Structure and dynamics of a multiprotein-mRNA complex involved in the regulation of gene expression. RNA/protein interactions are now recognised as a major control point in the regulation of gene-expression. Proteins such as HuR and the poly(C)-binding proteins (PCBPs) act to stabilise and transport specific messenger (m)RNAs, and thus determine their translation levels. In contrast to such an important function, very little is known about these protein/mRNA interactions at an atomic level. The ....Structure and dynamics of a multiprotein-mRNA complex involved in the regulation of gene expression. RNA/protein interactions are now recognised as a major control point in the regulation of gene-expression. Proteins such as HuR and the poly(C)-binding proteins (PCBPs) act to stabilise and transport specific messenger (m)RNAs, and thus determine their translation levels. In contrast to such an important function, very little is known about these protein/mRNA interactions at an atomic level. The current study will investigate the structural and biophysical properties of a recently discovered HuR/PCBP/mRNA complex implicated in the regulation of androgen receptor expression. This information has the potential to assist in the development of drugs to reduce AR expression in prostate cancer.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
Protein-mRNA interactions and their role in post-transcriptional regulation. The research outcomes will be of fundamental importance in the field of gene regulation, and as such will result in publications in high-profile international journals and continue to contribute to Australia's outstanding international reputation in biological research. Students and research associates that have the opportunity to work on this project will be trained in the use of state-of-the art technologies in bioche ....Protein-mRNA interactions and their role in post-transcriptional regulation. The research outcomes will be of fundamental importance in the field of gene regulation, and as such will result in publications in high-profile international journals and continue to contribute to Australia's outstanding international reputation in biological research. Students and research associates that have the opportunity to work on this project will be trained in the use of state-of-the art technologies in biochemistry, scientific rigour and presentation skills and thus contribute to the quality of our national workforce. Furthermore, applications that arise from this work will contribute to Australia's intellectual property and future development of biotechnological industry.Read moreRead less
Biologically-Inspired Recognition and Processing in Colloidal Systems. The proposed research will enhance the understanding of forces and adsorption in biologically-inspired synthetic systems, and thereby create new strategies for improving selective adsorption, stabilization, coagulation, and separation. The expected outcomes are: increased understanding of chiral interactions at surfaces, a technique for rapid measurement of surface selectivity, new and better agents for chiral separation, a ....Biologically-Inspired Recognition and Processing in Colloidal Systems. The proposed research will enhance the understanding of forces and adsorption in biologically-inspired synthetic systems, and thereby create new strategies for improving selective adsorption, stabilization, coagulation, and separation. The expected outcomes are: increased understanding of chiral interactions at surfaces, a technique for rapid measurement of surface selectivity, new and better agents for chiral separation, a reduction in the use of organic pollutants, new methods for colloidal processing that will enable the preparation of new materials, and new surface coatings for increasing the useful life-time of medical implants.Read moreRead less
New approaches to inhibition of activity of HIV integrase. This project aims to assist in the development of novel anti-HIV drugs that will benefit the 17000 Australians and more than 33 million people worldwide who are currently suffering with this terrible disease. The project will utilise state-of-the-art approaches in structure-based drug design to identify and synthesise compounds as leads for the development of anti-HIV drugs. Furthermore, the project will provide invaluable training for t ....New approaches to inhibition of activity of HIV integrase. This project aims to assist in the development of novel anti-HIV drugs that will benefit the 17000 Australians and more than 33 million people worldwide who are currently suffering with this terrible disease. The project will utilise state-of-the-art approaches in structure-based drug design to identify and synthesise compounds as leads for the development of anti-HIV drugs. Furthermore, the project will provide invaluable training for the researchers involved and enhance the relationship between the academic and commercial collaborators.Read moreRead less
