Molecular machines that drive microbial pathogens. We will provide a comprehensive understanding of molecular machines situated at the surface of bacteria. This ground-breaking research will provide excellent outcomes in the training of research students and staff: this project entails frontier technology, and the transfer of technological capabilities not currently available in Australia. Our study on a non-pathogenic species of bacteria is timely too for National security: related species of b ....Molecular machines that drive microbial pathogens. We will provide a comprehensive understanding of molecular machines situated at the surface of bacteria. This ground-breaking research will provide excellent outcomes in the training of research students and staff: this project entails frontier technology, and the transfer of technological capabilities not currently available in Australia. Our study on a non-pathogenic species of bacteria is timely too for National security: related species of bacteria were amongst the first organisms trialed as biological weapons, and the pathogenic species remain rated as Class 3 organisms by the Centers for Disease Control.Read moreRead less
Mitochondrial biogenesis: the evolution of molecular machines. Benefits from this research program fall into two discrete types. Firstly, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the development of skills not common in Australia. Secondly, detailed knowledge will be gained of molecular machines and the way in which they may differ in human cells and in the cells of human cell parasites, with im ....Mitochondrial biogenesis: the evolution of molecular machines. Benefits from this research program fall into two discrete types. Firstly, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the development of skills not common in Australia. Secondly, detailed knowledge will be gained of molecular machines and the way in which they may differ in human cells and in the cells of human cell parasites, with implications for the treatment of human disease.Read moreRead less
Reducible complexity in the molecular machines of humans and bacteria. Firstly, we will provide detailed knowledge of the surface membrane proteins of an important class of bacteria, the alpha-proteobacteria. Secondly, excellent outcomes are provided for the training of postgraduate students and research staff: this project entails frontier technology, and the transfer of technological capabilities not currently available in Australia. Thirdly, our studies on non-pathogenic species of alpha-prot ....Reducible complexity in the molecular machines of humans and bacteria. Firstly, we will provide detailed knowledge of the surface membrane proteins of an important class of bacteria, the alpha-proteobacteria. Secondly, excellent outcomes are provided for the training of postgraduate students and research staff: this project entails frontier technology, and the transfer of technological capabilities not currently available in Australia. Thirdly, our studies on non-pathogenic species of alpha-proteobacteria is timely for National security: species of alpha-proteobacteria were amongst the first organisms trialled as biological weapons by the USA and the former Soviet Union, and these pathogenic species remain rated as Class 3 organisms by the Centers for Disease Control. Read moreRead less
Regulated Shuttling Of Beta-catenin And IQGAP1 Between Nucleus And Plasma Membrane In Migrating Cells
Funder
National Health and Medical Research Council
Funding Amount
$511,703.00
Summary
Inherited gene mutations that cause colon cancer kill 4,700 Australians every year. About 1 in 21 Australians develop colorectal cancer by age 75. Activation of the beta-catenin protein is a critical switch in the path to colon cancer. We discovered that beta-catenin, and another protein it interacts with called IQGAP1, move between different cellular compartments. We plan to study this process in more detail, as it relates to how beta-catenin works and to understanding its role in cancer.
Structural Basis Of Ligand Binding To Type 1 Insulin-like Growth Factor Receptor (IGF-1R)
Funder
National Health and Medical Research Council
Funding Amount
$446,562.00
Summary
Insulin-like growth factors are involved in normal growth and development. However, they are also implicated in cancer development and progression. We are seeking to understand the way in which these growth factors bind to their receptor on the surface of the cell and stimulate the cell to survive, proliferate and migrate to new tumour sites. Such knowledge will be useful in the design of molecules that could potentially intervere with this process and thus be used as anti-cancer therapeutics.
