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
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
Copper Radiopharmaceuticals for Molecular Imaging of Alzheimer's Disease. The expected outcome of this research is to develop molecular agents to allow non-invasive diagnostic imaging of senile plaques associated with the onset of Alzheimer's disease. This will contribute to a better understanding of the disease, assist in early diagnosis and help assess new intervention strategies. Alzheimer's disease is the most common form of dementia and affects over 160,000 Australians. The imaging agent ma ....Copper Radiopharmaceuticals for Molecular Imaging of Alzheimer's Disease. The expected outcome of this research is to develop molecular agents to allow non-invasive diagnostic imaging of senile plaques associated with the onset of Alzheimer's disease. This will contribute to a better understanding of the disease, assist in early diagnosis and help assess new intervention strategies. Alzheimer's disease is the most common form of dementia and affects over 160,000 Australians. The imaging agent market is a niche biotechnology industry in which Australia already has an international presence. The proposed research will lead to innovations to ensure Australia remains internationally competitive in this area. This research has potential social and economic benefits for the nation.Read moreRead less
Probing the function of protein molecular motors on nano-fabricated structures. The function of protein linear molecular motors, which are natural dynamic bio-nano-devices with a ubiquitous importance in multicellular organisms, will be 'probed' with purposefully designed nano-structures fabricated via photo- or Scanning Probe Microscopy Lithography, that is, flat polymeric surfaces with combinatorial combinations of physico-chemistries; and micro/nano-channels and nano-wells with critical dimen ....Probing the function of protein molecular motors on nano-fabricated structures. The function of protein linear molecular motors, which are natural dynamic bio-nano-devices with a ubiquitous importance in multicellular organisms, will be 'probed' with purposefully designed nano-structures fabricated via photo- or Scanning Probe Microscopy Lithography, that is, flat polymeric surfaces with combinatorial combinations of physico-chemistries; and micro/nano-channels and nano-wells with critical dimensions similar to the scale of the probed biomolecules. The project turns 'up-side down' the challenge of invasive nano-probing of biomolecules using it in an engineered manner. The fundamental understanding of linear molecular motors will impact on biomedical science and on the assessment of hybrid natural-artificial dynamic nano-devices.Read moreRead less
Exploiting the self-assembly of hydrophobin proteins to engineer functional nanostructuring surfaces. There is an increasing world-wide demand for advanced nano-biomaterials with novel properties. We will use natural hydrophobin proteins to coat nanodevices and make them more compatible with biological systems. Hydrophobin coatings will be applicable to biosensors, medical devices, diagnostics and drug delivery systems. The research will lead to an understanding of the basic mechanisms of protei ....Exploiting the self-assembly of hydrophobin proteins to engineer functional nanostructuring surfaces. There is an increasing world-wide demand for advanced nano-biomaterials with novel properties. We will use natural hydrophobin proteins to coat nanodevices and make them more compatible with biological systems. Hydrophobin coatings will be applicable to biosensors, medical devices, diagnostics and drug delivery systems. The research will lead to an understanding of the basic mechanisms of protein self-assembly and will have application outcomes that contribute to Australia being an important player in the field of nanotechnology. This is critical for Australia's long term competitiveness and productivity in and beyond the 21st century.Read moreRead less
Opto-Microfluidics: A Rapid and Sensitive Platform for Biological Diagnostics. One in four people above 25 years suffer from diabetes-related diseases in Australia, with an associated economic cost exceeding $3 billion a year. A microdevice for continuous glucose monitoring would help patients to manage the disease, leading to huge individual, clinical and societal benefits. Life expectancy is expected to increase along with quality of life. Integration of the microdevice with insulin delivery w ....Opto-Microfluidics: A Rapid and Sensitive Platform for Biological Diagnostics. One in four people above 25 years suffer from diabetes-related diseases in Australia, with an associated economic cost exceeding $3 billion a year. A microdevice for continuous glucose monitoring would help patients to manage the disease, leading to huge individual, clinical and societal benefits. Life expectancy is expected to increase along with quality of life. Integration of the microdevice with insulin delivery would realise an 'artificial pancreas', revolutionising the management and treatment of the disease. The technology will also provide a platform for other point-of-care medical diagnostic devices, which will allow early participation in this emerging market and cement Australia's position in bionanotechnology.Read moreRead less
In-situ Scanning Probe Microscopy of biological redox processes: nanoscale structure and morphology. The science behind this project underpins the development of nanobiotechnology. Immediate applications foreseen, are the development of biosensors and diagnostic devices based on our intimate knowledge of the nature of the protein attachment to a surface. Use of synthetic membranes to create biomimetic surfaces will impact significantly on our understanding of the role and contribution membranes ....In-situ Scanning Probe Microscopy of biological redox processes: nanoscale structure and morphology. The science behind this project underpins the development of nanobiotechnology. Immediate applications foreseen, are the development of biosensors and diagnostic devices based on our intimate knowledge of the nature of the protein attachment to a surface. Use of synthetic membranes to create biomimetic surfaces will impact significantly on our understanding of the role and contribution membranes have on protein structure, function hence disease.Read moreRead less
Simulating two-phase electrodynamic flows in droplet-based microfluidic circuit elements. The knowledge, data and analysis tools developed within this project will facilitate the economical production of electrodynamically controlled integrated droplet-based microfluidic devices for critical high-demand applications such as: genome sequencing; protein evolution, synthesis and crystallisation; micro-structured pharmaceuticals; disposable devices for biomedical analysis; portable point-of-entry (b ....Simulating two-phase electrodynamic flows in droplet-based microfluidic circuit elements. The knowledge, data and analysis tools developed within this project will facilitate the economical production of electrodynamically controlled integrated droplet-based microfluidic devices for critical high-demand applications such as: genome sequencing; protein evolution, synthesis and crystallisation; micro-structured pharmaceuticals; disposable devices for biomedical analysis; portable point-of-entry (biochem)security analysis devices. Hence this project is an investment in enabling technologies to benefit Australia's growing biotech, pharmaceutical and micro/nanotechnology sectors. Tangible community benefits (e.g., in improved diagnostic technologies, pharmaceuticals) will result.Read moreRead less
Construction and Use of Yoctowells as Vessels for Catalysis, Sensing and Artificial Photosynthesis. Yoctowell recognition systems are likely to form the basis of a new generation of biosensors, high throughput screening systems for identification of nucleotides and as energy transduction systems. As a result, this research will be relevant to technological advances in the areas of biotechnology and nanotechnology. Researching functional yoctowells containing photoactive and redox-active componen ....Construction and Use of Yoctowells as Vessels for Catalysis, Sensing and Artificial Photosynthesis. Yoctowell recognition systems are likely to form the basis of a new generation of biosensors, high throughput screening systems for identification of nucleotides and as energy transduction systems. As a result, this research will be relevant to technological advances in the areas of biotechnology and nanotechnology. Researching functional yoctowells containing photoactive and redox-active components will contribute to the major effort in basic research on smart optoelectric that are needed today to meet tomorrow's energy demands in a sustainable way. Read moreRead less
Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less