Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668534
Funder
Australian Research Council
Funding Amount
$770,000.00
Summary
High resolution bioanalytical Fourier transform mass spectrometer combined with liquid chromatograph. This project extends a network of advanced technology for bioanalysis that enables discoveries in biotechnology, molecular medicine and biochemistry. The proposed equipment includes the most powerful mass spectrometer (MS) currently available for bioanalysis to complement an existing network of instruments at four universities in Sydney. These include 3 of 4 nodes of the Australian Proteome Anal ....High resolution bioanalytical Fourier transform mass spectrometer combined with liquid chromatograph. This project extends a network of advanced technology for bioanalysis that enables discoveries in biotechnology, molecular medicine and biochemistry. The proposed equipment includes the most powerful mass spectrometer (MS) currently available for bioanalysis to complement an existing network of instruments at four universities in Sydney. These include 3 of 4 nodes of the Australian Proteome Analysis Facility (APAF). The new technology is a missing link in bioanalytical capability where other instruments are not sufficiently sensitive. The instrument will be managed by MS specialists at the Bioanalytical Mass Spectrometry Facility at UNSW (www.bmsf.unsw.edu.au) where access by and training of users is well established.Read moreRead less
Characterization of erythroid differentiation related factor (EDRF): a novel a-globin binding protein. Hemoglobin, a four-subunit protein comprising two alpha and two beta polypeptide chains, is the essential oxygen transporter found in all mammals. Problems with the synthesis of hemoglobin can give rise to a range of common and serious human disorders, including thalassaemia and anemia. We have discovered a protein, EDRF, that appears to interact directly with alpha-globin (but not beta-globin) ....Characterization of erythroid differentiation related factor (EDRF): a novel a-globin binding protein. Hemoglobin, a four-subunit protein comprising two alpha and two beta polypeptide chains, is the essential oxygen transporter found in all mammals. Problems with the synthesis of hemoglobin can give rise to a range of common and serious human disorders, including thalassaemia and anemia. We have discovered a protein, EDRF, that appears to interact directly with alpha-globin (but not beta-globin) and to play a role in the regulation of hemoglobin production. We now seek to understand the nature of this interaction at a molecular level and mechanistic level.Read moreRead less
Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding ....Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding protein domains with the goal of selectively blocking these inappropriate interactions. Additionally, these engineered proteins have potential uses as biochemical tools such as to help delineate the functions of natural proteins with no known functions.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 basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Identification of novel biomarkers in tears for prostate cancer diagnosis and prognosis. The purpose of this study is to identify novel biomarkers in the tears of patients with CaP. The use of the several techniques will increase the chance of success and enable us to find more diagnostic markers. If successful, the identified proteins may be used to diagnose and determine the stage of cancer. This will help guide clinicians in choosing the best treatment methods for an individual patient. The m ....Identification of novel biomarkers in tears for prostate cancer diagnosis and prognosis. The purpose of this study is to identify novel biomarkers in the tears of patients with CaP. The use of the several techniques will increase the chance of success and enable us to find more diagnostic markers. If successful, the identified proteins may be used to diagnose and determine the stage of cancer. This will help guide clinicians in choosing the best treatment methods for an individual patient. The markers may also be used to monitor the disease progress and the effects of treatment. The results from this study may improve the prognosis of CaP patients.Read moreRead less
Identification of novel biomarkers for diabetic retinopathy in tears. There are around 134,000 people with diabetic retinopathy in Australia. The disease affects patients' physical and mental state and economical and social cost is enormous. This research aims to find new biomarkers for the disease which may lead to better treatment and management. Patient's quality of life may be significantly improved by early diagnosis and treatment and the burden to the community reduced. This project also g ....Identification of novel biomarkers for diabetic retinopathy in tears. There are around 134,000 people with diabetic retinopathy in Australia. The disease affects patients' physical and mental state and economical and social cost is enormous. This research aims to find new biomarkers for the disease which may lead to better treatment and management. Patient's quality of life may be significantly improved by early diagnosis and treatment and the burden to the community reduced. This project also gives industrial partners the opportunity to develop new products to diagnose and monitor the disease.Read moreRead less
Functional Dissection of the Bacterial Replisome. We now have the complete sequences of genes in humans and many other organisms, but we know much less about how the protein products of the genes communicate with each other to create and grow cells. Australia has recently invested heavily in state-of-the-art instruments that can be used to tackle these problems. This project will involve close interaction of four laboratories to use new instruments to determine how a large assembly of proteins i ....Functional Dissection of the Bacterial Replisome. We now have the complete sequences of genes in humans and many other organisms, but we know much less about how the protein products of the genes communicate with each other to create and grow cells. Australia has recently invested heavily in state-of-the-art instruments that can be used to tackle these problems. This project will involve close interaction of four laboratories to use new instruments to determine how a large assembly of proteins interact in a biological machine that makes DNA. This process occurs in similar ways in all organisms, and is essential for life. Understanding how DNA is made will help scientists to develop new antibacterial drugs, and learn how to make practical use of molecular machines that imitate biology.Read moreRead less
Mapping Protein Contacts and Conformational Changes in Macromolecular Assemblies. We now have a great deal of information about the structures of proteins that interact to do much of the chemistry that governs the lives of cells and organisms, but are just beginning to understand how proteins communicate with each other in the large, dynamic molecular machines that carry out many cellular functions. Australia has invested in expensive instrumentation that can be used in conjunction with new labo ....Mapping Protein Contacts and Conformational Changes in Macromolecular Assemblies. We now have a great deal of information about the structures of proteins that interact to do much of the chemistry that governs the lives of cells and organisms, but are just beginning to understand how proteins communicate with each other in the large, dynamic molecular machines that carry out many cellular functions. Australia has invested in expensive instrumentation that can be used in conjunction with new laboratory methods to develop better understanding of how these machines work, and how they malfunction in disease. This project will bring together four scientists with a unique combination of expertise and novel technologies to develop understanding of changes in structure of a large protein complex in different functional states.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