Neuroscience On Barriers In Development (NEUROBID)
Funder
National Health and Medical Research Council
Funding Amount
$600,927.00
Summary
The program aims to understand normal and disturbed brain barrier function in development to devise ways of preventing or ameliorating neurological conditions in infants or adult neurological disorders with developmental origins. Unique features of transport mechanisms across brain barriers will be used to design novel methods of targeting therapeutic macromolecular and cellular agents to the brain barriers and transporting them into brain for treatment of neurological diseases in young and old.
Hypoglycaemia In Young Patients With Type 1 Diabetes: Pathophysiology, Predisposition And Preventive Strategies
Funder
National Health and Medical Research Council
Funding Amount
$2,680,000.00
Summary
The vision of this proposal is to bring together an active team of experienced investigators that will address important clinical problems affecting the management of children and adolescents with type 1 diabetes. Along with facilities and resources already under development, the program will further establish a core of investigators dedicated to patient centred and clinical research that will facilitate scientific advances to be put into practice. The incidence of type 1 diabetes is continuing ....The vision of this proposal is to bring together an active team of experienced investigators that will address important clinical problems affecting the management of children and adolescents with type 1 diabetes. Along with facilities and resources already under development, the program will further establish a core of investigators dedicated to patient centred and clinical research that will facilitate scientific advances to be put into practice. The incidence of type 1 diabetes is continuing to increase particularly in the young. As we enter the 21st century, insulin treatment aimed at restoring blood glucose levels as close to the normal as possible remains the most effective way to prevent the devastating long-term complications of the disease. Unfortunately this is difficult to achieve largely because insulin therapy is frequently associated with the development of low blood glucose or hypoglycaemia. Hyperglycaemia results in unpleasant symptoms if mild but if severe it can produce convulsions or unconsciousness. The fear of hypoglycaemia is ever present for the patient and their family, this not only significantly impairs quality of life but importantly also severely restricts attempts to control diabetes. One of the major goals of this research program will be to address important unanswered questions related to the development of hyperglycaemia in children and adolescents with diabetes. The research team will examine in detail the protective physiological mechanisms against hyperglycaemia that are deranged in diabetes, they will also study more closely those situations that are known to predispose to hyperglycaemia such as sleep and exercise as well as how the brain is affected as blood glucose falls. By taking this approach we hope to be able to devise management strategies that will lessen the impact of hyperglycaemia in diabetes treatment. It is anticipated that this in turn will contribute to the prevention of diabetes complications as well as reduce the burden of the disease for the patient and his or her family. A second goal of this research program will be to develop an internationally unique resource that will be available to all diabetes investigators. We will build on an already established population based database of all the children and adolescents with diabetes in Western Australia as well as complete a DNA bank of these patients and their families. Thus in addition to bringing together an effective team of researchers, this program will further develop resources that can be central to addressing other important questions related to the causes of diabetes and its complications.Read moreRead less
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
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
Early Intervention To Prevent Childhood Obesity Among A Disadvantaged Population: A Home-based Randomised Controlled Tri
Funder
National Health and Medical Research Council
Funding Amount
$675,082.00
Summary
This intervention research will conduct a randomised controlled trial, of a community-based early childhood home visiting intervention designed to improve family and behavioural risk factors for childhood obesity and overweight. This intervention which will be developed in collaboration with the Health Promotion Unit, Child and Family Health Nurses, university academic experts and mothers in the community promises to deliver significant health and social benefits, in particular, preventing early ....This intervention research will conduct a randomised controlled trial, of a community-based early childhood home visiting intervention designed to improve family and behavioural risk factors for childhood obesity and overweight. This intervention which will be developed in collaboration with the Health Promotion Unit, Child and Family Health Nurses, university academic experts and mothers in the community promises to deliver significant health and social benefits, in particular, preventing early onset of childhood obesity. It will result in a series of recommendations for policies and practical methods for promoting healthy feeding and physical activity of infants under two years of age with particular application to families who are socially and economically disadvantaged. These policies and practical methods for preventing childhood obesity could be used across Australia.Read moreRead less
