Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A b ....Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A better understanding of gene regulation in malaria parasites will help us to better combat the tricks utilised by this and other organisms to elude our immune systems.Read moreRead less
A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We hav ....A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We have shown that Neurospora, like other less tractable multicellular eukaryotes, is tolerant of sequence mismatch, allowing high resolution analysis of individual recombination events. This project will build on fundamental advances we have already made in understanding how recombination occurs.Read moreRead less
Controlling the rate of transcription and translation of Rubisco transgenes effectively in higher-plant plastids. Genetic transformation of the circular genome of the plastids provides a containable means for modifying plant growth by manipulating photosynthesis. Although the transformation mechanism is precise, predicting the level of foreign gene expression is difficult because the amounts of messenger RNA and protein produced by foreign genes in plastids varies widely, even when the protein a ....Controlling the rate of transcription and translation of Rubisco transgenes effectively in higher-plant plastids. Genetic transformation of the circular genome of the plastids provides a containable means for modifying plant growth by manipulating photosynthesis. Although the transformation mechanism is precise, predicting the level of foreign gene expression is difficult because the amounts of messenger RNA and protein produced by foreign genes in plastids varies widely, even when the protein assembles without difficulty. This project will devise strategies for controlling this variability that will facilitate attempts to exploit plastid transformation for transplanting better versions of the photosynthetic CO2-fixing enzyme, Rubisco, into plants to improve their growth efficiency in terms of water, fertiliser and light use.Read moreRead less
Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the ....Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the controlled release of therapeutic compounds. The involvement of Honours and Ph.D students in this project will expose the next generation of Australian scientists to this emerging discipline. International collaboration leading to publications in high impact scientific journals will enhance Australia's scientific reputation.Read moreRead less
Genetics of longevity and the delay of post-reproductive senescence. Ageing of the population in the coming decades will cause an increasing health care burden. Diseases of ageing such as Alzheimer's, heart disease, Parkinson's and a range of cancers, as well as impairments of ageing such as reduced mobility and cognitive ability are all caused or exacerbated by oxidative stress. With some exceptions, current medical practices focus on surgical repair or drug therapy to alleviate symptoms of ag ....Genetics of longevity and the delay of post-reproductive senescence. Ageing of the population in the coming decades will cause an increasing health care burden. Diseases of ageing such as Alzheimer's, heart disease, Parkinson's and a range of cancers, as well as impairments of ageing such as reduced mobility and cognitive ability are all caused or exacerbated by oxidative stress. With some exceptions, current medical practices focus on surgical repair or drug therapy to alleviate symptoms of ageing rather than addressing the physiological causes of ageing itself. Our project will provide understanding of natural systems that prevent age-related senescence due to oxidative stress. The goal is to identify novel and natural ways to maximise the fitness, well-being and self-sufficiency of people as they age.Read moreRead less
Programming of appetite and bodyweight by the interaction of maternal diet and angiotensin during peri-natal life. The project describes a phenotype for appetite and body weight that can be altered by maternal dietary omega-3 PUFA (environmental factors), at a critical period during peri-natal life (developmental phase) and that the effect on body weight is opposite when endogenous angiotensin is increased (hormonal factor). The project aims to discover how these different factors interact to p ....Programming of appetite and bodyweight by the interaction of maternal diet and angiotensin during peri-natal life. The project describes a phenotype for appetite and body weight that can be altered by maternal dietary omega-3 PUFA (environmental factors), at a critical period during peri-natal life (developmental phase) and that the effect on body weight is opposite when endogenous angiotensin is increased (hormonal factor). The project aims to discover how these different factors interact to produce the phenotype by defining the critical period and systematically identifying genes that are expressed during this period. The effect of manipulating maternal dietary omega-3 PUFA and the role of angiotensin will then be examined. The project will discover how genetic, hormonal and environmental factors interact during the perinatal period of life to program food intake and body weight in adult life. Read moreRead less
Characterisation of tumour variants of Devil Facial Tumour Disease. This project will take a new approach to cancer research by studying the evolution of Devil Facial Tumour Disease. The results will directly contribute to the conservation management of the Tasmanian devil, as well as generating new information on tumour growth, metastasis and emergence of resistance.
Defining the earliest events in lymphatic vasculature formation from veins. Vascular system development is one of the earliest events that occurs in the embryo. The entire lymphatic vascular system forms from the embryo’s early veins. This project aims to define the earliest molecular and cellular changes essential to form an entire second vessel network from just a few precursor cells in the embryo. The project aims to utilise zebrafish and mouse embryos to greatly expand knowledge in the forma ....Defining the earliest events in lymphatic vasculature formation from veins. Vascular system development is one of the earliest events that occurs in the embryo. The entire lymphatic vascular system forms from the embryo’s early veins. This project aims to define the earliest molecular and cellular changes essential to form an entire second vessel network from just a few precursor cells in the embryo. The project aims to utilise zebrafish and mouse embryos to greatly expand knowledge in the formation of this essential vertebrate tissue. Ultimately, this is expected to provide new knowledge in stem and precursor cell differentiation, the evolution of complex organ systems and tissue formation. Outcomes may impact on future biotechnology in the areas of tissues engineering, stem cell differentiation and regeneration.Read moreRead less
Beyond the genome: unravelling the intricacies of epigenetic regulation using the honey bee model. Epigenetic mechanisms, such as DNA methylation, provide the interface between genome and environment. Abnormalities in epigenetic regulation lead to cancer and other diseases. The project will be using the alternative phenotypes in honeybees, fertile queens and sterile workers, to understand how dietary factors control conditional gene expression by methylation
Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisa ....Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisation or decay to control development. RNA-driven processes program morphogenesis and differentiation of spermatids, but via mechanisms only poorly understood. Uncovering the function of extensive cytoplasmic polyadenylation, which is essential for murine fertility, may fuel the next wave of RNA biotech applications. Read moreRead less