Understanding and exploiting bacterial sulfatases. Bacterial sulfatases participate in environmental nutrient cycling and are implicated in bacterial pathogenesis mechanisms. These enzymes catalyze the hydrolysis of sulfate esters and possess an unusual posttranslational active-site modification where a cysteine residue is oxidized to formylglycine. We will study the mechanism of these enzymes in detail and design inhibitors that exploit the reactivity of this aminoacid. This work has significan ....Understanding and exploiting bacterial sulfatases. Bacterial sulfatases participate in environmental nutrient cycling and are implicated in bacterial pathogenesis mechanisms. These enzymes catalyze the hydrolysis of sulfate esters and possess an unusual posttranslational active-site modification where a cysteine residue is oxidized to formylglycine. We will study the mechanism of these enzymes in detail and design inhibitors that exploit the reactivity of this aminoacid. This work has significance because of application to areas that include the treatment of cancer and bacterial infections. Additionally, we will clone novel carbohydrate sulfatases from the heparin-degrading bacterium Flavobacterium heparinum. These sulfatases will have use in biotechnology for characterization of sulfated glycoconjugates.Read moreRead less
Mass Spectrometric Investigations of Conformation and Dynamics of Biological Complexes. The new collaboration between the leading mass spectrometry groups at University Wollongong and Cambridge University will benefit both partners. Researchers at Wollongong will have access to an ion mobility mass spectrometry technology not currently available in Australia that will contribute to our understanding of complicated cellular processes such as chromosome replication. The researchers' experience wit ....Mass Spectrometric Investigations of Conformation and Dynamics of Biological Complexes. The new collaboration between the leading mass spectrometry groups at University Wollongong and Cambridge University will benefit both partners. Researchers at Wollongong will have access to an ion mobility mass spectrometry technology not currently available in Australia that will contribute to our understanding of complicated cellular processes such as chromosome replication. The researchers' experience with this technology will pave the way for introduction of the technology to Australia and benefit the wider scientific community in wide-ranging projects such as development of new antibiotics and vaccines. Students from both institutions will benefit from experiencing science from an international perspective.Read moreRead less
Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly whe ....Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly where they act in the brain. Read moreRead less
Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly whe ....Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly where they act in the brain. Read moreRead less
Development of Pyrrolopyrimidines as Inhibitors of ATP-Binding Proteins. This project seeks to generate analogues of natural products that have been found to be active against cancer cells and tropical parasites. The new materials produced by this project will aid in the study of biochemical processes involved in diseases such as cancer and lymphatic filariasis, thus leading the way to development of these compounds as potential treatments for such diseases.
Targeted isolation of specific marine bacterial species associated with higher organsims for the purpose of discovering new antimicrobial compounds. Specific bacterial species that are commonly found in association with marine plants and animals often produce active secondary metabolites. The aim of this project is to apply our understanding of these bacterial-host associations to the targeted isolation of novel antimicrobials from the marine environment. While these new compounds will undoubted ....Targeted isolation of specific marine bacterial species associated with higher organsims for the purpose of discovering new antimicrobial compounds. Specific bacterial species that are commonly found in association with marine plants and animals often produce active secondary metabolites. The aim of this project is to apply our understanding of these bacterial-host associations to the targeted isolation of novel antimicrobials from the marine environment. While these new compounds will undoubtedly have a number of commercial applications this project focuses on the development of products for dental hygiene in animals. Generally, the urgent need for new antimicrobial compounds to combat the growing number of microbes that are resistant to current antibiotics highlights the importance of this project.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882289
Funder
Australian Research Council
Funding Amount
$520,000.00
Summary
New generation mass spectrometers for characterisation of molecular shape and size. The ion mobility mass spectrometer (IMMS at UOW) will be the first of its kind in Australia, and together with the ion trap mass spectrometer (ITMS at ANU) will continue the tradition of this partnership in providing researchers with cutting-edge instrumentation for nationally and internationally important projects including: (i) fundamental understanding of the ways in which biomolecules recognize one another, ( ....New generation mass spectrometers for characterisation of molecular shape and size. The ion mobility mass spectrometer (IMMS at UOW) will be the first of its kind in Australia, and together with the ion trap mass spectrometer (ITMS at ANU) will continue the tradition of this partnership in providing researchers with cutting-edge instrumentation for nationally and internationally important projects including: (i) fundamental understanding of the ways in which biomolecules recognize one another, (ii) investigating the structure(s) of lipids (fats) in cardiovascular disease and cataract, (iii) developing anticancer drugs, and (iv) development of new materials.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668543
Funder
Australian Research Council
Funding Amount
$280,000.00
Summary
A high resolution, high-throughput chromatographic system for separation and characterisation of complex samples. Purchase of this equipment will support innovative and collaborative research addressing three of the National Research Priority areas. For example, defining novel drug delivery systems, or the chemical components present in Australia's bioresources, addresses 'Frontier technologies for building and transforming Australian industries', particularly the priority goals of breakthrough ....A high resolution, high-throughput chromatographic system for separation and characterisation of complex samples. Purchase of this equipment will support innovative and collaborative research addressing three of the National Research Priority areas. For example, defining novel drug delivery systems, or the chemical components present in Australia's bioresources, addresses 'Frontier technologies for building and transforming Australian industries', particularly the priority goals of breakthrough science and frontier technologies. The research into trace components in food products, and on fruit fly chemistry, relates to National Research priority four 'Safeguarding Australia', with a priority goal of protecting Australia from invasive diseases and pests. Nutraceutical research addresses the goal of 'Promoting and maintaining good health'.Read moreRead less
Total chemical synthesis of a redesigned enzyme, HIV-1 PR, containing an artificial tunable catalytic apparatus. The research project proposed represents a novel approach using total chemical synthesis to study the enzyme action of the HIV-1 PR, an aspartyl protease essential for the replication of AIDS virus. The redesign of the catalytic apparatus will allow us to investigate molecular aspects of its action. The synthetic polypeptide chain will be folded and characterised for the correct folde ....Total chemical synthesis of a redesigned enzyme, HIV-1 PR, containing an artificial tunable catalytic apparatus. The research project proposed represents a novel approach using total chemical synthesis to study the enzyme action of the HIV-1 PR, an aspartyl protease essential for the replication of AIDS virus. The redesign of the catalytic apparatus will allow us to investigate molecular aspects of its action. The synthetic polypeptide chain will be folded and characterised for the correct folded structure by NMR, and assayed for enzymatic activity. It can be expected that significant new insights into the molecular basis of the properties of the HIV-1 PR will be obtained. This will be an important contribution to biomedical research.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