Chimeric Virus-like Particles (VLPs) Displaying H1, H3 And H5 Haemagglutinins - Construction And Immunogenicity
Funder
National Health and Medical Research Council
Funding Amount
$207,543.00
Summary
Virus-like particles (VLPs) provoke strong immune responses in the body. We have developed a novel VLP system that allows the production of VLPs containing foreign vaccine antigens of much larger size than previously possible, and have shown that these VLPs provoke strong immune responses in mice without the use of adjuvants. The capacity of these VLPs is large enough to accommodate the most important vaccine antigen of influenza, the haemagglutinin (HA) molecule. We will test whether VLPs can b ....Virus-like particles (VLPs) provoke strong immune responses in the body. We have developed a novel VLP system that allows the production of VLPs containing foreign vaccine antigens of much larger size than previously possible, and have shown that these VLPs provoke strong immune responses in mice without the use of adjuvants. The capacity of these VLPs is large enough to accommodate the most important vaccine antigen of influenza, the haemagglutinin (HA) molecule. We will test whether VLPs can be produced containing each of the three most important HA types _ H1 and H3 that are currently circulating in man, and H5 (avian) that is considered a pandemic threat. VLPs will be tested for their ability to induce neutralizing antibody and cellular immune responses in mice, and for their ability to protect ferrets from influenza infection. If successful, the HA-VLP system would provide a method for the rapid production of new influenza vaccines using large-scale fermentation technology as for hepatitis B and many other vaccines, rather than eggs or cell culture as used for current influenza vaccines.Read moreRead less
Assessment Of Alpha-galactosylceramide As A Novel Adjuvant For Pandemic Influenza: A Virua Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$220,042.00
Summary
The occurrence of human infections with pathogenic avian H5N1 Influenza A viruses was the first documentation of these viruses demonstrating an ability to directly transmit from birds to humans. The virulent nature of these infections, and the fact that there is no pre-existing immunity to these viruses in the human population has raised the concern that these viruses may emerge to cause the next influenza pandemic. Vaccination is our most effective way of protecting against influenza infection, ....The occurrence of human infections with pathogenic avian H5N1 Influenza A viruses was the first documentation of these viruses demonstrating an ability to directly transmit from birds to humans. The virulent nature of these infections, and the fact that there is no pre-existing immunity to these viruses in the human population has raised the concern that these viruses may emerge to cause the next influenza pandemic. Vaccination is our most effective way of protecting against influenza infection, however there are no commercially available avian influenza vaccines available. Moreover, recent evidence suggests current vaccines strategies may be less than effective. This proposal aims to evaluate the efficacy of a novel vaccine strategy that promotes immune protection against a potential pandemic influenza strain.Read moreRead less
They aim to create insulin-secreting B cells by identifying their progenitor cells and the moleculaes normally required for their development, in order to restore B-cell function in the people with type 1 diabetes. Mouse and human multipotent embryonic stem (ES) cells and fetal mouse panceas and adult pancreas duct cells will be used as sources of progenitor B cells. Comparative studies will provide a more complete picture of human B-cell ontogeny. Culture systems developed for ES cells-embryoid ....They aim to create insulin-secreting B cells by identifying their progenitor cells and the moleculaes normally required for their development, in order to restore B-cell function in the people with type 1 diabetes. Mouse and human multipotent embryonic stem (ES) cells and fetal mouse panceas and adult pancreas duct cells will be used as sources of progenitor B cells. Comparative studies will provide a more complete picture of human B-cell ontogeny. Culture systems developed for ES cells-embryoid bodies (EB) - EB-derived cells, fetal pancreas and adult pancreas duct cells, will be employed to screen for and identify novel growth-differentiation factors and to optimise parameters for creating B cells in vitro or (re) generating B cells in vivo. Genetic constructs allowing regulated expression of fluorescently-tagged marker genes and growth-transcription factors will be introduced into cultured cells or transgenic mice to enable progenitor B cells to be tracked and isolated. Progenitor B cells will be typed with panels of known novel markers molecules at the gene and protein level, and gene expression profiles of tissue yielding B cells will be analysed across time to reveal further candidate markers. Molecules and methods effective in mouse systems will be applied to human ES cell-derived or pancreatic duct cells. The capacity to progenitor cells or insulin-secreting cells to ameliorate diabetes when transplanted into the testis, under the kidney capsule or into the pancreas of mouse models would represent proof-of-concept. Functional B cells derived from human ERS cells or pancreas duct cells, or growth factors that regenerate B cells in vivo, could together with appropriate immunotherapy restore B-cell function in people with type 1 diabetes.Read moreRead less