RadioGenes2: Modelling complex biomolecular interactions in radiated tumours: Towards understanding the genesis of therapeutic radioresistance. About 45% of bladder cancer patients require radiotherapy or surgery. Radiotherapy has a failure rate of ~50%. Surgery (bladder removal) diminishes quality of life considerably. Modelling complex gene interactions in radiated cancer cells will provide crucial knowledge on the molecular genesis of radiotherapy-resistance of tumours. Our findings will prov ....RadioGenes2: Modelling complex biomolecular interactions in radiated tumours: Towards understanding the genesis of therapeutic radioresistance. About 45% of bladder cancer patients require radiotherapy or surgery. Radiotherapy has a failure rate of ~50%. Surgery (bladder removal) diminishes quality of life considerably. Modelling complex gene interactions in radiated cancer cells will provide crucial knowledge on the molecular genesis of radiotherapy-resistance of tumours. Our findings will provide: (i) an accurate mathematical/computational model for diagnosing radiosensitivity; (ii) further insights to be applied in the pharmaceutical sector such as the discovery of novel molecular targets that have the potential to increase radiotherapy success ratios; (iii) a holistic modelling technique applicable to a larger diversity of tumours.Read moreRead less
Electric field induced surface attachment and detachment of proteins. Microarrays are revolutionising the diagnosis of disease by enabling large amounts of data on genetics and protein expression to be obtained from one sample. Biosensors for diseases and toxins rely on the same mechanism, namely attachment of biological macromolecules to a surface. We propose a new method for controlling the attachment by micromachining an electrode system to apply an electric field to chosen sites. Ultimately ....Electric field induced surface attachment and detachment of proteins. Microarrays are revolutionising the diagnosis of disease by enabling large amounts of data on genetics and protein expression to be obtained from one sample. Biosensors for diseases and toxins rely on the same mechanism, namely attachment of biological macromolecules to a surface. We propose a new method for controlling the attachment by micromachining an electrode system to apply an electric field to chosen sites. Ultimately microelectronic engineering methods will be used. This will give control over the attachment process with potential benefits of orienting attaching molecules, minimising non-specific attachment and enriching diagnostics by enabling interrogation of the force of attachment.Read moreRead less
Devil Facial Tumour Disease: Cytogenetic Clues to Transmission and Development. Devil Facial Tumour Disease is a fatal cancer that is decimating Tasmanian devils. Preliminary work suggests that tumours from different animals have identical sets of highly abnormal chromosomes, including a giant marker chromosome. We will use DNA probes to 'paint' abnormal tumour chromosomes to discover markers for diagnosis, and identify genes contributing to tumour development and immune suppression. Most import ....Devil Facial Tumour Disease: Cytogenetic Clues to Transmission and Development. Devil Facial Tumour Disease is a fatal cancer that is decimating Tasmanian devils. Preliminary work suggests that tumours from different animals have identical sets of highly abnormal chromosomes, including a giant marker chromosome. We will use DNA probes to 'paint' abnormal tumour chromosomes to discover markers for diagnosis, and identify genes contributing to tumour development and immune suppression. Most importantly, we will test our hypothesis that tumours all arose from a single ancestral cancer cell that is transmitted between animals. A cellular transmission has frightening implications for spread of disease, but will allow us to develop appropriate therapeutic strategies to save a unique Australian marsupial from extinction.Read moreRead less
The development of a rapid diagnostic test for heparanase activity. Heparanase is an enzyme that has been implicated in a number of disease states such as cancer, arthritis, multiple sclerosis and other inflammatory diseases. Characterisation of this enzyme has been slow, due in part to the lack of a reliable direct activity assay. Using a multi-disciplinary approach, this project seeks to establish a rapid assay that will provide easy determination of heparanase activity. Furthermore, this a ....The development of a rapid diagnostic test for heparanase activity. Heparanase is an enzyme that has been implicated in a number of disease states such as cancer, arthritis, multiple sclerosis and other inflammatory diseases. Characterisation of this enzyme has been slow, due in part to the lack of a reliable direct activity assay. Using a multi-disciplinary approach, this project seeks to establish a rapid assay that will provide easy determination of heparanase activity. Furthermore, this assay could provide a useful diagnostic tool in a clinical environment that would allow for the rapid assessment of these diseases, their progression and indeed response to therapy.Read moreRead less
Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in bi ....Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in biotechnology. The ultimate aim is to create novel technologies for protein production, modification and analysis that will accelerate the pace of discovery in protein research, basic cell and organism biology, diagnostics, biotechnology and drug discovery. Read moreRead less
