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Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
Special Research Initiatives - Grant ID: SR0354892
Funder
Australian Research Council
Funding Amount
$40,000.00
Summary
The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these ....The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these enzymes. However this initiative aims to network their efforts by value-adding to the current protease research through promoting national and international collaborations to improve our understanding of biology, and encourage exploitation of proteases/inhibitors/receptors for pharmaceutical and industrial applications.Read moreRead less
The development of a rapid diagnostic test for heparanase activity. Heparanase is an enzyme that has been implicated in a number of disease states such as cancer, arthritis, multiple sclerosis and other inflammatory diseases. Characterisation of this enzyme has been slow, due in part to the lack of a reliable direct activity assay. Using a multi-disciplinary approach, this project seeks to establish a rapid assay that will provide easy determination of heparanase activity. Furthermore, this a ....The development of a rapid diagnostic test for heparanase activity. Heparanase is an enzyme that has been implicated in a number of disease states such as cancer, arthritis, multiple sclerosis and other inflammatory diseases. Characterisation of this enzyme has been slow, due in part to the lack of a reliable direct activity assay. Using a multi-disciplinary approach, this project seeks to establish a rapid assay that will provide easy determination of heparanase activity. Furthermore, this assay could provide a useful diagnostic tool in a clinical environment that would allow for the rapid assessment of these diseases, their progression and indeed response to therapy.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
Proteomics of the Influenza Virus for In-field Surveillance. The influenza virus continues to pose a serious health risk to Australians and remains a leading cause of death. The molecular characterisation of emerging strains of the virus lies at the heart of current surveillance procedures vital to vaccine preparation and the development of new anti-viral drugs. This research will advance a world-first proteomics surveillance of the virus developed in this laboratory that will enable it to be ch ....Proteomics of the Influenza Virus for In-field Surveillance. The influenza virus continues to pose a serious health risk to Australians and remains a leading cause of death. The molecular characterisation of emerging strains of the virus lies at the heart of current surveillance procedures vital to vaccine preparation and the development of new anti-viral drugs. This research will advance a world-first proteomics surveillance of the virus developed in this laboratory that will enable it to be characterised in-field at the site(s) of infection outbreaks. This rapid response is vital, particularly in the event of a pandemic or a deliberate release of the virus in a bioterrorist attack.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560685
Funder
Australian Research Council
Funding Amount
$451,000.00
Summary
Scanning Probe Microscopy for Bioelectrochemistry. New methods to study the fundamental properties of biological samples, in particular proteins, are continuing to advance and impact on society. We will establish a leading edge facility for high-resolution imaging of biomolecules with redox functions. This will enable the continued development of new enzyme based diagnostic tests by understanding the dynamic nature of coupled electron and molecular interactions with redox enzymes in solution. Th ....Scanning Probe Microscopy for Bioelectrochemistry. New methods to study the fundamental properties of biological samples, in particular proteins, are continuing to advance and impact on society. We will establish a leading edge facility for high-resolution imaging of biomolecules with redox functions. This will enable the continued development of new enzyme based diagnostic tests by understanding the dynamic nature of coupled electron and molecular interactions with redox enzymes in solution. The bioelectrochemical imaging facility will be unique in Australia and establish an important cross-disciplinary approach within the international community.Read moreRead less
Chemical synthesis of cancer-associated glycoproteins. Glycosylation of proteins is an extremely common event which plays an important role in a variety of biological processes. Aberrant glycosylation and over-production of glycoproteins is associated with numerous cancer types (including breast, prostate, ovarian and small lung) and are recognised as promising agents for disease diagnosis and vaccine development. A range of cancer-associated glycoproteins will be synthesised in this research p ....Chemical synthesis of cancer-associated glycoproteins. Glycosylation of proteins is an extremely common event which plays an important role in a variety of biological processes. Aberrant glycosylation and over-production of glycoproteins is associated with numerous cancer types (including breast, prostate, ovarian and small lung) and are recognised as promising agents for disease diagnosis and vaccine development. A range of cancer-associated glycoproteins will be synthesised in this research program using a number of novel chemical technologies. These glycoproteins will be used to develop cancer vaccines and diagnostics. Cancer is a severe burden on the Australian community and on the economy, therefore this research will be of significant benefit to Australia.Read moreRead less
Development of therapeutic agents that target carbonic anhydrase enzymes. This research will discover new chemical entities (compounds) that may lead to therapies for the treatment of cancer, glaucoma and malaria. The research underpins a mechanism to add value to our compounds before partnering with industry to transform the discoveries made here to deliverable therapies that could benefit the health of millions, thus offering a potentially high value contribution to the Australian economy. The ....Development of therapeutic agents that target carbonic anhydrase enzymes. This research will discover new chemical entities (compounds) that may lead to therapies for the treatment of cancer, glaucoma and malaria. The research underpins a mechanism to add value to our compounds before partnering with industry to transform the discoveries made here to deliverable therapies that could benefit the health of millions, thus offering a potentially high value contribution to the Australian economy. The experience and commitment of the multi-disciplinary network of researchers offers exceptional training and employment opportunities for tomorrow's scientists in techniques for discovery and characterisation of novel chemicals, and their interaction with disease targets.Read moreRead less
Investigations into the Versatility of Peptide Nucleic Acid Conjugates. Neurodegeneration and cancer are two of the greatest frontiers in modern medicine. They impose significant medical, financial and social burdens on sufferers, carers and the wider community. Novel technologies with the ability to help diagnosis, enlighten researchers to the biological principles governing the disease and that can make a contribution to prevention, quality of life issues and survival of sufferers are of utmos ....Investigations into the Versatility of Peptide Nucleic Acid Conjugates. Neurodegeneration and cancer are two of the greatest frontiers in modern medicine. They impose significant medical, financial and social burdens on sufferers, carers and the wider community. Novel technologies with the ability to help diagnosis, enlighten researchers to the biological principles governing the disease and that can make a contribution to prevention, quality of life issues and survival of sufferers are of utmost importance. This project aims to make a significant contribution to these areas using antisense technologies against some previously studied targets.Read moreRead less
Functionalised MMP Inhibitors as Radiodiagnostic, Radiotherapeutic, and Radiation-Sensitising Agents for Metastatic Cancer. Identifying and treating malignant cancers is one of the major challenges facing the scientific and medical communities. In order to minimise side effects that accompany most treatments of cancer it is necessary to find ways of targeting the therapy to tumours and away from healthy organs. A difference between tumours and healthy tissues is the amount of the proteins (calle ....Functionalised MMP Inhibitors as Radiodiagnostic, Radiotherapeutic, and Radiation-Sensitising Agents for Metastatic Cancer. Identifying and treating malignant cancers is one of the major challenges facing the scientific and medical communities. In order to minimise side effects that accompany most treatments of cancer it is necessary to find ways of targeting the therapy to tumours and away from healthy organs. A difference between tumours and healthy tissues is the amount of the proteins (called MMPs) that tumours use to break out of their surroundings, to break into and out of the blood system, and to establish new colonies of cancer cells or metastases. This difference also distinguishes the most aggressive cancers. The purpose of this project is to develop means of identifying and targeting cancers using molecules that bind to these MMP proteins.Read moreRead less