Forging A New Understanding Of Iron In Neurodegenerative Disease.
Funder
National Health and Medical Research Council
Funding Amount
$598,573.00
Summary
Using the versatile model system, C. elegans, this proposal will define how normal functions of the brain become corrupted with age and hijacked by neurodegenerative diseases to cause dementia. Coupling specialised X-ray imaging only available at the Australian Synchrotron with the research excellence of the University of Melbourne, this Fellowship will provide a better understanding of normal ageing and how this relates to the development and progression of neurodegenerative diseases.
Identifying The Targets Of Myeloperoxidase-derived Oxidants In Plasma And Cells
Funder
National Health and Medical Research Council
Funding Amount
$237,258.00
Summary
Myeloperoxidase (MPO) is a haem enzyme, released by activated white blood cells, that catalyses the production of highly damaging chlorinated oxidants. These oxidants are known to play a major role in the human immune system by killing bacteria and other invading pathogens. However, excessive or misplaced generation of these oxidants results in tissue damage. This damage has been implicated in development of disease. For example, there is strong evidence for the involvement of MPO, and the oxida ....Myeloperoxidase (MPO) is a haem enzyme, released by activated white blood cells, that catalyses the production of highly damaging chlorinated oxidants. These oxidants are known to play a major role in the human immune system by killing bacteria and other invading pathogens. However, excessive or misplaced generation of these oxidants results in tissue damage. This damage has been implicated in development of disease. For example, there is strong evidence for the involvement of MPO, and the oxidants that it produces, in atherosclerosis. This disease is responsible for the death of around 40 % of the Australian population. There is no doubt that the oxidants produced by MPO cause major damage to tissues and extensive cell death. However, the mechanisms involved in this process remain to be established, due to a lack of sensitive and specific techniques for examining oxidant-mediated damage to individual target molecules. This study will identify the key targets of MPO-derived oxidants in plasma and cells using novel labelling techniques. This will provide valuable information about the mechanisms of oxidative damage and cytotoxicity. This will be important in the design of potential therapeutic agents to modulate and prevent the progression of degenerative diseases, such as atherosclerosis, that are linked with MPO.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
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882913
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Mass spectrometry facility for the quantitation and analysis of post-translationally modified peptides. This proposal will address a gap in our mass spectrometry capabilities and aid in our understanding of the cellular immune response and investigate the chemical diversity of the targets of immunity. This proposal has broad implications in the basic immunology of antigen presentation, in biomarker discovery as well as in the design of new vaccines in infectious disease and cancer and the develo ....Mass spectrometry facility for the quantitation and analysis of post-translationally modified peptides. This proposal will address a gap in our mass spectrometry capabilities and aid in our understanding of the cellular immune response and investigate the chemical diversity of the targets of immunity. This proposal has broad implications in the basic immunology of antigen presentation, in biomarker discovery as well as in the design of new vaccines in infectious disease and cancer and the development of therapies for autoimmune diseases. In addition to these key scientific outcomes this project will also facilitate the training of several new personnel in a skill area for which there is a critical shortage (mass spectrometry) and promote cross-disciplinary skills (immunology, biochemistry, proteomics).Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150101863
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Strained alkenes as chemical probes for cysteine sulfenic acid. This project aims to introduce strained alkenes as probes for cysteine sulfenic acid, a poorly understood biomarker for oxidative stress. This probe will enable rapid detection of cysteine sulfenic acid and meet an urgent need for tools to map cysteine redox signalling. Moreover, since many enzymes feature a cysteine sulfenic acid at their active site, the strained alkene probes will also serve as useful inhibitor probes of these en ....Strained alkenes as chemical probes for cysteine sulfenic acid. This project aims to introduce strained alkenes as probes for cysteine sulfenic acid, a poorly understood biomarker for oxidative stress. This probe will enable rapid detection of cysteine sulfenic acid and meet an urgent need for tools to map cysteine redox signalling. Moreover, since many enzymes feature a cysteine sulfenic acid at their active site, the strained alkene probes will also serve as useful inhibitor probes of these enzymes. Such inhibitor probes will provide critical information for potential therapeutic applications in human conditions associated with oxidative stress such as ageing, cancer, and heart disease.Read moreRead less
Understanding The Role And Mechanism Of Interaction Of Small Heat-shock Proteins In Age-related Disease
Funder
National Health and Medical Research Council
Funding Amount
$270,827.00
Summary
Protein precipitation is associated with a diversity of age-related diseases such as cataract and Alzheimer's. Within cells, a group of chaperones called the small heat-shock proteins (sHSPs) function by binding to destabilized proteins, however, common in vivo modifications can disrupt their cellular role leading to co-aggregation in a number of age-related diseases. This study will use state of the art mass spectrometry to examine the mechanism by which sHSPs interact with client proteins.
High-throughput microfluidic approach to mapping hierarchies of interactions in the gene regulation machinery. The exploration of protein-protein interactions networks is becoming an extremely active area of research in life sciences. The current project will develop new approaches to accelerate the discovery of novel interacting proteins participating in gene regulation, in order to understand how cells differentiate into different tissues and organs.