The Role Of Metabolic And Inflammatory Factors In Cognitive Decline And Cerebrovascular Pathology In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$945,987.00
Summary
Metabolic factors and measures of inflammation in the body have recently been shown to influence mental function and increase the risk of developing age-related disorders such as Alzheimer’s disease. The influence metabolic factors and inflammation have on function of the ageing brain is likely to be determined by complex interplay between many factors, such as physical health, lifestyle, nutrition and our genes. By studying these factors and how they relate to one another in large groups of eld ....Metabolic factors and measures of inflammation in the body have recently been shown to influence mental function and increase the risk of developing age-related disorders such as Alzheimer’s disease. The influence metabolic factors and inflammation have on function of the ageing brain is likely to be determined by complex interplay between many factors, such as physical health, lifestyle, nutrition and our genes. By studying these factors and how they relate to one another in large groups of elderly individuals, we will be able to determine the role these factors play in brain ageing. In addition we will be able to determine an ‘at risk’ profile for elderly individuals for accelerated ageing effects. Identification of this profile is important as it will allow the development of interventions which may prevent or delay the onset of cognitive decline in late life. We plan to study the impact of metabolic and inflammatory factors on brain ageing and in two groups of elderly individuals both of which are currently being studied in detail by our research team. By using these existing groups we will minimize the costs associated with our research, but maximize the research benefit and the benefit to society. Our groups include a large community sample of elderly individuals aged 70-90 years and a large group of elderly twins aged over 65 years. Our use of twins for the study is particularly important as it will help us separate genetic and environmental influences on the measures. We will measure multiple metabolic and inflammatory factors in the body and determine their relationship to detailed tests of cognitive function and to cerebrovascular pathology on brain magnetic resonance imaging. We will look at how these factors relate to one another and which factors are most strongly associated with accelerated ageing. We will be able to follow subjects in each group over a 2 year interval to see which factors most strongly predict change in cognitive function and cerebrovascular pathology over time. Our research is unique in its inclusion of multiple factors which may affect brain ageing, its ability to look in detail at the contribution of genetic influences on metabolic and inflammatory factors, and in our planned follow-up of these individuals.Read moreRead less
Intergeneration Growth And Risk Of Metaboloc Disorders
Funder
National Health and Medical Research Council
Funding Amount
$2,095,469.00
Summary
A compelling raft of studies has now shown that low birth weight predisposes to later, impaired glucose tolerance, diabetes, cardiovascular disease, hypertension and high cholesterol. The associations are clearly evident even after adjusting for important lifestyle factors, occupation, income, adult diet and socio-economic status. This has resulted in a new paradigm for understanding the transmission of disease risk from one generation to the next. A team of researchers based at the University o ....A compelling raft of studies has now shown that low birth weight predisposes to later, impaired glucose tolerance, diabetes, cardiovascular disease, hypertension and high cholesterol. The associations are clearly evident even after adjusting for important lifestyle factors, occupation, income, adult diet and socio-economic status. This has resulted in a new paradigm for understanding the transmission of disease risk from one generation to the next. A team of researchers based at the University of Adelaide led by Dr Davies has gained international recognition for being at the forefront of this research. Thirty years ago, the group established the Lucina cohort to study intergenerational health among women, and how conditions in pregnancy can affect the reproductive health of offspring in successive generations. Dr Davies and his team of researchers will expand this study in ways that were designed at the outset, but not commenced until now. This includes enrolling the traced mothers to study how their clinical experiences in pregnancy predict their own later risk of diabetes. We will also be seeking to enrol the siblings of the daughters so that we can identify events in pregnancies that predict which sibling is at increased risk of diabetes. Finally, the study will enrol the grandchildren and trace their birth records so that we can study the relationship between diabetes risk, intergenerational growth and how that risk can be substantially influenced by factors as basic as pre-pregnancy body weight and weight gain in pregnancy. The objective of this research is to grow healthier Australian babies, children and thereby healthier adults.Read moreRead less
Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes. We will complete recruitment an ....Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes. We will complete recruitment and assessment of a cohort of 1500 postmenopausal women with either low or high bone mineral density from pre-existing population cohorts in Australia. A genomewide association study will then be performed on these cases. Associated genes in different datasets will then be investigated further in our cohort, and high-density SNP mapping performed to identify true associated variants. These studies should identify most genetic variants associated with BMD variation and low trauma fracture in the general community, allowing development of diagnostic-disease predictive genetic tests, and informing development of novel therapeutic agents for osteoporosis.Read moreRead less
The principle objective of the proposed project is to determine the molecular, cellular extracellular matrix pathology of chondrodysplasia phenotypes which result from mutations in a variety of different gene products that are important for normal bone development. To achieve our objective the Eurogrow consortium has developed an extensive series of mouse models of chondrodysplasias that closely mimic the relevant human phenotype. The consortium will use a multidisciplinary systems biology appro ....The principle objective of the proposed project is to determine the molecular, cellular extracellular matrix pathology of chondrodysplasia phenotypes which result from mutations in a variety of different gene products that are important for normal bone development. To achieve our objective the Eurogrow consortium has developed an extensive series of mouse models of chondrodysplasias that closely mimic the relevant human phenotype. The consortium will use a multidisciplinary systems biology approach to determine the molecular mechanisms that underpin the pathophysiology of these distinct chondrodysplasias. From this approach we can expect to identify common disease mechanisms and learn general principles about genotype-phenotype correlations in chondrodysplasia phenotypes. The NHMRC-EU grant is to fund a consortium (Eurogrow) of 10 EU research groups (led by the University of Manchester) along with my research group at the MCRI to conduct these integrated studies.Read moreRead less
