The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. Thi ....The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. This knowledge will help us understand the process of development in mammals, including birth defects in humans.Read moreRead less
Evolution of nervous system patterning processes: characterisation of homologs of key Drosophila regulatory genes from the coral Acropora. Defining the common mechanisms of nervous system development is one of the major goals of modern biology, but is presently being addressed largely by comparisons between a few very advanced (and therefore specialised) animals. Comparative data from a lower animal is urgently needed, and will clarify many aspects of nervous system evolution and development. Th ....Evolution of nervous system patterning processes: characterisation of homologs of key Drosophila regulatory genes from the coral Acropora. Defining the common mechanisms of nervous system development is one of the major goals of modern biology, but is presently being addressed largely by comparisons between a few very advanced (and therefore specialised) animals. Comparative data from a lower animal is urgently needed, and will clarify many aspects of nervous system evolution and development. The pioneering work carried out on Acropora in this laboratory suggests that it is perhaps the best choice currently available for this purpose. This project will use Acropora to address fundamental questions about the evolution of nervous system developmental processes.Read moreRead less
Manipulation of apoptosis-related genes to generate novel disease resistances in banana. Bananas are one of Australia's most important fruit crops. However, the industry is continually threatened by numerous diseases including yellow and black Sigatoka, Fusarium wilt and bunchy top. Control of these diseases currently requires either extensive pesticide treatments or complex agronomic procedures, of which most are ineffective, expensive or environmentally damaging. The aim of this project is to ....Manipulation of apoptosis-related genes to generate novel disease resistances in banana. Bananas are one of Australia's most important fruit crops. However, the industry is continually threatened by numerous diseases including yellow and black Sigatoka, Fusarium wilt and bunchy top. Control of these diseases currently requires either extensive pesticide treatments or complex agronomic procedures, of which most are ineffective, expensive or environmentally damaging. The aim of this project is to utilise a novel strategy to generate transgenic bananas with resistance to these diseases. The benefit will be both economic and environmental as implementation should significantly reduce or eliminate pesticide use. Importantly, this strategy can potentially be extrapolated to many other crops.Read moreRead less
Generating broad and stable resistance to gemini- and nanoviruses. The ssDNA geminiviruses and nanoviruses are considered a major threat to crop production in the tropics and subtropics. There are currently no effective control strategies for these viruses. We have been developing a novel transgenic strategy for generating resistance to ssDNA viruses based on the activation of a suicide gene in the presence of the viral Rep protein. Importantly, we have demonstrated proof-of-principle using Toba ....Generating broad and stable resistance to gemini- and nanoviruses. The ssDNA geminiviruses and nanoviruses are considered a major threat to crop production in the tropics and subtropics. There are currently no effective control strategies for these viruses. We have been developing a novel transgenic strategy for generating resistance to ssDNA viruses based on the activation of a suicide gene in the presence of the viral Rep protein. Importantly, we have demonstrated proof-of-principle using Tobacco yellow dwarf mastrevirus. In this project, we aim to further develop this strategy into a broad and stable mechanism for generating resistance to all known geminiviruses and nanoviruses.Read moreRead less
Unravelling the sub-nuclear complexity of the brain. Understanding the function of the brain is a major frontier of scientific research. The ability to increase knowledge of brain function is reliant upon the development of novel methods. This application will develop a novel approach for understanding the function of particular nerve cells. One outcome will be demonstration of the applicability of a novel method of benefit to all brain researchers. Another outcome will be increased understandin ....Unravelling the sub-nuclear complexity of the brain. Understanding the function of the brain is a major frontier of scientific research. The ability to increase knowledge of brain function is reliant upon the development of novel methods. This application will develop a novel approach for understanding the function of particular nerve cells. One outcome will be demonstration of the applicability of a novel method of benefit to all brain researchers. Another outcome will be increased understanding of one brain region that is known to contribute to the development of cardiovascular disease. It is expected that increased knowledge of brain function will lead to novel theories of brain disease and therapeutic strategies.Read moreRead less
Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million ....Origin of multicellularity in animals: identification and analysis of intercellular signalling pathways in a basal metazoan, the demosponge Reniera. The Reniera genome project is a multi-million dollar collaboration between JGI (US-DOE) and Australian scientists that will see the sequencing of the first Australian marine animal by 2006. This project will significantly advance our understanding of the origins of animals and contribute to the reconstruction of creatures that lived over 600 million years ago. A major outcome of this reconstruction will be a fundamental understanding of how cells communicate with each other during the process of development to give rise to the diversity of cell types within multicellular animals. This study will also shed light on what happens when cell communication goes astray, as observed in a range of human malignancies, including cancer. Read moreRead less
The biology of arbovirus virulence and fitness in arthropod and vertebrate hosts in vivo. In Australia, Ross River virus (RRV) represents significant concern to human health. Between 1992-2005 more than 50,000 notifications of RRV infection have been reported. While not fatal, the disease is responsible for morbidity in the community/individual that can have both social and economic costs. The project has several national benefits. It will help elucidate whether there is any association between ....The biology of arbovirus virulence and fitness in arthropod and vertebrate hosts in vivo. In Australia, Ross River virus (RRV) represents significant concern to human health. Between 1992-2005 more than 50,000 notifications of RRV infection have been reported. While not fatal, the disease is responsible for morbidity in the community/individual that can have both social and economic costs. The project has several national benefits. It will help elucidate whether there is any association between RRV strain and increased risk of RRV transmission and/or occurrence of more severe cases of human disease. It will help develop technologies that can lead towards the identification of viral markers, which could provide new avenues in the design of novel antiviral strategies.
Read moreRead less
Characterisation of interacting genes that condition avirulence and resistance between Phytophthora pathogens and soybean. Plant pathogens from the genus Phytophthora cause severe crop losses in Australia and worldwide. Resistance in host plants is frequently overcome by mutation of avirulence genes in the pathogen to create virulent new races. We will clone and characterise genes from Phytophthora sojae that control virulence and avirulence, and isolate soybean genes whose products interact w ....Characterisation of interacting genes that condition avirulence and resistance between Phytophthora pathogens and soybean. Plant pathogens from the genus Phytophthora cause severe crop losses in Australia and worldwide. Resistance in host plants is frequently overcome by mutation of avirulence genes in the pathogen to create virulent new races. We will clone and characterise genes from Phytophthora sojae that control virulence and avirulence, and isolate soybean genes whose products interact with the Phytophthora gene products. An understanding of the molecular mechanisms than enable current plant varieties to recognise Phytophthora pathogens leading to resistance or susceptibility will assist the development of novel strategies for durable disease resistance in soybean and other crop plants.Read moreRead less
The role of epigenetics in the early gestational programming of adult phenotype by ethanol. The concept of foetal programming is changing the way we think about the aetiology of complex disease in adults. Our studies would emphasise that adverse events during pregnancy can have long-term health implications, with concomitant social and economic consequences. In America, the prevalence of foetal alcohol syndrome is comparable with rates for Down syndrome. The Aboriginal community in Australia ....The role of epigenetics in the early gestational programming of adult phenotype by ethanol. The concept of foetal programming is changing the way we think about the aetiology of complex disease in adults. Our studies would emphasise that adverse events during pregnancy can have long-term health implications, with concomitant social and economic consequences. In America, the prevalence of foetal alcohol syndrome is comparable with rates for Down syndrome. The Aboriginal community in Australia has been identified as a high-risk group. The knowledge gained from this project could aid in the development of screening strategies to predict the likelihood of disease developing later in life, providing an opportunity for presymptomatic healthcare.Read moreRead less
Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of th ....Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of the establishment of epigenetic state, combined with its heritability during mitosis, provides all the essential components for developmental noise. If our hypothesis proves correct, our work will have a major impact on the understanding of one of the most basic concepts in genetics.Read moreRead less