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Gene-environment Interaction In Healthy Brain Ageing And Age Related Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$2,162,805.00
Summary
Healthy ageing is characterised by low level of disability, high cognitive and functional capacity, and an active engagement in life. The most important ingredient of healthy ageing is a healthy brain, bereft of age-related diseases and dysfunction. Brain ageing and brain diseases are determined by multiple genetic factors that interact with environmental influences. The genes are multiple, the majority of which have a small influence. This study is an attempt to identify some of these genes and ....Healthy ageing is characterised by low level of disability, high cognitive and functional capacity, and an active engagement in life. The most important ingredient of healthy ageing is a healthy brain, bereft of age-related diseases and dysfunction. Brain ageing and brain diseases are determined by multiple genetic factors that interact with environmental influences. The genes are multiple, the majority of which have a small influence. This study is an attempt to identify some of these genes and investigate their interactions with environmental factors. It will use a unique resource, the NHMRC Australian Twin Registry (ATR) to identify elderly twins, and will also include the siblings of these twins so as to increase the ability to identify the important factors. The participants, who are listed on the ATR and recruited from NSW, Queensland and Victoria, will receive detailed neurological, psychiatric and cognitive assessments, and will undergo brain MRI scans. Their blood samples will be used to measure key chemicals that may affect brain ageing and to extract DNA for genetic tests. They will be followed-up every two years thereafter, and changes in their brain structure and cognitive functioning will be examined. Available statistical models will be used to examine gene-environment interactions and specific genes will be explored for their contribution to the additive genetic effects. This study will yield an important resource for national and international collaborations and has the potential to discover new genes.Read moreRead less
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
Mechanism Of Action Of Sec1p-like Proteins In Membrane Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$234,936.00
Summary
One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has ....One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has developed a complex assembly line of modifications that are added to proteins in a specific order as they travel to their final destination within the cell. This necessitates the accurate passage of molecules between compartments, a process known as vesicle transport. To orchestrate the complex network of vesicular transport steps between all of the various intracellular compartments it is necessary to employ complex machinery to guide and check that these steps occur with high fidelity. The goal of our research proposal is to define the function of one of the molecules involved in this control process, the so-called Sec1p proteins. The strength of our proposal lies in the diversity of our approach. We intend to explore the molecular advantages of a relatively simple eukaryotic organism, a yeast cell, and apply the findings obtained from this cell to a more complex but highly related vesicular transport process; that of the insulin-regulated movement of a glucose transporter in mammalian fat and muscle cells. While we intend to apply our findings to the treatment of patients with diabetes, it is our ultimate goal to be able to learn more about this fundamental cell biological process so that we can apply our knowledge to understanding many different disease states.Read moreRead less
Mechanism Of Action Of Sec1p-like Proteins In Membrane Trafficking.
Funder
National Health and Medical Research Council
Funding Amount
$440,250.00
Summary
One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has ....One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has developed a complex assembly line of modifications that are added to proteins in a specific order as they travel to their final destination within the cell. This necessitates the accurate passage of molecules between compartments, a process known as vesicle transport. To orchestrate the complex network of vesicular transport steps between all of the various intracellular compartments it is necessary to employ complex machinery to guide and check that these steps occur with high fidelity. The goal of our research proposal is to define the function of one of the molecules involved in this control process, the so-called Sec1p proteins. The strength of our proposal lies in the diversity of our approach. We intend to explore the molecular advantages of a relatively simple eukaryotic organism, a yeast cell, and apply the findings obtained from this cell to a more complex but highly related vesicular transport process; that of the insulin-regulated movement of a glucose transporter in mammalian fat and muscle cells. While we intend to apply our findings to the treatment of patients with diabetes, it is our ultimate goal to be able to learn more about this fundamental cell biological process so that we can apply our knowledge to understanding many different disease states.Read moreRead less
Making better decisions about built assets: learning by doing. This research will assist the built environment professions and their clients to make better decisions about new developments through a novel 'learning by doing' approach. Used successfully in other fields such as natural resource management, this idea will capitalise on the large number of asset investments undertaken to benchmark original stakeholder intentions and aspirations against the reality of current performance. Decisions w ....Making better decisions about built assets: learning by doing. This research will assist the built environment professions and their clients to make better decisions about new developments through a novel 'learning by doing' approach. Used successfully in other fields such as natural resource management, this idea will capitalise on the large number of asset investments undertaken to benchmark original stakeholder intentions and aspirations against the reality of current performance. Decisions will be re-evaluated in the context of contemporary economic, social and environmental criteria to enable existing multi-criteria models to deliver more sustainable outcomes that are also feasible and in the national interest, and consequently minimise the industry's current exposure to future climate change.Read moreRead less
