Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882295
Funder
Australian Research Council
Funding Amount
$225,000.00
Summary
X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic re ....X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic research and collaborations with industry, which will enhance Australia's profile and commercialisation of research. The facility will enhance the usage of the Australian synchrotron, producing flagship projects on the edge of technical possibilities.Read moreRead less
Mammalian histidine kinase: its characterisation and role in hepatic cellular proliferation. Protein kinases regulate all aspects of cellular metabolism, but there is a class of protein kinase, histidine kinases, which exists in mammalian cells, about which remarkably little is understood. This project will be the first detailed characterisation of such an enzyme and investigation of its cellular function. The enzyme to be characterised is hepatic and it has been implicated in the regulation of ....Mammalian histidine kinase: its characterisation and role in hepatic cellular proliferation. Protein kinases regulate all aspects of cellular metabolism, but there is a class of protein kinase, histidine kinases, which exists in mammalian cells, about which remarkably little is understood. This project will be the first detailed characterisation of such an enzyme and investigation of its cellular function. The enzyme to be characterised is hepatic and it has been implicated in the regulation of DNA replication in regenerating liver. We shall obtain a detailed picture of the role of this histidine kinase in liver cell biology and an insight into the more general biological role of this class of enzyme.Read moreRead less
A global approach to structure, assembly and function of yeast mitochondrial ATP synthase. ATP synthase is responsible for the synthesis of the ubiquitous energy substance ATP in living cells. This multisubunit enzyme complex is a molecular rotatory motor whose mechanism relies on functional dynamic interactions of the component protein subunits of the complex. Using a combination of powerful and sophisticated molecular biology techniques the functional and dynamic contacts made by subunits wi ....A global approach to structure, assembly and function of yeast mitochondrial ATP synthase. ATP synthase is responsible for the synthesis of the ubiquitous energy substance ATP in living cells. This multisubunit enzyme complex is a molecular rotatory motor whose mechanism relies on functional dynamic interactions of the component protein subunits of the complex. Using a combination of powerful and sophisticated molecular biology techniques the functional and dynamic contacts made by subunits within the complex, or between ATP synthase and other enzyme complex involved in energy production (including other ATP synthase complexes) will be investigated. New and significant insights into one of the most fundamental and challenging enzymes of life will be obtained.Read moreRead less
The Structure Function and Biology of Serpins. The serpin family of proteins control protease activity, in a variety of biological systems, via a dramatic conformational change. We are 4 leaders in the serpin reseacrh field using an integrated approach of biochemistry, biophysics, molecular biology, cell biology, structural biology and bioinformatics to analyse every facet of serpin structure, function and biology. We will apply and develop novel technologies that will determine how these confor ....The Structure Function and Biology of Serpins. The serpin family of proteins control protease activity, in a variety of biological systems, via a dramatic conformational change. We are 4 leaders in the serpin reseacrh field using an integrated approach of biochemistry, biophysics, molecular biology, cell biology, structural biology and bioinformatics to analyse every facet of serpin structure, function and biology. We will apply and develop novel technologies that will determine how these conformational changes are achieved and how they are controlled. Our increased understanding of this inhibitor - enzyme interaction will have implications to other proteins which undergo conformational change and biotechnology.Read moreRead less
Structural and functional studies on prokaryote serpins. Proteins are the machines of life, many of which undergo complex movements to achieve function. The basic research described in this proposal will result in major outcomes in understanding how proteins fold, undergo complex changes in conformation, and misfold to dysfunctional states. As a result, the study will contribute fundamental knowledge that will underpin research in the fields of structural biology, protein design and protein fo ....Structural and functional studies on prokaryote serpins. Proteins are the machines of life, many of which undergo complex movements to achieve function. The basic research described in this proposal will result in major outcomes in understanding how proteins fold, undergo complex changes in conformation, and misfold to dysfunctional states. As a result, the study will contribute fundamental knowledge that will underpin research in the fields of structural biology, protein design and protein folding. Through providing insight into protein misfolding, the work will will contribute to our understanding of degenerative misfolding pathologies that affect the ageing population and thus targets the 'ageing well ageing productively' priority goal.Read moreRead less
Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. ....Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. Knowledge about this new aspect of protein degradation could provide a powerful tool to test the effect of the stabilisation or removal of specific proteins in the cell and also to develop new technologies in protein production.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0214135
Funder
Australian Research Council
Funding Amount
$492,000.00
Summary
High performance protein crystallography. This proposal will provide state of the art high performance facilities for protein crystallography, bringing together the major structural biology groups in NSW and the ACT. A renewed focus on protein crystal structures will stimulate new interpretation and utilization of the vast amount of data that has come from genomics, especially the sequencing of the human genome. The proposed facility will generate new research collaborations between the partn ....High performance protein crystallography. This proposal will provide state of the art high performance facilities for protein crystallography, bringing together the major structural biology groups in NSW and the ACT. A renewed focus on protein crystal structures will stimulate new interpretation and utilization of the vast amount of data that has come from genomics, especially the sequencing of the human genome. The proposed facility will generate new research collaborations between the partner institutions which will result in advances in basic life sciences, biotechnology and biopharmaceuticals. The facility will complement regional initiatives in functional genomics, bioinformatics, proteomics and high-field NMR spectroscopy.Read moreRead less
Mitochondrial proteases and their contribution to protein homeostasis. This research will examine how a critically important cellular organelle known as the mitochondrion maintains its functional integrity by sensing and signalling protein perturbations. As mitochondrial dysfunction is central to a number of neurodegenerative diseases understanding the molecular biology of this fundamentally important cellular process could, in the future, provide for better health outcomes for an aging Australi ....Mitochondrial proteases and their contribution to protein homeostasis. This research will examine how a critically important cellular organelle known as the mitochondrion maintains its functional integrity by sensing and signalling protein perturbations. As mitochondrial dysfunction is central to a number of neurodegenerative diseases understanding the molecular biology of this fundamentally important cellular process could, in the future, provide for better health outcomes for an aging Australian population. The training of post-graduate students is an integral component of this study and thus will contribute to building national research capacity. International collaborations and new discoveries will also contribute to the recognition of Australian research.Read moreRead less
Snapshots of an enzyme in action: structural and mechanistic studies on the catalytic cycle of Escherichia coli ketol-acid reductoisomerase. Enzymes are required for almost every process that occurs in a living organism. For this reason, understanding how enzymes work is essential if we are to understand life itself. In this project we will investigate the enzyme KARI by capturing a series of snapshots of its atomic structure as it progresses through its working cycle. In addition, we will make ....Snapshots of an enzyme in action: structural and mechanistic studies on the catalytic cycle of Escherichia coli ketol-acid reductoisomerase. Enzymes are required for almost every process that occurs in a living organism. For this reason, understanding how enzymes work is essential if we are to understand life itself. In this project we will investigate the enzyme KARI by capturing a series of snapshots of its atomic structure as it progresses through its working cycle. In addition, we will make a series of small alterations to the atomic structure that will allow us to understand how the individual parts work together.Read moreRead less
Structure and inhibition of acetohydroxyacid synthase. Acetohydroxyacid synthase (AHAS) has been identified as the target for several widely used herbicides known as the sulfonylureas and imidazolinones. World-wide, these two herbicides account for $US2 billion in annual sales. The aim is to determine the three-dimensional structure of AHAS from several sources and in complex with these herbicides. Furthermore, AHAS appears to be an excellent target for the development of antibacterial compounds ....Structure and inhibition of acetohydroxyacid synthase. Acetohydroxyacid synthase (AHAS) has been identified as the target for several widely used herbicides known as the sulfonylureas and imidazolinones. World-wide, these two herbicides account for $US2 billion in annual sales. The aim is to determine the three-dimensional structure of AHAS from several sources and in complex with these herbicides. Furthermore, AHAS appears to be an excellent target for the development of antibacterial compounds and fungicides. Knowledge of the three dimensional structures of these enzymes will be important in the rational design of more effective inhibitors with improved selectivity.Read moreRead less