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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561041
Funder
Australian Research Council
Funding Amount
$347,358.00
Summary
A New Generation Biosensor and Fluorescence Facility for Proteomics. The complete DNA sequence (the genome) is now known for many organisms and advances are being made to identify the complement of messenger RNA (the transcriptome) and the resultant collection of proteins (the proteome). The genome is largely fixed while the transcriptome and proteome differ between cell types in an organism and constantly vary to adapt the cell to changing conditions. The mediators of these variations are prote ....A New Generation Biosensor and Fluorescence Facility for Proteomics. The complete DNA sequence (the genome) is now known for many organisms and advances are being made to identify the complement of messenger RNA (the transcriptome) and the resultant collection of proteins (the proteome). The genome is largely fixed while the transcriptome and proteome differ between cell types in an organism and constantly vary to adapt the cell to changing conditions. The mediators of these variations are proteins, interacting with each other and with signal molecules. The next frontier in molecular biology is to identify and quantify these protein interactions. Our two institutions have a very large cohort of biologists whose research on proteins would be greatly facilitated by the Biacore 3000 and the ISS K2.Read moreRead less
Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several labora ....Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several laboratories in Australia and overseas to develop new understanding of how the molecular machine that copies DNA works. This k nowledge could lead to new drugs, and will give us new information about how cellular machines function.Read moreRead less
Fragment Based Screening for new Antibiotics by Protein X-Ray Crystallography. Due in part to rising levels of antibiotic resistance, the death toll from pathogenic bacteria is expected to skyrocket over the next 15 years. There is therefore a pressing need for new antibiotics to treat bacterial infection. This project will use a relatively new discovery tool called fragment based screening to discover a new generation of antibacterial agents. This tool will allow for the rapid economical discov ....Fragment Based Screening for new Antibiotics by Protein X-Ray Crystallography. Due in part to rising levels of antibiotic resistance, the death toll from pathogenic bacteria is expected to skyrocket over the next 15 years. There is therefore a pressing need for new antibiotics to treat bacterial infection. This project will use a relatively new discovery tool called fragment based screening to discover a new generation of antibacterial agents. This tool will allow for the rapid economical discovery of new drugs, and will complement other investments in Australian biotechnology infrastructure.Read moreRead less
Macrocyclic Peptidomimetics. Proteins and peptides are among the most exquisite examples of hosts/guests for molecular recognition. Composed of amino acid building blocks, peptides are highly flexible and structurally promiscuous, switching between multiple structures (random/strand/sheet/turn/helical) in solution. Peptides pay a significant entropy penalty to organize into the one structure recognised by a biological receptor and responsible for activity. We are developing new macrocycles, comp ....Macrocyclic Peptidomimetics. Proteins and peptides are among the most exquisite examples of hosts/guests for molecular recognition. Composed of amino acid building blocks, peptides are highly flexible and structurally promiscuous, switching between multiple structures (random/strand/sheet/turn/helical) in solution. Peptides pay a significant entropy penalty to organize into the one structure recognised by a biological receptor and responsible for activity. We are developing new macrocycles, composed of molecular constraints and amino acids, organized into specific strand, turn, or helical shapes. These building blocks are more structured, more chemically stable, and have higher receptor affinities than peptides enabling potential uses as new biological tools, drug leads, catalysts, devices or new materials.Read moreRead less
Modulation of cellular metabolism by protein and peptide peroxides. Oxidation of peptides and proteins by a wide range of reactive radicals and other oxidants, in the presence of oxygen, generates protein peroxides. These species are now recognised to be key intermediates in both the deterioration of foods (e.g. development of rancidity and off-flavours, changes in colour and texture) and a number of human diseases, including cancer, heart disease and ageing. How these peroxides cause biological ....Modulation of cellular metabolism by protein and peptide peroxides. Oxidation of peptides and proteins by a wide range of reactive radicals and other oxidants, in the presence of oxygen, generates protein peroxides. These species are now recognised to be key intermediates in both the deterioration of foods (e.g. development of rancidity and off-flavours, changes in colour and texture) and a number of human diseases, including cancer, heart disease and ageing. How these peroxides cause biological perturbations is poorly understood. The proposed studies will provide valuable information as to how these peroxides affect cellular metabolism and provide key leads as to strategies which may prevent such damage.Read moreRead less
Mechanistic studies on the oxidation of amino acids, peptides and proteins and its biological consequences. Exposure of amino acids and proteins to radicals, oxidants, UV light, and metal ions results in oxidation, with consequent alteration to protein structure and function. It has been shown that these reactions occur during food spoilage, exposure of plants to excess UV light, and in a number of human diseases (e.g. heart disease and cancer). Despite evidence for a key role for protein oxidat ....Mechanistic studies on the oxidation of amino acids, peptides and proteins and its biological consequences. Exposure of amino acids and proteins to radicals, oxidants, UV light, and metal ions results in oxidation, with consequent alteration to protein structure and function. It has been shown that these reactions occur during food spoilage, exposure of plants to excess UV light, and in a number of human diseases (e.g. heart disease and cancer). Despite evidence for a key role for protein oxidation in these events, the fundamental chemistry and biochemistry of protein oxidation is incompletely understood. This is addressed in this project. Knowledge of the mechanisms of these reactions is a vital pre-requisite to the rational design of preventative strategies that might enhance food quality, minimise UV damage and enhance human health.Read moreRead less
The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform ....The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform for new biotech companies to be formed in Australia.Read moreRead less
The molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemis ....The molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemistry and spectroscopy will be used. This will be the first time that the enzymes of bacterial Mn2+-oxidation will have been characterised in such detail and will lead to a greater understanding of the process of bacterial manganese oxidation.Read moreRead less
Understanding and Inhibiting the P450 CYP24 enzyme, a target for cancer chemotherapeutics. This project falls within the National Research Priority of Promoting and Maintaining Good Health in the category of ageing well and productively. CYP24 inhibition provides a particular target for breast and prostate cancer which are the second leading cause of death in women and men, respectively. The proposed research will result in the production of CYP24 inhibitors that will be assessed in vivo at th ....Understanding and Inhibiting the P450 CYP24 enzyme, a target for cancer chemotherapeutics. This project falls within the National Research Priority of Promoting and Maintaining Good Health in the category of ageing well and productively. CYP24 inhibition provides a particular target for breast and prostate cancer which are the second leading cause of death in women and men, respectively. The proposed research will result in the production of CYP24 inhibitors that will be assessed in vivo at the Hanson Institute in Adelaide as potential anti-cancer drugs. Finally, there is a significant benefit in technology transfer to Australia from our collaborators in the USA in the field of computer aided inhibitor design.Read moreRead less