The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Small heat-shock molecular chaperone proteins and amyloid fibrils. This proposal addresses the fundamental mechanisms of protein aggregation associated with debilitating age-related diseases, e.g. Alzheimer's, Parkinson's and cataract, and the prevention of aggregation via the action of a group of molecular chaperone proteins known as small heat-shock proteins. With the ageing population, the prevalence of these diseases will increase significantly over the next 20 years. Understanding and treat ....Small heat-shock molecular chaperone proteins and amyloid fibrils. This proposal addresses the fundamental mechanisms of protein aggregation associated with debilitating age-related diseases, e.g. Alzheimer's, Parkinson's and cataract, and the prevention of aggregation via the action of a group of molecular chaperone proteins known as small heat-shock proteins. With the ageing population, the prevalence of these diseases will increase significantly over the next 20 years. Understanding and treating these diseases will therefore have significant long-term health benefits. Furthermore, the highly structured protein aggregates that form as hallmarks of many of these diseases have potential wide ranging applications in the emerging field of bionanotechnology, e.g. as nanowires and biofilms.Read moreRead less
Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and c ....Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and cutting-edge directed evolution methodologies. Intended outcomes include enhanced institutional capacity for interdisciplinary collaboration; discovery of fundamentally important bacterial sensors; and development of synthetic regulatory circuits enabling outgrowth of non-biological biocatalysis industries.Read moreRead less
Structural and functional characterisation of PI3Kgamma, uniquely activated by p101. The movement of cells is involved in all aspects of life including development, growth and maintenance of organisms. In spite of this, our understanding of the mechanism involved in cell migration is limited. There are a number of conditions in which the ability to control cell movement would be of significant benefit. Examples include autoimmune conditions, asthma and cancer, the social and economic burdens ....Structural and functional characterisation of PI3Kgamma, uniquely activated by p101. The movement of cells is involved in all aspects of life including development, growth and maintenance of organisms. In spite of this, our understanding of the mechanism involved in cell migration is limited. There are a number of conditions in which the ability to control cell movement would be of significant benefit. Examples include autoimmune conditions, asthma and cancer, the social and economic burdens of which account for billions of dollars and millions of Australians. This project aims to understand one of the major mechanisms that controls cell migration, which is expected to produce significant economic and social outcomes in the areas of basic science knowledge, human health, and biotechnology. Read moreRead less
Evolutionary origins of sexual parasitism in an Australian freshwater fish. Carp gudgeons are the most abundant, widespread and biodiverse freshwater fishes in southeastern Australia. The unacknowledged presence of many cryptic species and sexually-parasitic lineages severely taints all research on this cornerstone group. This project aims to provide unrivalled evolutionary, genomic, and taxonomic insights into this new instance of vertebrate sexual parasitism, which offers a unique mix of resea ....Evolutionary origins of sexual parasitism in an Australian freshwater fish. Carp gudgeons are the most abundant, widespread and biodiverse freshwater fishes in southeastern Australia. The unacknowledged presence of many cryptic species and sexually-parasitic lineages severely taints all research on this cornerstone group. This project aims to provide unrivalled evolutionary, genomic, and taxonomic insights into this new instance of vertebrate sexual parasitism, which offers a unique mix of research advantages not displayed by any other sexual/unisexual complex. The knowledge gained could impact many research fields, including evolutionary theory addressing the unexplainable prevalence of sex, native fish ecology, and environmental monitoring of the Murray-Darling Basin, an ecosystem of world significance.Read moreRead less
LIPID AND LIPOPROTEIN ADSORPTION AT BIOMATERIALS AND BIO-DIAGNOSTICS INTERFACES. This project aims to investigate molecular mechanisms involved in the formation of undesired biological deposits on synthetic materials and thereby help establish the scientific basis for the rational design of materials with improved compatibility with biological fluids and the engineering of a new generation of biomedical implant devices and bio-diagnostic devices. It is well known that proteins accumulate on synt ....LIPID AND LIPOPROTEIN ADSORPTION AT BIOMATERIALS AND BIO-DIAGNOSTICS INTERFACES. This project aims to investigate molecular mechanisms involved in the formation of undesired biological deposits on synthetic materials and thereby help establish the scientific basis for the rational design of materials with improved compatibility with biological fluids and the engineering of a new generation of biomedical implant devices and bio-diagnostic devices. It is well known that proteins accumulate on synthetic solid surfaces. This project proposes to investigate whether lipids and lipoproteins also play key roles in the initiation of biological adsorption processes. Combined with the study of the interfacial forces responsible, this information will guide the design of preventative strategies.Read moreRead less