Membrane Proteins within the Mouse Transcriptome- Annotation of their Organisation and Subcellular Localisation. A major issue in cell biology today is how distinct regions of the cell maintain their unique composition of proteins. The aim of this grant is to identify membrane proteins within the mouse genome and annotate their localisation within the cell. Our multi-discipline effort will combine extensive computational prediction strategies with focused cellular biology experimental determinat ....Membrane Proteins within the Mouse Transcriptome- Annotation of their Organisation and Subcellular Localisation. A major issue in cell biology today is how distinct regions of the cell maintain their unique composition of proteins. The aim of this grant is to identify membrane proteins within the mouse genome and annotate their localisation within the cell. Our multi-discipline effort will combine extensive computational prediction strategies with focused cellular biology experimental determination. The underpinning experimental technology, termed reverse transfection arrays, allows for high-throughput assessment of cellular phenotype properties for individual proteins.Read moreRead less
Spatio-temporal modelling of Ras dependent MAP kinase activation. This project is at the heart of the national research priority 'Frontier Technologies for Building and Transforming Australian Industries'. Using cutting edge methods and techniques of systems biology, coupled with innovative experimental molecular cell biology we will construct and simulate mathematical models of the EGF-regulated MAP kinase pathway. The project will yield new insights into the fundamental mechanisms of cell sign ....Spatio-temporal modelling of Ras dependent MAP kinase activation. This project is at the heart of the national research priority 'Frontier Technologies for Building and Transforming Australian Industries'. Using cutting edge methods and techniques of systems biology, coupled with innovative experimental molecular cell biology we will construct and simulate mathematical models of the EGF-regulated MAP kinase pathway. The project will yield new insights into the fundamental mechanisms of cell signal transduction that drive cell division, differentiation and transformation and may enable the design of new anticancer therapies. Importantly, the modelling and simulation methods developed in the project will have a general applicability to other complex systems such as sustainable ecological systems.Read moreRead less
Covalent Hydrogen Bond Mimetics of Helical Peptide Hormones. Peptide hormones have been identified that adopt a helical shape when bound to their receptor. The project will produce new versions of these hormones by the use of directly bonded chemical linkers in place of the relatively weak helix hydrogen bonds. The resulting hormone mimics will be more stable, have lower molecular weight and be more selective than the natural hormones making them more suitable as drugs. Our new chemical techn ....Covalent Hydrogen Bond Mimetics of Helical Peptide Hormones. Peptide hormones have been identified that adopt a helical shape when bound to their receptor. The project will produce new versions of these hormones by the use of directly bonded chemical linkers in place of the relatively weak helix hydrogen bonds. The resulting hormone mimics will be more stable, have lower molecular weight and be more selective than the natural hormones making them more suitable as drugs. Our new chemical techniques allow us for the first time to fully investigate this approach which if successful will be applicable to many other helical peptides and therefore could be an important drug development technique.Read moreRead less
A new G-protein coupled receptor target for conotoxins. We aim to understand the interaction between venom components from the marine cone snail, a major source of potential drug leads, and a key receptor in nerve cell signalling. This receptor plays a role in many nervous system functions and has been proposed as a target for treating a range of diseases including pain, depression and drug addiction. It is critical that we understand this interaction so we can fully exploit the potential of the ....A new G-protein coupled receptor target for conotoxins. We aim to understand the interaction between venom components from the marine cone snail, a major source of potential drug leads, and a key receptor in nerve cell signalling. This receptor plays a role in many nervous system functions and has been proposed as a target for treating a range of diseases including pain, depression and drug addiction. It is critical that we understand this interaction so we can fully exploit the potential of these molecules as drug leads. The potential exists for multibillion dollar markets for these new drugs that could provide significant economic benefits to Australia.Read moreRead less
Common hot spots in protein-activated GPCRs enable discovery of new ligands for mapping of G-protein signalling pathways. This project will teach researchers and industry how to more rapidly discover new compounds for development into medicines, and how to design them with reduced side effects. This interdisciplinary research will provide excellent training for scientists in chemistry, pharmacology, biochemistry and biotechnology. It will advance fundamental science at the chemistry-biology inte ....Common hot spots in protein-activated GPCRs enable discovery of new ligands for mapping of G-protein signalling pathways. This project will teach researchers and industry how to more rapidly discover new compounds for development into medicines, and how to design them with reduced side effects. This interdisciplinary research will provide excellent training for scientists in chemistry, pharmacology, biochemistry and biotechnology. It will advance fundamental science at the chemistry-biology interface, attract international interest from researchers, students, and companies, with potential for translational and commercial outcomes. New drug leads and information on how important drug targets communicate with different intracellular signalling pathways has potential to impact on National Research Priorities of good health and building Australian industry.Read moreRead less