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
Regulation and function of a novel protein tyrosine phosphatase. A cell's ability to respond to its extracellular environment involves a complex and highly organised series of events referred to as cellular signalling. These signalling processes regulate fundamental cellular processes that underlie the growth and development of all living organisms. This proposal focuses on a group of enzymes known as the protein tyrosine phosphatases and their ability to regulate tyrosine phosphorylation-depe ....Regulation and function of a novel protein tyrosine phosphatase. A cell's ability to respond to its extracellular environment involves a complex and highly organised series of events referred to as cellular signalling. These signalling processes regulate fundamental cellular processes that underlie the growth and development of all living organisms. This proposal focuses on a group of enzymes known as the protein tyrosine phosphatases and their ability to regulate tyrosine phosphorylation-dependent signalling. We have identified a novel human protein tyrosine phosphatase and we aim to characterise its regulation and biological function.Read moreRead less
Characterisation of a novel protein tyrosine phosphatase. A cells ability to respond to its extracellular environment involves a complex and highly organised series of events referred to as cellular signalling. These signalling processes regulate fundamental cellular events that underlie the growth and development of all living organisms. This proposal focuses on a group of enzymes known as the protein tyrosine phosphatases and their ability to regulate tyrosine phosphorylation-dependent signa ....Characterisation of a novel protein tyrosine phosphatase. A cells ability to respond to its extracellular environment involves a complex and highly organised series of events referred to as cellular signalling. These signalling processes regulate fundamental cellular events that underlie the growth and development of all living organisms. This proposal focuses on a group of enzymes known as the protein tyrosine phosphatases and their ability to regulate tyrosine phosphorylation-dependent signalling. We have identified a novel human protein tyrosine phosphatase and we aim to characterise its function and the mechanism by which it is regulated.Read moreRead less
Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in bi ....Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in biotechnology. The ultimate aim is to create novel technologies for protein production, modification and analysis that will accelerate the pace of discovery in protein research, basic cell and organism biology, diagnostics, biotechnology and drug discovery. Read moreRead less
Structural studies on carbohydrate modifying enzymes. Carbohydrates form one of four major classes of biological macromolecules, and are major targets for drug design. We have developed methods for the production of carbohydrate synthesising enzymes and will determine the structures of these enzymes to provide the foundation for structure based design of inhibitors. The research will allow us to understand how these enzymes function in normal circumstances and how they malfunction in disease sta ....Structural studies on carbohydrate modifying enzymes. Carbohydrates form one of four major classes of biological macromolecules, and are major targets for drug design. We have developed methods for the production of carbohydrate synthesising enzymes and will determine the structures of these enzymes to provide the foundation for structure based design of inhibitors. The research will allow us to understand how these enzymes function in normal circumstances and how they malfunction in disease states such as cancer. The long-term outcome will be a significantly enhanced body of knowledge of this poorly understood group of enzymes and the development of new carbohydrate based chemicals with novel therapeutic applications.Read moreRead less
Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the ....Identification of functionally important autophosphorylation site(s) on ataxia telangiectasia and Rad 3 - related (ATR) protein kinase. The integrity of our genetic material must be maintained so that it can be passed on from one generation to the next and also to minimize the risk of cancer and other pathologies in an individual. There are multiple proteins involved in protecting our DNA including several enzymes that detect and signal DNA damage to a series of pathways involved in halting the passage of cells through the cell cycle so that repair can occur. This project studies the mechanism of action of one of these enzymes which will be of benefit in designing new compounds to fight disease. Read moreRead less
Unveiling and characterisation of a fundamental pathway important in cell division. This work will have a major impact by producing top quality research that addresses a fundamental biological question of relevance to all organisms. The research will advance understanding of genetic factors important in foetal and early childhood development and proliferative disorders that occur during ageing. This work will provide intellectual and practical training to Honours and PhD students and postdoctora ....Unveiling and characterisation of a fundamental pathway important in cell division. This work will have a major impact by producing top quality research that addresses a fundamental biological question of relevance to all organisms. The research will advance understanding of genetic factors important in foetal and early childhood development and proliferative disorders that occur during ageing. This work will provide intellectual and practical training to Honours and PhD students and postdoctoral researchers in the disciplines of Molecular Genetics, Molecular & Cellular Biology, Developmental Cell Biology, Mass Spectrometry and Proteomics, which will be of immense benefit to their scientific careers and the Australian scientific community.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
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