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
Understanding how dynamic changes in chromatin composition control genome function. DNA is tightly packaged in eukaryotic cells as chromatin. Important genetic processes, such as transcription, require manipulation of chromatin structure to access the DNA. The cell sets up specialised chromatin structures to regulate these processes. Currently, precise molecular details of these specialised structures are limited. This project will push the envelope of an in vitro model chromatin system and dete ....Understanding how dynamic changes in chromatin composition control genome function. DNA is tightly packaged in eukaryotic cells as chromatin. Important genetic processes, such as transcription, require manipulation of chromatin structure to access the DNA. The cell sets up specialised chromatin structures to regulate these processes. Currently, precise molecular details of these specialised structures are limited. This project will push the envelope of an in vitro model chromatin system and determine the architecture of several chromatin states with unique functional implications inside the cell. This will unravel the molecular instructions that define how our genomes are organised, significantly advancing our knowledge of fundamental eukaryotic genome biology and paving the way for the future development of new tools and therapies.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775570
Funder
Australian Research Council
Funding Amount
$570,000.00
Summary
Purchase of a high resolution organic mass spectrometer. The diverse research supported by the new instrument is expected to encompass a wide range of beneficial outcomes in the areas of health, plant genetics and breeding, horticulture, chemistry and novel analytical technologies. Genetic studies will lead to improved plant crops and are expected to contribute to new treatments for multiple scleroris and diabetes. Investigations in organic and organometallic chemistry will lead to the productio ....Purchase of a high resolution organic mass spectrometer. The diverse research supported by the new instrument is expected to encompass a wide range of beneficial outcomes in the areas of health, plant genetics and breeding, horticulture, chemistry and novel analytical technologies. Genetic studies will lead to improved plant crops and are expected to contribute to new treatments for multiple scleroris and diabetes. Investigations in organic and organometallic chemistry will lead to the production of better materials, more efficient catalysts and novel drugs. This instrument will provide infrastructure essential to enabling researchers to maintain internationally competitive profiles in these areas.Read moreRead less
Dissecting a RNA-histone variant interaction and its role in splicing. This project aims to define the molecular details of how a chromatin component, histone H2A.B, binds RNA and influences RNA splicing. This is unprecedented for histones, which are typically associated with DNA and transcriptional regulation. Over 90 per cent of human genes may be alternatively spliced. This explains how complex organisms develop from a limited set of genes, but how alternative splicing decisions are made is u ....Dissecting a RNA-histone variant interaction and its role in splicing. This project aims to define the molecular details of how a chromatin component, histone H2A.B, binds RNA and influences RNA splicing. This is unprecedented for histones, which are typically associated with DNA and transcriptional regulation. Over 90 per cent of human genes may be alternatively spliced. This explains how complex organisms develop from a limited set of genes, but how alternative splicing decisions are made is unclear. The intended outcome is to reveal links between chromatin, RNA splicing and gene expression regulation to explain how multicellular organisms have evolved. The translation of this knowledge will ultimately provide long-term economic and health benefits for Australia.Read moreRead less
Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specifi ....Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specific key genes deregulated in cancer, to correct their expression and stably reprogram the phenotype of the tumour cell in a normal-like state. It outlines the engineering of novel synthetic agents to block specific protein-protein interactions in cancer cells and to induce potent tumour cell death. This work will generate novel and selective therapeutics to treat un-curable forms of tumours.Read moreRead less
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
Cellular Gene Regulation Networks. The benefit to Australia will be scientific in terms of providing an understanding of how cells integrate transcriptional control systems and the networks that are involved. This will inform research on folate deficiency and aberrant human development and towards identifying genes that are important in improving efficiency of microbial fermentations. Additional and more practical major benefits will follow from the development of tools to analyse interaction ....Cellular Gene Regulation Networks. The benefit to Australia will be scientific in terms of providing an understanding of how cells integrate transcriptional control systems and the networks that are involved. This will inform research on folate deficiency and aberrant human development and towards identifying genes that are important in improving efficiency of microbial fermentations. Additional and more practical major benefits will follow from the development of tools to analyse interactions between control systems, including software of value to the research community. The work will provide postgraduate students with major training in up-to-date genomic technologies, and in the interface between application of bioinformatics and experimental science.
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I am a molecular geneticist with a primary focus on the identification of genes and sequence variants underlying susceptibility to, and progression of, various tumour types _ in particular tumours of the skin (moles and melanoma), oesophagus, ovary, lung
Senataxin, A Novel Protein Involved In The DNA Damage Response
Funder
National Health and Medical Research Council
Funding Amount
$500,460.00
Summary
The human genome is constantly exposed to agents-chemicals that cause DNA damage. Some of these are generated during normal metabolism and are referred to as reactive oxygen species while others comprise damaging sunlight, radiation and a variety of chemical agents. These agents can lead to cancer and a range of pathologies to different tissues including deterioration of brain function. This project is designed to investigate these processes using a specific genetic disorder as a model system. T ....The human genome is constantly exposed to agents-chemicals that cause DNA damage. Some of these are generated during normal metabolism and are referred to as reactive oxygen species while others comprise damaging sunlight, radiation and a variety of chemical agents. These agents can lead to cancer and a range of pathologies to different tissues including deterioration of brain function. This project is designed to investigate these processes using a specific genetic disorder as a model system. This disorder is called ataxia with oculomotor apraxia type 2 or AOA2. This condition develops in the teenage to early twenties and as the name suggests is characterised by loss of control of gait together with difficulties of eye movement. It is due to reduced function of a particular region of the brain called the cerebellum responsible for controlling movement. We have initial data suggesting that cells from these patients are very sensitive to environmental chemicals and their capacity to carry out repair of damage to DNA is compromised. We will investigate the nature of the defect at the molecular level and establish the function of the protein defective in this syndrome. This information will be important to determining specific therapies for AOA2 patients and may also have relevance to other neurodegenerative disorders.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775503
Funder
Australian Research Council
Funding Amount
$255,000.00
Summary
Robotics for plant genomics: Increasing throughput in plant genetic analyses. Plant genomics has direct benefit to crop improvement, especially as focussed in the applicants' laboratories. Thus, the Australian agri-food sector will benefit substantially from the acceleration in plant functional genomics that will arise from the installation of the robotics equipment described in the current application, by both underpinning more applied research and also being used directly in crop improvement p ....Robotics for plant genomics: Increasing throughput in plant genetic analyses. Plant genomics has direct benefit to crop improvement, especially as focussed in the applicants' laboratories. Thus, the Australian agri-food sector will benefit substantially from the acceleration in plant functional genomics that will arise from the installation of the robotics equipment described in the current application, by both underpinning more applied research and also being used directly in crop improvement programs such as are based at the Waite Campus. The outputs will include crops with increased tolerance to biotic and abiotic stresses, a reduced dependence on chemical inputs such as fertilisers and improved food quality, with consequent benefits to the environment and human health and nutrition.Read moreRead less