Molecular approaches to solving current and emerging problems in the epidemiology and diagnosis of Marek's disease in Australia. Marek's disease (MD) is a ubiquitous viral disease of chickens that is currently controlled in meat chickens by blanket vaccination of all chickens. However, as has happened overseas, the efficacy of the HVT vaccine being used in Australia is breaking down resulting in subclinical and clinical losses due to MD. To assist industry deal with this situation we propose to ....Molecular approaches to solving current and emerging problems in the epidemiology and diagnosis of Marek's disease in Australia. Marek's disease (MD) is a ubiquitous viral disease of chickens that is currently controlled in meat chickens by blanket vaccination of all chickens. However, as has happened overseas, the efficacy of the HVT vaccine being used in Australia is breaking down resulting in subclinical and clinical losses due to MD. To assist industry deal with this situation we propose to develop novel molecular methods for the quantification of Marek's disease viruses (MDV) in the host and the environment, to use these methods to design effective early monitoring systems for MD in broilers that predict disease and performance outcomes, and to develop an epidemiological model that will predict the spread and severity of MD as failure of vaccinal protection progresses.Read moreRead less
Why is most of the genetic variance for complex traits undetected by large powerful screens of common variants? The genomics revolution has made it possible to measure thousands of DNA variants in individuals. These variants have been associated with phenotypic outcomes in a range of species. Paradoxically, even very large studies have only accounted for a fraction of the resemblance between relatives that we know exist. Our study will test three specific hypotheses to explain this paradox. A be ....Why is most of the genetic variance for complex traits undetected by large powerful screens of common variants? The genomics revolution has made it possible to measure thousands of DNA variants in individuals. These variants have been associated with phenotypic outcomes in a range of species. Paradoxically, even very large studies have only accounted for a fraction of the resemblance between relatives that we know exist. Our study will test three specific hypotheses to explain this paradox. A better understanding about the genetic architecture for complex traits will improve the efficiency of gene mapping methods, including applications in humans for traits related to productive ageing and a healthy start to life, will lead to more efficient selection programs in agricultural populations and will inform us with respect to past evolutionary events.Read moreRead less
The multiplexed diagnosis of arbovirus infections using combinatorial probes. Viruses that cause serious diseases such as hemorrhagic fever or encephalitis must be quickly identified. Diagnostic tests based on DNA hybridisation are accurate and can be rapid but they are expensive. We will test a method for simplifying DNA tests and increasing their capabilities. DNA probes for detecting arboviruses will be designed at the ANU using new bioinformatic methods and their reliability will be model ....The multiplexed diagnosis of arbovirus infections using combinatorial probes. Viruses that cause serious diseases such as hemorrhagic fever or encephalitis must be quickly identified. Diagnostic tests based on DNA hybridisation are accurate and can be rapid but they are expensive. We will test a method for simplifying DNA tests and increasing their capabilities. DNA probes for detecting arboviruses will be designed at the ANU using new bioinformatic methods and their reliability will be modelled using all the available genetic information. Computer predictions will be experimentally tested in the PANBIO laboratory by using the probes to detect viral nucleic acids. The influence of virus genome complexity will be investigatedRead moreRead less
Detection of imported exotic strains of West Nile virus for national biosecurity surveillance. West Nile virus (WNV) is transmitted by mosquitoes and causes a fatal disease of the brain in animals and humans. WNV is currently exotic to this country, however a closely related, but benign cousin of this virus (Kunjin) can be found in Northern Australia. Currently it is very difficult to differentiate between infections with WNV and Kunjin using standard laboratory tests, therefore it will be diff ....Detection of imported exotic strains of West Nile virus for national biosecurity surveillance. West Nile virus (WNV) is transmitted by mosquitoes and causes a fatal disease of the brain in animals and humans. WNV is currently exotic to this country, however a closely related, but benign cousin of this virus (Kunjin) can be found in Northern Australia. Currently it is very difficult to differentiate between infections with WNV and Kunjin using standard laboratory tests, therefore it will be difficult for public health officials to detect WNV if it is introduced to Australia. In this project we aim to develop more accurate laboratory tests to detect infections with the deadly, exotic WNV using new strategies. Read moreRead less
Biomolecular activity modulated by interaction with nanostructures. Nanotechnological methods are able to reliably fabricate artificial nanostructures with dimensions similar to those of large biomolecules (a few to tens of nanometers). This study focuses on the interaction of artificial nanostructures with biomolecules such as proteins and DNA, and will enable scientists to better understand biomolecular recognition and binding events, which are central to all biological processes. The underst ....Biomolecular activity modulated by interaction with nanostructures. Nanotechnological methods are able to reliably fabricate artificial nanostructures with dimensions similar to those of large biomolecules (a few to tens of nanometers). This study focuses on the interaction of artificial nanostructures with biomolecules such as proteins and DNA, and will enable scientists to better understand biomolecular recognition and binding events, which are central to all biological processes. The understanding gained can then be used to design biomimetic surfaces for use in health monitoring and medical diagnostic devices with improved sensitivity, robustness and portability, thereby providing significant benefits to the health sector.Read moreRead less