The Nutritional Geometry Of Ageing In A Rodent Model
Funder
National Health and Medical Research Council
Funding Amount
$979,269.00
Summary
A central belief in ageing research is that eating fewer calories prolongs life, and that the source of calories (carbohydrate, fat or protein) is irrelevant. However, a critical assessment indicates that this conclusion is premature. We will use recent techniques in nutrition to define for the first time in mammals the relationship between diet and ageing in a normal and a prematurely ageing strain of mice. The project will provide a novel nutritional approach for promoting healthy ageing.
Mechanisms Of Proteolysis Of Proteins Containing Oxidised Amino Acids
Funder
National Health and Medical Research Council
Funding Amount
$406,320.00
Summary
There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related d ....There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related diseases, such as Alzheimer s disease and other neurological disorders, are also claimed to be associated with deranged protein oxidation, and accumulation of oxidised products. There is clear evidence that certain defensive mechanisms, such as those acting to remove invading organisms and clear wounds, are also associated with an enhanced production of oxidised proteins. Perhaps the most important component of defense against oxidised proteins is their removal by complete breakdown to constituent components, and excretion. Normally, the machinery for breakdown of proteins is in vast excess over the required rate of degradation. However, clearly in these conditions of accumulation of oxidised proteins, this is no longer the case, or no longer suffices. Mechanisms by which oxidised proteins are degraded are poorly understood, and quite controversial. Therefore, the present studies bring to bear a new approach to studying this issue, which has been developed by the applicants. The aim is to reveal mechanisms involved in the breakdown of proteins containing oxidised amino acids, both in cellular systems, and in vivo. Such an understanding may allow us to envisage how to remove oxidised proteins by therapeutic means and therefore interfere with the development of age-related diseases such as Alzheimer s disease and cataract formation and the diseases of the blood vessels associated with attack and stroke.Read moreRead less
A Cognitive And Neuroimaging Study Of Exceptionally Old Individuals: Sydney Centenarian Study
Funder
National Health and Medical Research Council
Funding Amount
$857,197.00
Summary
Australia has an ageing society. Individuals over the age of 95 years are the fastest growing proportion of this population. Many of these individuals retain good cognitive function. The Sydney Centenarian Study will recruit all individuals 95 and over in 7 local government areas in Sydney to assess their brain function to determine which cognitive faculties are more or less affected, and how this relates to changes on brain scans. This will be related to neuropathology.
Immunisation In Under Studied And Special Risk Populations: Closing The Gap In Knowledge Through A Multidisciplinary Approach
Funder
National Health and Medical Research Council
Funding Amount
$2,499,969.00
Summary
Much of the vaccine research which informs national policy is conducted by the pharmaceutical industry or by government. However, there are critical research gaps in special-risk and under-served populations where targeted research is not commercially viable. These include research in the extremes of age, Indigenous Australians, migrants, refugees, immunosuppressed and traveller populations. This CRE will address research gaps in such populations, which have not been addressed elsewhere, using n ....Much of the vaccine research which informs national policy is conducted by the pharmaceutical industry or by government. However, there are critical research gaps in special-risk and under-served populations where targeted research is not commercially viable. These include research in the extremes of age, Indigenous Australians, migrants, refugees, immunosuppressed and traveller populations. This CRE will address research gaps in such populations, which have not been addressed elsewhere, using novel, multidisciplinary methods.Read moreRead less
Therapeutic Implications Of A Molecular Link Between Survivin And Telomerase Reverse Transcriptase
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
A unifying feature of all types of cancer cells is that they are immortal. Our investigations will build upon our recent results that showed the gene survivin is involved in cancer cell immortalisation. We will characterise a molecular link between survivin and the enzyme telomerase, which is central to cancer cell immortality. Furthermore, we will demonstrate the therapeutic potential of turning off both survivin and telomerase as a novel approach to halting the growth of cancer cells.
Through this Australia Fellowship, Prof Keall and his tream will substantially improve the accuracy and effectiveness of radiation therapy for cancer by developing new techniques that will be able to ‘target’ a tumour in real-time and ‘concentrate fire’ on the most resistant and aggressive parts of it. Success in physiological targeting will create a paradigm shift in radiation therapy and could literally be a lifesaver. It’s a big challenge, but if this five-year research program succeeds, it w ....Through this Australia Fellowship, Prof Keall and his tream will substantially improve the accuracy and effectiveness of radiation therapy for cancer by developing new techniques that will be able to ‘target’ a tumour in real-time and ‘concentrate fire’ on the most resistant and aggressive parts of it. Success in physiological targeting will create a paradigm shift in radiation therapy and could literally be a lifesaver. It’s a big challenge, but if this five-year research program succeeds, it will pay big dividendsRead moreRead less
Benthic Processes and Oceanic Internal Waves. Direct observations will be made of the turbulent motion and sediment re-suspension near the sea bed of the ocean in regions strongly influenced by tides and internal waves. Combined with numerical models, the study will provide new insights into processes that are of fundamental importance to understanding the global dissipation of tidal energy and the role of internal waves in these processes. With observations from the continental slope region of ....Benthic Processes and Oceanic Internal Waves. Direct observations will be made of the turbulent motion and sediment re-suspension near the sea bed of the ocean in regions strongly influenced by tides and internal waves. Combined with numerical models, the study will provide new insights into processes that are of fundamental importance to understanding the global dissipation of tidal energy and the role of internal waves in these processes. With observations from the continental slope region of the Australian North West Shelf, results will also benefit the offshore engineering industry through knowledge of sediment scour and loadings on offshore structures.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100029
Funder
Australian Research Council
Funding Amount
$700,000.00
Summary
High Resolution PET-CT for Small Animal Molecular and Anatomical Imaging. This project will integrate a next generation small animal PET-CT instrument into the Sydney Imaging multi-modality imaging ecosystem. PET-CT enables the investigation of molecular function and anatomical structure in complex living organisms. This platform will enable research as diverse as the development and in-vivo characterisation of new chemical probes and nanoparticles that bind to specific protein targets in the bo ....High Resolution PET-CT for Small Animal Molecular and Anatomical Imaging. This project will integrate a next generation small animal PET-CT instrument into the Sydney Imaging multi-modality imaging ecosystem. PET-CT enables the investigation of molecular function and anatomical structure in complex living organisms. This platform will enable research as diverse as the development and in-vivo characterisation of new chemical probes and nanoparticles that bind to specific protein targets in the body, investigating mechanisms of brain plasticity in predictive learning, understanding the molecular pathways involved in neurodegeneration and cancer, developing novel methods for multi-modal image analysis, and developing and validating new radiation detectors for the next generation of imaging technology.Read moreRead less
Structure and function of a new class of multi-zinc finger (MZF) transcriptional regulators. An understanding of how genes are switched on and off during the development and lifetime of an organism is central to developing the ability to fight many diseases in a rational way. This project will advance our knowledge in this area at a fundamental molecular level by examining the mechanisms through which a specific set of proteins controls gene expression.
Physiology of tau protein: a novel role in scaffolding and intracellular distribution. Understanding brain function remains a challenge. This project will study the normal role of the Alzheimer's disease-related protein tau in brain function during ageing. This will significantly enhance current understanding of brain function.