genome scan to identify migraine gene loci and QTL ....This gene mapping study will use a unique founder effect population to investigate two major public health disorders. We aim to identify genes that play a role in migraine and in cardiovascular disease, using a population from Norfolk Island. The Norfolk Island community is a population of ~1200 permanent residents, the majority of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake a full genome scan to identify migraine gene loci and QTL that influence cardiovascular disease using samples from this population isolate.Read moreRead less
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
Mapping Genes For Typical Migraine Using Twin Families.
Funder
National Health and Medical Research Council
Funding Amount
$439,124.00
Summary
Current evidence suggests multiple genes may underlie susceptibility to the more common forms of migraine. The project will look to see if the these genes provide clues to the further elucidation of the complex molecular pathways of migraine and will help in the development of diagnostic tests and evidence-based treatment strategies.