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
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
Some of the world's most important diseases, including important diseases of indigenous chilren and the hospitalised elderly are caused by bacteria that carry a surface coating called a capsule. It is not clear how this capsule is retained by bacteria. Resolution of this question could lead to the development of new disinfectants that will stop hospital-acquired infections, to new reagents that can be incoporated into medical devices where bacteria frequently grow, and new antibiotics.
Molecular Basis Of O-antigen Modification And Genomics Of Serotype-converting Bacteriophages Of Shigella Flexneri
Funder
National Health and Medical Research Council
Funding Amount
$268,264.00
Summary
There are approximately 165 million cases of shigellosis world wide annually, resulting in 1.1 million deaths. The majority of cases occur in developing countries and most deaths occur in children under 5 years of age. Shigellosis is mainly caused by the bacterium Shigella flexneri. There are 13 different serotypes of S. flexneri determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses (bacteriophages) carry the genes which confer O-antigen variation. Infection a ....There are approximately 165 million cases of shigellosis world wide annually, resulting in 1.1 million deaths. The majority of cases occur in developing countries and most deaths occur in children under 5 years of age. Shigellosis is mainly caused by the bacterium Shigella flexneri. There are 13 different serotypes of S. flexneri determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses (bacteriophages) carry the genes which confer O-antigen variation. Infection and subsequent incorporation of the virus into the genetic material of the bacterial cell result in modification of the bacterial O-antigen. This phage-mediated O-antigen modification gives rise to different serotypes. The project will address fundamental processes related to the O-antigen modification. This will be achieved by studying structure and function of the enzymes encoded by the O-antigen modification gene cluster. We have isolated several serotype-converting bacteriophages from S. flexneri and we plan to compare and characterise their genomic information to increase understanding of their origin and relationship with the bacterial host.Read moreRead less
Development Of Early Warning Systems For Dengue Fever Based On Socio-ecological Factors
Funder
National Health and Medical Research Council
Funding Amount
$327,402.00
Summary
Global climate change has potentially serious effects on the transmission of dengue. An early warning system (EWS) based on socio-ecological factors will be developed to examine where and when outbreaks of dengue are likely to occur and how the future dengue control strategies and prevention efforts need to be applied and strengthened in Australia. This project will provide a platform for future research on developing and implementing an EWS for dengue in the Asia-Pacific region.
Population Dynamics And Evolution Of Mosquitoes That Transmit Malaria
Funder
National Health and Medical Research Council
Funding Amount
$381,807.00
Summary
Population dynamics and evolutionary process are fundamental to mosquito-borne infectious diseases as evolutionary forces steer both mosquito and malaria parasite to evolve around obstacles in their natural development. Environmental and ecological factors also influence the relationship between mosquito, parasite and humans. Therefore control of mosquito borne disease depends on an innate understanding of the genetics, behavior and environment. Thus studies on mosquito population dynamics inclu ....Population dynamics and evolutionary process are fundamental to mosquito-borne infectious diseases as evolutionary forces steer both mosquito and malaria parasite to evolve around obstacles in their natural development. Environmental and ecological factors also influence the relationship between mosquito, parasite and humans. Therefore control of mosquito borne disease depends on an innate understanding of the genetics, behavior and environment. Thus studies on mosquito population dynamics including population densities, migration, population subdivisions and competition for resources will allow an understanding of these relationships. Island populations of malaria transmitting mosquitoes contain less genetic complexity (genetic variation in mosquito subpopulations) than mainland populations. Thus mosquito island populations may not contain the genetic capability of evolving around detrimental selection pressures such as the use of insecticides or predators. Armed with accurate knowledge of genetic complexity, biology and behavior of mosquito disease vector species, control measures can be accurately focused at specific populations (high disease transmission mosquito populations). This project we will identify specific populations of mosquitoes using their DNA to reveal genetic markers for specific behavior traits. Due to the smaller amount of genetic variations that island mosquito populations contain, and our aquired knowledge of their behavior and biology. We will design focused mosquito control strategies with knowledge that the mosquitoes will have a smaller chance of evolving around these control measures.Read moreRead less