Blindness exerts major physical, emotional and economic constraints and hardship upon the sufferer. Transplant surgery can restore vision to many people who are visually impaired as a result of disease affecting the front of the eye. The transplant itself is taken from the eye of a person who has died, after consent from the donor's family. Our goal is to improve the outcome for patients who require transplants of tissue to the front of the eye, in order to restore their vision or to relieve pai ....Blindness exerts major physical, emotional and economic constraints and hardship upon the sufferer. Transplant surgery can restore vision to many people who are visually impaired as a result of disease affecting the front of the eye. The transplant itself is taken from the eye of a person who has died, after consent from the donor's family. Our goal is to improve the outcome for patients who require transplants of tissue to the front of the eye, in order to restore their vision or to relieve pain. Our work is predicated on the finding that unwanted immune responses are the major cause of graft failure in such patients. The recipient recognizes the grafted tissue as being foreign, and rejects it. Treatment with conventional systemic drugs appears to hold little promise for further improvements in outcome, but gene therapy applied to the donor tissue may provide a safe and effective way of reducing transplant failure. Gene therapy can be undertaken on the donor tissue in the laboratory, prior to transplantation surgery. In this project, we will assess the suitability of a new method of modifying the transplant. All of the work will be performed on the laboratory bench, or in experimental animals.Read moreRead less
Emotionally traumatic experiences are well remembered and, in some instances, frequent reminders of these events can lead to the development of fear-related anxiety disorders such as phobia or post-traumatic stress disorder (PTSD). The experiments outlined in this proposal will examine how a novel epigenetic mechanism of gene regulation contributes to the transition from the retrieval of a fear memory to its inhibition through a process called extinction.
Substandard Bed Nets And Malaria: Causes, Impact And Solutions
Funder
National Health and Medical Research Council
Funding Amount
$827,057.00
Summary
Long-lasting insecticidal nets (LLIN) are a cornerstone of malaria control. LLIN undergo strict testing overseen by WHO and are subject to inspections prior to delivery to recipient countries. Despite this, we found that LLINs delivered to Papua New Guinea (PNG) between 2013 and 2019 were ineffective against malaria mosquitoes. Concurrently we observed a massive rise in malaria in PNG. This study is aimed at understanding the causes and impact of substandard LLINs on the global malaria burden.
In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extende ....In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extended periods. We intend to test the ability of this vaccine to persist and persistently produce effective CD8 T cells not only systemically in the blood system but also at mucosal surfaces, where HIV usually gains entry during sexual intercourse.Read moreRead less
Role Of The Area Postrema In Determining The Increased Cardiac Sympathetic Nerve Activity In Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$489,912.00
Summary
In heart failure there is a large increase in sympathetic nerve activity to the heart that has detrimental effects on the heart and can induce sudden death. The areas in the brain causing the increased nerve activity are unknown. We will investigate the role of the area postrema, which is a window to the brain for hormones in the blood. We have evidence that this brain site maintains the high level of nerve activity in heart failure, possibly stimulated by hormones circulating in the blood.
Transgenic Expression Of The EWS-WT1 Fusion Protein,inducing The Development Of Tumour That Replicates The Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$112,976.00
Summary
A genetic translocation encoding the EWS-WT1 fusion protein is found desmoplastic small round cell tumours. Our aim is to examine the effect of this protein in inducing tumour growth in tissue cell lines. A virus will then be used to introduce the genetic translocation into mice to examine the effect of this protein on tumour growth in a mammal, thereby serving as a 'solid tumour model' to try and identify therapeutic targets.
Evaluation And Comparison Of Lentiviral And AAV Vector Mediated Gene Therapy For The Mucopolysaccharidoses
Funder
National Health and Medical Research Council
Funding Amount
$521,320.00
Summary
The mucopolysaccharidoses are a group of inherited diseases that have profound consequences for affected individuals. They have pleiotropic effects and usually result in premature death. Although intravenous enzyme replacement therapy has been developed for a number of these disorders, this approach to therapy is invasive, very expensive, of limited efficacy, and is completely ineffective in treating brain pathology. The principal reason for this is the protected nature of the brain which preven ....The mucopolysaccharidoses are a group of inherited diseases that have profound consequences for affected individuals. They have pleiotropic effects and usually result in premature death. Although intravenous enzyme replacement therapy has been developed for a number of these disorders, this approach to therapy is invasive, very expensive, of limited efficacy, and is completely ineffective in treating brain pathology. The principal reason for this is the protected nature of the brain which prevents enzymes that are administered intravenously from entering. Therefore, alternative therapies must be considered in order to provide more effective therapy for the mucopolysaccharidoses, especially those that have significant brain pathology. Gene therapy is one such alternative therapy but this still faces the problem of introducing the therapeutic agent (in this case the gene encoding the requisite enzyme) into the brain. This project aims to provide a comparitive evaluation of two gene therapy vectors for their efficacy in treating all aspects of the pathology found in the mucopolysaccharidoses. Both vectors have the properties of being able to efficiently deliver genes to different cell types and result in the stable genetic modification of the target cell, making them ideal for long-term treatment. However, for effective gene therapy, significant and widely distributed gene delivery to the brain, as well as to other tissues, will be required. This project aims to compare the efficacy of these vectors in two different animal models of the mucopolysaccharidoses that exhibit a wide range of the clinical problems associated with these diseases, importantly including brain pathology.Read moreRead less
Dengue is the leading mosquito-borne virus causing morbidity and mortality in the tropics. North Queens land has a history of dengue outbreaks, with 5 outbreaks in the last 3 years. Queensland Health has developed a Dengue Fever Management Plan for north Queensland that has had considerable success in preventing small outbreaks of dengue from developing into large epidemics. The cornerstone of this plan is the application of residual insecticide inside premises near dengue cases to kill the mosq ....Dengue is the leading mosquito-borne virus causing morbidity and mortality in the tropics. North Queens land has a history of dengue outbreaks, with 5 outbreaks in the last 3 years. Queensland Health has developed a Dengue Fever Management Plan for north Queensland that has had considerable success in preventing small outbreaks of dengue from developing into large epidemics. The cornerstone of this plan is the application of residual insecticide inside premises near dengue cases to kill the mosquito vector, Aedes aegypti, before it can spread the virus. While this method is effective, it is labor intensive, requires the cooperation of homeowners who may find it intrusive and exposes nontarget insects and animals to insecticide. We propose to develop a lure and kill strategy to improve the efficacy of vector control while minimising the exposure of nontarget animals. Several chemicals have been identified as highly attractive to dengue mosquitoes. Among these are extracts from water infusions of grass that are highly attractive to egg-laying mosquitoes and emanations from human skin that attract host-seeking mosquitoes. We will develop traps incorporating a. mosquito attractants and b. a killing agent to selectively control Ae. aegypti mosquitoes. These will be collectively called lethal traps. This project will employ the following approach towards the development of a lure and kill strtaegy for dengue control a. determine which compounds are most attractive to north Queensland Ae. aegypti in a laboratory wind tunnel; b. confirm the attraction of these compounds using sticky traps in the field; c. conduct field trials of candidate lethal traps to determine the spacing and density of traps needed to control mosquitoes d. conduct a large field trial to examine the efficacy of the optimised lure and kill strategy. We will also conduct ecological studies on aging and the flight range of Ae. aegypti to enhance the development of the strategy.Read moreRead less