Neonatal Immunization With Pneumococcal Conjugate Vaccine In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$1,181,966.00
Summary
One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the dev ....One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the development of immunity and response to other vaccines given to infants. This study will also provide a unique opportunity for training of PNG and Australian scientists in both countries; transfer state-of-the-art immunological technology and stimulate further collaborations on respiratory infections in the region.Read moreRead less
Novel Approaches To Pathogenesis, Diagnosis &treatment Of Autoimmune Diseases Based On New Insights Into Thymus-dependen
Funder
National Health and Medical Research Council
Funding Amount
$1,045,422.00
Summary
An individual relies upon their immune system to protect against invasion by hostile organisms. The system usually works well. Invading agents (the 'non-self') are detected and attacked by the immune system's patrolling killer T cells. These normally beneficial cells are called T cells because they were formed and educated in an organ called the thymus, which kick-starts our immune system in childhood, but falls into inactivity by adolescence. Sometimes the education system in the thymus goes wr ....An individual relies upon their immune system to protect against invasion by hostile organisms. The system usually works well. Invading agents (the 'non-self') are detected and attacked by the immune system's patrolling killer T cells. These normally beneficial cells are called T cells because they were formed and educated in an organ called the thymus, which kick-starts our immune system in childhood, but falls into inactivity by adolescence. Sometimes the education system in the thymus goes wrong and it releases T cells that mistakenly attack 'self' instead of 'non-self'. This causes autoimmune diseases, such as type1 diabetes, multiple sclerosis and rheumatoid arthritis. The Euro-Thymaide project aims to determine why and how self-attacking T cells are mistakenly released from the thymus into the body. Usually such errant T cells are detected and destroyed within the thymus, before they have the opportunity to escape and cause autoimmune diseases. The ultimate objective is to learn about the thymus recognition process and help the immune system detect and destroy faulty T cells that patrol the body, thereby preventing the onset of autoimmune diseases.Read moreRead less
Assessment Of The Effectiveness Of Australian Models Of Palliative Care Delivery In Four Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$150,000.00
Summary
This study will be conducted in three Australian states (Queensland, Victoria and West Australia), to assess the effectiveness of existing palliative care service delivery to people with motor neurone disease, multiple sclerosis, Huntington’s disease or Parkinson’s disease, and to their families. In phase I, interviews will be conducted with people who have these diseases, their families, and health professionals to discover the needs for palliative care services. In phase II, a survey will dete ....This study will be conducted in three Australian states (Queensland, Victoria and West Australia), to assess the effectiveness of existing palliative care service delivery to people with motor neurone disease, multiple sclerosis, Huntington’s disease or Parkinson’s disease, and to their families. In phase I, interviews will be conducted with people who have these diseases, their families, and health professionals to discover the needs for palliative care services. In phase II, a survey will determine the extent to which these needs are met. The findings will be used to recommend improved palliative care delivery models.Read moreRead less
Production Of Nasal Filters: Enhanced Prophylactic Protection From Aerosol Exposure
Funder
National Health and Medical Research Council
Funding Amount
$147,000.00
Summary
Influenza is a highly contagious disease that is transmitted via infective secretions containing the virus. An infected person produces tiny droplets of these secretions when coughing, sneezing, and talking, and the droplets are disseminated into the air where they are subsequently inhaled by others. A common way of preventing such transmission is to wear a mask to prevent droplet inhalation. While such masks may greatly reduce exposure, they do not eliminate it, as some viruses can pass around ....Influenza is a highly contagious disease that is transmitted via infective secretions containing the virus. An infected person produces tiny droplets of these secretions when coughing, sneezing, and talking, and the droplets are disseminated into the air where they are subsequently inhaled by others. A common way of preventing such transmission is to wear a mask to prevent droplet inhalation. While such masks may greatly reduce exposure, they do not eliminate it, as some viruses can pass around the edges of masks, particularly if it fits poorly, and also a small percentage can pass through the filter material. While influenza is usually not a major health problem in the general community, the emergence of a more hazardous strain will place an additional burden on health care and other facilities, and requires the development and optimization of measures to minimize virus spread and protect those who are exposed. The aim of this project is to build small filters that can be worn in the nose to provide additional filtration of inhaled air. These filters would be worn in combination with a mask in high exposure circumstances, such as by health care workers when treating infected patients or could be used when a mask was not normally worn to provide effective and discreet protection, such as in crowded public places. Developing such filters builds on our experience of making small samplers worn in the nose to measure allergen exposure. This experience is combined with advanced filter materials developed by leading US researchers that permit the efficient filtration of particles as small as viruses. This project will be conducted in collaboration with a leading Australian design group, and we will design and evaluate such filters for their ability to capture virus and thus protect the wearer. The filters should provide an intuitive, effective and inexpensive method to be used in combination with other hygiene measures to increase personal protection from acquiring highly transmissible respiratory diseases, particularly influenza. We expect to have prototypes of the filters available in 6 months so that production can commence.Read moreRead less