Electronically Conducting Nanofibres and Assemblies. With the use of new techniques that have just emerged in the last two years and are receiving rapidly growing interest throughout the world, this project will bring to Australia a new nanofabrication platform for making a variety of complex nanostructures. Fundamental researches on these complex nanostructures will greatly advance nanoscience. New nanotechnologies will be developed to address some world-wide challenging problems, e.g. energy ....Electronically Conducting Nanofibres and Assemblies. With the use of new techniques that have just emerged in the last two years and are receiving rapidly growing interest throughout the world, this project will bring to Australia a new nanofabrication platform for making a variety of complex nanostructures. Fundamental researches on these complex nanostructures will greatly advance nanoscience. New nanotechnologies will be developed to address some world-wide challenging problems, e.g. energy conversion and storage, chemical/biological sensing and other micro- and nanoelectronic devices. This project will bring both breakthrough science and frontier technologies for building and transforming Australian industries and help place Australia at the forefront of nanotechnology. Read moreRead less
Special Research Initiatives - Grant ID: SR0354848
Funder
Australian Research Council
Funding Amount
$20,000.00
Summary
The Australian e-Humanities Research Network: Leveraging Digital Scholarship in the Humanities. Australian humanities researchers, many of them world leaders, are increasingly adopting digital technologies to create scholarly resources in a range of disciplines. It is imperative to provide scale and focus for such diverse, innovative research. This initiative will conduct a stocktake of the infrastructure needs of researchers engaged in digital resource creation projects, and develop a roadmap f ....The Australian e-Humanities Research Network: Leveraging Digital Scholarship in the Humanities. Australian humanities researchers, many of them world leaders, are increasingly adopting digital technologies to create scholarly resources in a range of disciplines. It is imperative to provide scale and focus for such diverse, innovative research. This initiative will conduct a stocktake of the infrastructure needs of researchers engaged in digital resource creation projects, and develop a roadmap for construction and implementation of a Network to address these needs. The Australian e-Humanities Research Network will take up the challenges and opportunities of digital technologies by addressing humanities researchers? requirements for training, networking, and best-practice information and advice.Read moreRead less
Uncertain Information Processing for Situation Awareness and Dynamic Decision-Making in Emergency Management. The Australian national counter-terrorism committee indicates that Australia should have a strong intelligence-led prevention and preparedness to support Australia on risk management, emergency services and maintaining capabilities to manage various types of terrorist attacks. The proposed situation awareness support technique can be used to develop situation analysis software systems or ....Uncertain Information Processing for Situation Awareness and Dynamic Decision-Making in Emergency Management. The Australian national counter-terrorism committee indicates that Australia should have a strong intelligence-led prevention and preparedness to support Australia on risk management, emergency services and maintaining capabilities to manage various types of terrorist attacks. The proposed situation awareness support technique can be used to develop situation analysis software systems or directly support Australia government agencies and industries to correctly assess a situation, increase awareness for crisis problems, and therefore improve emergency management and decision-making effectiveness, in particular, for avoiding disaster problems in the first place and preparing plans for those that undoubtedly will occur. Read moreRead less
Literary Self-Awareness and Parental Love: Challenging Alterity in Contemporary Medieval Studies. Did medieval women write about themselves as gendered individuals? Did medieval parents love their children? Despite both popular and academic opinion to the contrary, this project aims to demonstrate that these propositions are true. By studying the self-aware writings of Latin-literate medieval women and medieval parent-child advice-texts, this project aims to challenge the alterity, or otherness, ....Literary Self-Awareness and Parental Love: Challenging Alterity in Contemporary Medieval Studies. Did medieval women write about themselves as gendered individuals? Did medieval parents love their children? Despite both popular and academic opinion to the contrary, this project aims to demonstrate that these propositions are true. By studying the self-aware writings of Latin-literate medieval women and medieval parent-child advice-texts, this project aims to challenge the alterity, or otherness, of the Middle Ages, a concept which suggests that medieval people are fundamentally unlike us. In doing so, it questions the significance of alterity in the construction and practices of contemporary Medieval Studies and offers insights into possible new methodologies for the discipline.Read moreRead less
The challenge to member based organisations and their responses. The project will explore participants' construction of the meaning of membership in member based organisations (MBOs), and will carry out comparative analysis of MBOs' responses to membership decline, to identify common challenges and innovative responses. This will enhance Industry Partners' knowledge of members' motivations, and disincentives to membership, and outline examples of good practice in other fields. The results will o ....The challenge to member based organisations and their responses. The project will explore participants' construction of the meaning of membership in member based organisations (MBOs), and will carry out comparative analysis of MBOs' responses to membership decline, to identify common challenges and innovative responses. This will enhance Industry Partners' knowledge of members' motivations, and disincentives to membership, and outline examples of good practice in other fields. The results will offer practical strategies for improved member recruitment and retention in MBOs, which continue to play a significant role in Australian economic and social life. The research will make significant contributions to existing bodies of social capital and voluntary association theory.Read moreRead less