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Mechanisms of chronic infection, immunotolerance and coevolution in avian circovirus infections. This project will generate fundamental new knowledge into the pathogenesis of persistent, chronic viral diseases in a wide range of animal hosts. Furthermore, beak and feather disease virus is listed as a Key Threatening Process under the Endangered Species Protection Act (1992) to at least sixteen endangered Australian bird species. Very little is known about the host-virus interactions that occur d ....Mechanisms of chronic infection, immunotolerance and coevolution in avian circovirus infections. This project will generate fundamental new knowledge into the pathogenesis of persistent, chronic viral diseases in a wide range of animal hosts. Furthermore, beak and feather disease virus is listed as a Key Threatening Process under the Endangered Species Protection Act (1992) to at least sixteen endangered Australian bird species. Very little is known about the host-virus interactions that occur during the early stages of infection or why some birds recover yet others develop full blown disease. This project will provide new knowledge that can be used to counteract its effects on current and future endangered species recovery program.Read moreRead less
Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stick ....Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stickiness of malaria parasites to blood vessels. Our project will tackle the conditions of MP production and define new drugs to prevent it. It also will explain how the brain becomes affected by high numbers of MP. Our results will cast new light on why the brain functions abnormally when its blood vessels become modified.Read moreRead less
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as l ....Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as least as effective as current drugs. This project will combine recent developments in stabilisation and cellular trapping of platinum(IV) pro-drugs with a range of strategies designed to limit activation of these pro-drugs to the tumour environment.Read moreRead less
A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a ....A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a role in the development of diabetes in humans. In plants, sugars affect many processes including growth, flowering, photosynthesis, nitrogen metabolism, starch synthesis, pigmentation and response to pathogens.Read moreRead less
An investigation of respiration in stuttering. Australia leads the world in stuttering research, and this project will maintain that profile. The research aims to establish if breathing has a causal role in stuttering. The new knowledge produced will support or weaken current theories of the cause of stuttering and will contribute to understanding the nature of the disorder. In particular, it will be applied to develop more effective and efficient treatments for chronic stuttering.
Establishing the relationship between anxiety and stuttering. The present project will establish basic knowledge about the disorder of stuttering, which will contribute to offsetting the personal and community costs of the disorder by guiding empirical investigations into its nature and the development of future treatments. Further benefits at the population level will occur by provision to the public of basic information about the disorder assembled from this project. By conveying information f ....Establishing the relationship between anxiety and stuttering. The present project will establish basic knowledge about the disorder of stuttering, which will contribute to offsetting the personal and community costs of the disorder by guiding empirical investigations into its nature and the development of future treatments. Further benefits at the population level will occur by provision to the public of basic information about the disorder assembled from this project. By conveying information from the present project to clinicians who treat stuttering patients, the project will benefit Australians who stutter.Read moreRead less
Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood for ....Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood formation will be studied. We will establish techniques for several steps that will be useful for all zebrafish mapping projects. We expect the genetic characterization of these mutants to provide new insights into nerve cell survival, gut development, and blood formation.Read moreRead less
Children with speech impairment: A population study of prevalence, severity, impact and service provision. Compared to the general community, adults who had a speech impairment as a child typically achieve lower levels of education, have greater literacy problems, experience significant social problems and discrimination, and have decreased occupational opportunities. The social and economic cost of untreated speech impairment for individuals, schools and society is large. This landmark study wi ....Children with speech impairment: A population study of prevalence, severity, impact and service provision. Compared to the general community, adults who had a speech impairment as a child typically achieve lower levels of education, have greater literacy problems, experience significant social problems and discrimination, and have decreased occupational opportunities. The social and economic cost of untreated speech impairment for individuals, schools and society is large. This landmark study will identify strengths and limitations in the health and education sectors regarding appropriate and holistic services for children with speech impairment combining identified prevalence, severity and impact data.Read moreRead less
Molecular control of embryonic patterning: The function of Rhou gene in mediating response to WNT signalling. The scientific knowledge gained from this investigation of the early development of embryos will inform us of how the essential building blocks of the body are assembled, and provide insights into the genetic and developmental causes of birth defects. This will benefit the health professionals, the research community, the education sector and the general public, by underpinning the form ....Molecular control of embryonic patterning: The function of Rhou gene in mediating response to WNT signalling. The scientific knowledge gained from this investigation of the early development of embryos will inform us of how the essential building blocks of the body are assembled, and provide insights into the genetic and developmental causes of birth defects. This will benefit the health professionals, the research community, the education sector and the general public, by underpinning the formulation of new research hypotheses, enriching the curriculum and the provision of informed counselling. The embryological expertise developed for this project will enhance the nation's research capability through the sharing of skills and knowledge with a national network of academic and industrial research teams. Read moreRead less