Optimisation of peptidic non-phosphorylated inhibitors of the Grb7 SH2 domain. The research outcomes will be of fundamental importance in the field of inhibitor development and as such will result in publications in high-profile international journals and continue to contribute to Australia's outstanding international reputation in biological research. Students and research associates that have the opportunity to work on this project will be trained in the use of state-of-the art technologies in ....Optimisation of peptidic non-phosphorylated inhibitors of the Grb7 SH2 domain. The research outcomes will be of fundamental importance in the field of inhibitor development and as such will result in publications in high-profile international journals and continue to contribute to Australia's outstanding international reputation in biological research. Students and research associates that have the opportunity to work on this project will be trained in the use of state-of-the art technologies in biochemistry, scientific rigour and presentation skills and thus contribute to the quality of our national workforce. Furthermore, applications that arise from this work will contribute to Australia's intellectual property and future developments in the pharmaceutical industry.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560722
Funder
Australian Research Council
Funding Amount
$512,744.00
Summary
High-speed Ultracentrifuge Facility with Sensitive Scanning Optics for the Analysis of Interacting Biomolecules. This request is for a high-speed analytical ultracentrifuge equipped with sensitive absorbance, fluorescence, and interference scanning optics. The equipment, the first of its kind in Australia, would establish a world-class facility for analysing the size, shape, and stability of macromolecular complexes and their interactions in solution. This new facility will enable high through ....High-speed Ultracentrifuge Facility with Sensitive Scanning Optics for the Analysis of Interacting Biomolecules. This request is for a high-speed analytical ultracentrifuge equipped with sensitive absorbance, fluorescence, and interference scanning optics. The equipment, the first of its kind in Australia, would establish a world-class facility for analysing the size, shape, and stability of macromolecular complexes and their interactions in solution. This new facility will enable high through-put screening of small molecules with potential as new drugs. This core platform technology will cover the range of needs from basic research through to commercialization of discovery. The equipment will support existing high quality research projects in biotechnology and provide new opportunities for post-graduate training and international collaboration.Read moreRead less
DsbA: A target for the design of drug candidates as selective inhibitors of oxidative protein folding in Gram negative bacteria. There is a clear need for development of novel antibiotics which are capable of treating the increasingly prevalent strains of pathogenic bacteria that are resistant to currently available drugs. In this proposal we will design novel inhibitors of bacterial enzymes that are required for the correct folding of a variety of proteins and test the effects of these molecule ....DsbA: A target for the design of drug candidates as selective inhibitors of oxidative protein folding in Gram negative bacteria. There is a clear need for development of novel antibiotics which are capable of treating the increasingly prevalent strains of pathogenic bacteria that are resistant to currently available drugs. In this proposal we will design novel inhibitors of bacterial enzymes that are required for the correct folding of a variety of proteins and test the effects of these molecules on enzyme activity, bacterial growth and antibiotic resistance. Specific inhibitors of these enzymes constitute a novel strategy for the treatment of bacteria that have developed resistance to existing antimicrobial drugs.
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Protein-protein interactions in amyloid deposits. The aggregation of specific proteins to form insoluble amyloid fibrils is characteristic of several age-related diseases such as type-II diabetes, Alzheimer's disease and Parkinson's disease. In vivo amyloid deposits also contain three prominent non-fibrillar protein components, namely serum amyloid P component, apolipoprotein E and alpha1-antichymotrypsin. These non-fibrillar amyloid components bind to a wide variety of amyloid fibrils, irresp ....Protein-protein interactions in amyloid deposits. The aggregation of specific proteins to form insoluble amyloid fibrils is characteristic of several age-related diseases such as type-II diabetes, Alzheimer's disease and Parkinson's disease. In vivo amyloid deposits also contain three prominent non-fibrillar protein components, namely serum amyloid P component, apolipoprotein E and alpha1-antichymotrypsin. These non-fibrillar amyloid components bind to a wide variety of amyloid fibrils, irrespective of the nature of the protein constituent. This proposal is to identify the structural basis for this recognition process, the capacity of non-fibrillar components to cross-link amyloid fibrils to form networks and the influence of these interactions on amyloid fibril cytotoxicity.Read moreRead less