Defining Genetic And Epigenetic Variation During Early Development
Funder
National Health and Medical Research Council
Funding Amount
$996,075.00
Summary
We all began life with a set of genes inherited from our parents. However, it's now known that from the time we were in the womb onwards that genes can be turned off and on by the environment or even completely lost or gained. Even what your mother ate or how she behaved while she was pregnant could have influenced your future health. Because people are so different, we are studying the subtle differences between twins to tease out the factors that may influence our genes and our health.
Improving Medication Safety In Seniors: A Cross-Jurisdictional Linkage Project
Funder
National Health and Medical Research Council
Funding Amount
$636,717.00
Summary
The project will identify priorities for tackling the current epidemic of hospitalisation of Australians aged 65+ years due to side effects of their medications. Two different groups of medications will be investigated. The first will be the prescribed drugs most often recorded as causes of hospital stay, including those taken to stop blood clotting, for high blood pressure and other cardiovascular problems, for rheumatism or strong pain relief, anti-cancer drugs and steroids. The study will exa ....The project will identify priorities for tackling the current epidemic of hospitalisation of Australians aged 65+ years due to side effects of their medications. Two different groups of medications will be investigated. The first will be the prescribed drugs most often recorded as causes of hospital stay, including those taken to stop blood clotting, for high blood pressure and other cardiovascular problems, for rheumatism or strong pain relief, anti-cancer drugs and steroids. The study will examine which of these drugs taken under what circumstances has the highest risk, so prevention can be better targeted. The study will investigate if adequate laboratory monitoring of the anti- clotting drugs is taking place and whether the guidelines should be updated. The second group will be 68 medications that should be avoided in seniors according to an international expert panel. The research will see how often these 'inappropriate medications' are still prescribed in the Australian setting, and the size of their contributions to unplanned hospital stays. The researchers suspect that this problem is much larger than immediately apparent from routine statistics, because many of the side effects of inappropriate medications are non-specific, such as confusion, drowsiness or difficulty standing up, thus putting seniors at risk of falls and neglect of other aspects of their health. The study will use a unique and new Australian research facility, which has brought together health data on the entire population of WA from both the State and Commonwealth levels, including information on pharmaceuticals, Medicare use, hospital stays and deaths. The facility works in such a way as to preserve patient and GP privacy. A strong feature of this research will be the degree of involvement of a representative and voluntary group of older Australian patients who attend GP clinics, and the GPs themselves, in advising the researchers on what's important to consumers and GPs.Read moreRead less
Studies On The Expression Of Muscarinic Receptors: Implications For The Pathology Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$498,791.00
Summary
Schizophrenia is a severe psychiatric disorder that affects approximately 1% of the population. This project will help define changes in the molecules in the brain of subjects with schizophrenia which are likely to be involved in two symptoms of the disorder, the psychoses and cognitive deficits. Understanding the cause of the cognitive deficits of schizophrenia is a high priority because they are the most disabilitating symptom of the disorder and do not respond to current drug treatments.
A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?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.
Climate Change And Rural Communities: Integrated Study Of Physical And Social Impacts, Health Risks And Adaptive Options
Funder
National Health and Medical Research Council
Funding Amount
$611,599.00
Summary
Rural Australia has begun to experience climate change impacts - which will increase in future. Losses in farm yields, water supplies, property, community morale and family incomes have diverse health effects. We will study the separate and joint effects of climate change and associated extreme events (e.g., bushfires) on selected health outcomes. Using integrative methods, we will clarify the main influences on health risks, their future projections, and how best to intervene to lessen risks.
Which Mental Activities And When For Dementia Prevention? The Four Nations Longitudinal Collaboration
Funder
National Health and Medical Research Council
Funding Amount
$183,218.00
Summary
We will examine the link between lifetime participation in complex mental activities and long term dementia risk in a level of detail not previously possible. Four major studies of brain health from around the world will join forces for the first time to determine which mental activities are most closely linked to protection from dementia, and when during the lifespan these are most important. Mental activity will be assessed using our recently published Lifetime of Experiences Questionnaire.
Role Of Transition Metal Ions And Redox Activity In The Development Of Atherosclerotic Plaques
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability ....Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability to generate free radicals is controversial. This study will employ a novel, minimally-invasive, technique to assess the nature and quantity of metal ions present in well-defined human and animal lesions at different stages of lesion development. The ability of these metal ions to catalyse free radical formation from components present in the artery wall will also be assessed. The release of these metal ions from the artery wall to added organic molecules will be assessed as this might minimise their potential to cause damage, and provide a possible therapeutic strategy. These studies will therefore provide valuable information as to the significance and role of reactive metal ions in the development of human artery disease and the possible prevention, or minimisation, of such processes.Read moreRead less
Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably e ....Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably extend the information potential of the genetic code. In addition, it is now established that chromatin structural features can influence gene expression. In vitro studies support a model in which chromatin functions as a barrier for the access to DNA. Therefore this organization has to be tighly regulated and dynamic to allow the protein-DNA interactions critical for nuclear functions. Importantly genome organisation provides in addition to genetic information another layer of information, so called epigenetic, which by definition means that it is stably inherited throughout cellular divisions, yet it is not encoded genetically. Thus each cell type will display a specific epigenome. We have recently constructed small human minichromosomes, which are much easier to study than the much larger normal chromosomes. The present project proposes to define the epigenetic feature across an entire human chromosome using our minichhromosomes as working models. The outcome will be a significant gain in our knowledge on the processes underlying epigenetic regulation, the organisation of specialised chromatin domain, and behaviour of the chromosomes.Read moreRead less
A Population-based Cohort Investigation Of Postnatal Microbial Experience, Immune Programming And Allergic Disease Risk
Funder
National Health and Medical Research Council
Funding Amount
$1,511,471.00
Summary
This is a population-based longitudinal investigation of the early life host-environment interactions that influence development of the immune system, and the risk of allergic disease. Importantly, this is one of the first studies designed to examine epigenetic programming of the infant immune system in the population setting. Thus we will be able to conduct robust tests of several critical hypotheses that will inform the prevention of allergic disease.