Physico-chemical and Biopharmaceutical Investigations of Novel Drug Delivery Systems for Oral Administration of Lipophilic Drugs. The new platform technology for carrying lipophilic molecules will be applicable to many molecules currently under development by Australian Industry and will inspire novel encapsulation approaches to new and existing drugs as well as functional foods and nutraceuticals. Improved oral bioavailability of anticancer drugs will improve the quality of life of patients, re ....Physico-chemical and Biopharmaceutical Investigations of Novel Drug Delivery Systems for Oral Administration of Lipophilic Drugs. The new platform technology for carrying lipophilic molecules will be applicable to many molecules currently under development by Australian Industry and will inspire novel encapsulation approaches to new and existing drugs as well as functional foods and nutraceuticals. Improved oral bioavailability of anticancer drugs will improve the quality of life of patients, reduce health care costs and provide broader benefits to the community. The Australian biotechnology/pharmaceutical industries can share in a greater proportion of the US$50 billion market for specialised drug delivery, which is increasing by 20% annually. Australia's scientific competitiveness will be strengthened in the fields of nano-encapsulation and colloidal delivery.Read moreRead less
Safer gene editing tools for Australian livestock and biotech industries. Editing the genome of an organism in an efficient and safe fashion is critical for the livestock and biotechnology industries. While CRISPR-Cas9 has become the method of choice for genome editing, it is known to introduce unwanted "on-target" and "off-target" mutations, limiting its utility. To address this the CI team created a novel genome editing platform technology termed Crackling-CAST that is almost 100% accurate, w ....Safer gene editing tools for Australian livestock and biotech industries. Editing the genome of an organism in an efficient and safe fashion is critical for the livestock and biotechnology industries. While CRISPR-Cas9 has become the method of choice for genome editing, it is known to introduce unwanted "on-target" and "off-target" mutations, limiting its utility. To address this the CI team created a novel genome editing platform technology termed Crackling-CAST that is almost 100% accurate, while retaining the efficiency of the classical Cas9 system. This project will exemplify the capabilities of the novel gene targeting platform in cell types used by the biotechnology and livestock sectors, ensuring its global uptake by these industries and delivering significant economic benefits for Australia. Read moreRead less
Origins and distributions of intraplate earthquakes. This project aims to investigate the behaviour and origin of intraplate earthquakes in Australia by developing a multi-million-year record of earthquakes using geological, geochronological, geospatial, seismological, statistical and numerical modelling data. It will use maximum credible magnitudes, maximum shaking intensities of intraplate earthquakes and spatiotemporal relationships between large prehistoric and contemporary earthquakes to im ....Origins and distributions of intraplate earthquakes. This project aims to investigate the behaviour and origin of intraplate earthquakes in Australia by developing a multi-million-year record of earthquakes using geological, geochronological, geospatial, seismological, statistical and numerical modelling data. It will use maximum credible magnitudes, maximum shaking intensities of intraplate earthquakes and spatiotemporal relationships between large prehistoric and contemporary earthquakes to improve models of future seismic hazard in Australia and globally. This will lead to improved predictions of future earthquake impacts in urban and natural environments and development of new paleoseismic techniques.Read moreRead less
Building bio-inspired smart nanochannels for virus detection. This project aims to harness high-precision silicon nanofabrication methods to create the next generation of bio-inspired viral biosensors. The new technology would enable prompt, cost-efficient, and accurate detection of virus contamination of our water and food supplies. The project plans to fabricate arrays of parallel double-layered nanochannels in silicon via templated etching, with surface functionalisation to display receptors. ....Building bio-inspired smart nanochannels for virus detection. This project aims to harness high-precision silicon nanofabrication methods to create the next generation of bio-inspired viral biosensors. The new technology would enable prompt, cost-efficient, and accurate detection of virus contamination of our water and food supplies. The project plans to fabricate arrays of parallel double-layered nanochannels in silicon via templated etching, with surface functionalisation to display receptors. These nanochannels are designed to act as size-selective filters for electrochemical and electrochemiluminescence sensing. The project plans to explore innovative signal amplification and multiplexing capabilities for ultrasensitive detection of norovirus and bacteriophages.Read moreRead less