The Effect Of Human ApoE Isoforms And ApoE Receptors On The Clearance Of Oligomeric A 42 By Hepatocytes In Vitro
Funder
National Health and Medical Research Council
Funding Amount
$424,801.00
Summary
Alzheimer's disease (AD) is a progressive memory disorder. Increased production of a short peptide called amyloid- (A ) aggregates to form the sticky masses in the brains of AD patients. The amount of A in the brain is a balance between production and clearance. Surprisingly, we recently demonstrated that the liver clears the majority of A . These results connect AD and cardiovascular disease (CVD), enabling current CVD therapeutics to target A clearance by the liver.
Proteome mapping of the model fungal plant pathogen Stagonospora nodorum using LC-LC-MS/MS. Stagonospora nodorum is a fungus that causes leaf and glume blotch disease on wheat. This disease alone causes $55 million dollars in yield losses per annum in Australia. This project aims to identify the proteins produced by Stagonospora nodorum through the development of a new proteomics technique. Two clear benefits to the community resulting from this project will emerge. The first will be the expert ....Proteome mapping of the model fungal plant pathogen Stagonospora nodorum using LC-LC-MS/MS. Stagonospora nodorum is a fungus that causes leaf and glume blotch disease on wheat. This disease alone causes $55 million dollars in yield losses per annum in Australia. This project aims to identify the proteins produced by Stagonospora nodorum through the development of a new proteomics technique. Two clear benefits to the community resulting from this project will emerge. The first will be the expert training of a student in proteomics, a skill that is keenly sought. Secondly, the identification of these pathogen proteins will lead to new strategies to better control the disease and secure the supply of wheat.Read moreRead less
A proteomic approach to identifying the signaling pathway(s) by which acute oxidative stress causes cell death by apoptosis. Oxidative stress following traumatic injury (heart attack or stroke) is known to activate signaling pathways leading to programmed cell death (apoptosis). The aim of this project is to develop methods to identify the signaling proteins involved. Identifying proteins involved in causing cell death will be useful in developing diagnostic tools as well as providing potential ....A proteomic approach to identifying the signaling pathway(s) by which acute oxidative stress causes cell death by apoptosis. Oxidative stress following traumatic injury (heart attack or stroke) is known to activate signaling pathways leading to programmed cell death (apoptosis). The aim of this project is to develop methods to identify the signaling proteins involved. Identifying proteins involved in causing cell death will be useful in developing diagnostic tools as well as providing potential therapeutic possibilities.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
Mammalian histidine kinase: its characterisation and role in hepatic cellular proliferation. Protein kinases regulate all aspects of cellular metabolism, but there is a class of protein kinase, histidine kinases, which exists in mammalian cells, about which remarkably little is understood. This project will be the first detailed characterisation of such an enzyme and investigation of its cellular function. The enzyme to be characterised is hepatic and it has been implicated in the regulation of ....Mammalian histidine kinase: its characterisation and role in hepatic cellular proliferation. Protein kinases regulate all aspects of cellular metabolism, but there is a class of protein kinase, histidine kinases, which exists in mammalian cells, about which remarkably little is understood. This project will be the first detailed characterisation of such an enzyme and investigation of its cellular function. The enzyme to be characterised is hepatic and it has been implicated in the regulation of DNA replication in regenerating liver. We shall obtain a detailed picture of the role of this histidine kinase in liver cell biology and an insight into the more general biological role of this class of enzyme.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560712
Funder
Australian Research Council
Funding Amount
$630,837.00
Summary
State-of-the-art biophysical tools for the characterisation of molecular interactions. In the current era of 'the genome' there is more demand than ever before for the characterisation of the gene products - the oligonucleotides and proteins that carry out the important functions in the cell. The current proposal is to acquire a suite of instrumentation to characterise the kinetics, thermodynamics and overall affinities of interactions between biological macromolecules and their physiological bi ....State-of-the-art biophysical tools for the characterisation of molecular interactions. In the current era of 'the genome' there is more demand than ever before for the characterisation of the gene products - the oligonucleotides and proteins that carry out the important functions in the cell. The current proposal is to acquire a suite of instrumentation to characterise the kinetics, thermodynamics and overall affinities of interactions between biological macromolecules and their physiological binding partners or with novel ligands. This will reveal the role of the macromolecules of interest in the cell, and potentially lead to the discovery of drug molecules which could interfere with molecular interactions underlying disease.Read moreRead less
Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug ta ....Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug targets. This research will lead to new strategies in the design of improved anticancer drugs, which is an important Australian research priority that will promote and maintain good health, and provide potential commercial outcomes.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100125
Funder
Australian Research Council
Funding Amount
$330,000.00
Summary
Oxidative stress bioanalytical facility. The primary national benefit of this application is that it will provide a currently unavailable, state-of-the-art facility for Australian scientists to define precisely how changes in cellular redox state contribute to biological processes relevant to health and diseases. The facility will uniquely complement, and in many cases integrate with existing facilities in this area of research in Australia. It will act as a platform for major national and inter ....Oxidative stress bioanalytical facility. The primary national benefit of this application is that it will provide a currently unavailable, state-of-the-art facility for Australian scientists to define precisely how changes in cellular redox state contribute to biological processes relevant to health and diseases. The facility will uniquely complement, and in many cases integrate with existing facilities in this area of research in Australia. It will act as a platform for major national and international research collaborations, develop cutting-edge technology and unique local skills, and contribute to Australia maintaining a leading position in redox-related research in biology and medicine. In doing so, the facility will increase the likelihood of gaining future, value-adding funding.Read moreRead less
Understanding The Acute And Cumulative Metabolic Effects Of Prolonged Sitting In Adults
Funder
National Health and Medical Research Council
Funding Amount
$416,597.00
Summary
Sedentary behaviour (sitting time) has been linked to an increased risk of chronic illnesses, including type 2 diabetes and obesity, but recent evidence suggests that light-intensity activity (non-exercise activities of daily living) is associated with reduced risk. These studies will examine whether breaking up sitting time with frequent short periods of activity can overcome the negative effects of prolonged sitting on blood glucose and blood fats in overweight older adults.
Molecular machines: regulation of the catalysis and rotation of the enzyme ATP synthase. This project aims to elucidate the regulation of the molecular machine ATP synthase. ATP synthase is an enzyme that performs a critical role in all cells - the synthesis of ATP, the universal biological energy currency. It is known that the enzyme operates via rotation of a central stalk which is driven by a hydrogen ion gradient across a membrane. Constructs of this molecule have been envisaged in the desig ....Molecular machines: regulation of the catalysis and rotation of the enzyme ATP synthase. This project aims to elucidate the regulation of the molecular machine ATP synthase. ATP synthase is an enzyme that performs a critical role in all cells - the synthesis of ATP, the universal biological energy currency. It is known that the enzyme operates via rotation of a central stalk which is driven by a hydrogen ion gradient across a membrane. Constructs of this molecule have been envisaged in the design of future biological nano-motors. Our work will provide an understanding of the regulation of this enzyme with potential application in the control of nano-motors.Read moreRead less