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
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
Gas Phase Dynamics of a Biological Molecular Machine: Fundamentals, Stoichiometries and Stabilities. Over the last twenty years advanced molecular measurement techniques have enabled the characterization of individual biological molecules (proteins and DNA) within different types of cells and diseased tissues. This project uses a new technique that literally "weighs" groups of proteins and/or DNA to help us understand how such large molecules fit together and function within cells (sometimes ref ....Gas Phase Dynamics of a Biological Molecular Machine: Fundamentals, Stoichiometries and Stabilities. Over the last twenty years advanced molecular measurement techniques have enabled the characterization of individual biological molecules (proteins and DNA) within different types of cells and diseased tissues. This project uses a new technique that literally "weighs" groups of proteins and/or DNA to help us understand how such large molecules fit together and function within cells (sometimes referred to as molecular machinery). More detailed knowledge of processes such as those involved in copying DNA when new cells are produced will, in the long term, improve our understanding and treatment of conditions or diseases that result from errors in molecular machinery. Read moreRead less
Carbohydrate language changes in vertebrate-pathogen co-evolution. This project aims to understand protein glycosylation’s role in host-pathogen relationships and cross-species transmission. Species specific sugars extensively modify cell surface and body fluid proteins. These glycans build a universal language that cells use and pathogens abuse. This project will use glycomics and glycoproteomics to uncover how pathogens learned to speak and interpret glyco-languages between different species. ....Carbohydrate language changes in vertebrate-pathogen co-evolution. This project aims to understand protein glycosylation’s role in host-pathogen relationships and cross-species transmission. Species specific sugars extensively modify cell surface and body fluid proteins. These glycans build a universal language that cells use and pathogens abuse. This project will use glycomics and glycoproteomics to uncover how pathogens learned to speak and interpret glyco-languages between different species. This project is expected to develop a glycan dictionary which could reveal host-pathogen co-evolution and glycosylation evolution in the Chordata phylum and counteract zoonoses threats.Read moreRead less
Rejuvenating adult stem cells. This project aims to uncover intimate links between metabolic regulation and longevity in adult stem cells, the source of all cells in the body. Understanding why we age and whether ageing is preventable are research challenges which must be first attacked at a cellular level. This project will try to rejuvenate aged stem cells by interfering with a prospective molecular master switch of aging and also develop an approach to identify and select youthful stem cells. ....Rejuvenating adult stem cells. This project aims to uncover intimate links between metabolic regulation and longevity in adult stem cells, the source of all cells in the body. Understanding why we age and whether ageing is preventable are research challenges which must be first attacked at a cellular level. This project will try to rejuvenate aged stem cells by interfering with a prospective molecular master switch of aging and also develop an approach to identify and select youthful stem cells. The results are expected to be important beyond informing the science of ageing, in the areas of tissue engineering, wound healing, embryology and cancer.Read moreRead less
Cellular Gene Regulation Networks. The benefit to Australia will be scientific in terms of providing an understanding of how cells integrate transcriptional control systems and the networks that are involved. This will inform research on folate deficiency and aberrant human development and towards identifying genes that are important in improving efficiency of microbial fermentations. Additional and more practical major benefits will follow from the development of tools to analyse interaction ....Cellular Gene Regulation Networks. The benefit to Australia will be scientific in terms of providing an understanding of how cells integrate transcriptional control systems and the networks that are involved. This will inform research on folate deficiency and aberrant human development and towards identifying genes that are important in improving efficiency of microbial fermentations. Additional and more practical major benefits will follow from the development of tools to analyse interactions between control systems, including software of value to the research community. The work will provide postgraduate students with major training in up-to-date genomic technologies, and in the interface between application of bioinformatics and experimental science.
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Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation r ....Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in weakening the structure of lesions and making them prone to rupture. Little is known about the fundamental chemistry of such damage; this will be addressed in the proposed program. The data obtained will underpin the development of new preventative and protective strategies to minimise lesion rupture and deaths from this major disease.Read moreRead less
All-in-vitro engineering and single molecule analysis of protein complexes. The production and engineering of proteins are key methodologies in life sciences. The current project aims to develop new approaches to accelerate the production and analysis of proteins and to apply them to increase our understanding of the basic mechanisms of cell self-maintenance.
Mechanisms and consequences of myeloperoxidase-mediated damage to glycosaminoglycans, proteins and proteoglycans. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in we ....Mechanisms and consequences of myeloperoxidase-mediated damage to glycosaminoglycans, proteins and proteoglycans. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in weakening the structure of lesions and making them prone to rupture. Little is known about the fundamental chemistry of such damage; this will be addressed in the proposed program. The data obtained will underpin the development of new preventative and protective strategies to minimise lesion rupture and deaths from this major disease.Read moreRead less