Roles Of Enzymes Of The Dipeptidyl Peptidase Gene Family In Human Liver
Funder
National Health and Medical Research Council
Funding Amount
$79,750.00
Summary
Chronic liver diseases, particularly those caused by autoimmune disease, alcohol and Hepatitis B and C virus infection, are major causes of morbidity and mortality in our community. They are characterised by progressive scarring of the liver which finally leads to liver failure and the need in many cases for organ transplantation. Each year 15,000 Australians become infected, probably for life, with hepatitis C virus. Unless more effective treatments are developed approximately 20% of these infe ....Chronic liver diseases, particularly those caused by autoimmune disease, alcohol and Hepatitis B and C virus infection, are major causes of morbidity and mortality in our community. They are characterised by progressive scarring of the liver which finally leads to liver failure and the need in many cases for organ transplantation. Each year 15,000 Australians become infected, probably for life, with hepatitis C virus. Unless more effective treatments are developed approximately 20% of these infections will progress to liver failure or liver cancer within 30 years. Diabetes afflicts 150 million people, and 90% have Type 2 diabetes. We request funding of our research on a family of enzymes highly prospective as targets for novel therapies for these diseases. We are internationally recognised experts on this enzyme family and on liver disease. The prototype member of this enzyme family, dipeptidyl peptidase (DP) IV, is being targeted by novel drugs that are in phase III clinical trials for Type 2 diabetes. Family member fibroblast activation protein (FAP) is targeted by novel anti-cancer drugs We were first to clone and lodge patent applications for two new enzymes of this family, DP8 and DP9. Our research proposal would lead to determination of whether FAP, DP8 and-or DP9 are valuable targets for novel liver disease therapeutics and facilitate generating the development of such therapeutics by a more thorough understanding of the activities and roles of these enzymes Completion of this project will greatly increase our understanding of these enzymes and their roles in chronic liver injury. This work can potentially lead to the development of specific inhibitors of enzyme function designed to relieve liver damage.Read moreRead less
THE DETECTION AND MANAGEMENT OF DEMENTIA IN GENERAL PRACTICE.
Funder
National Health and Medical Research Council
Funding Amount
$499,977.00
Summary
This research aims to examine a new method and practice guidelines for detection of early dementia. General practitioners will be screened on their ability to diagnose and manage dementia and to distinguish it from other diseases. Patient outcomes - including quality of life, depression, and satisfaction with care and referral indicators - will be examined.
Cognitive Outcome And Therapeutic Interventions For Coronary Artery Disease.
Funder
National Health and Medical Research Council
Funding Amount
$392,104.00
Summary
Dementia is recognized as an increasingly important factor affecting quality of life as people age. Deaths from heart disease are declining, in part due to improved surgical techniques and to the use of less invasive methods to keep arteries open such as coronary stenting. It is now well known that 20 to 60% of patients experience some degree of impairment in thinking ability (cognitive impairment) after cardiac surgery, that this will persist in some of these individuals for years and may incre ....Dementia is recognized as an increasingly important factor affecting quality of life as people age. Deaths from heart disease are declining, in part due to improved surgical techniques and to the use of less invasive methods to keep arteries open such as coronary stenting. It is now well known that 20 to 60% of patients experience some degree of impairment in thinking ability (cognitive impairment) after cardiac surgery, that this will persist in some of these individuals for years and may increase the risk of long-term problems. Cognitive impairment affects people in many ways. While it is not yet known whether the occurrence of cognitive impairment predisposes to dementia, it is thought that Mild Cognitive Impairment (MCI) may do so. We propose to explore the link between MCI and Post Procedural Cognitive Deficit (PPCD) in patients with coronary disease from before the first point of objective diagnosis, i.e. prior to the coronary angiogram, and over a 12-month period, through and subsequent to further treatment interventions such as stenting or cardiac surgery. Our Pilot data suggest that PPCD does indeed occur after angiography, and we propose to identify how long this lasts, whether MCI predisposes to it and whether it is better to wait until it resolves before further interventions are undertaken. In this way we hope to identify the safest treatment strategy for patients with coronary disease that will minimize the occurrence of Cognitive Deficit and possibly longer-term cognitive changes after investigation and treatment for their symptoms.Read moreRead less
Self Adjuvanting CTL-Based Influenza Vaccines For Human Use
Funder
National Health and Medical Research Council
Funding Amount
$214,842.00
Summary
This project will generate novel vaccines that elicit cell-mediated immunity against influenza infection. The vaccines are totally synthetic and therefore not constrained by the limitations in manufacturing which currently confront egg-grown vaccines. These vaccines induce very strong immune responses because they target dendritic cells which are pivotal for induction of all immune responses. This targeting capability is due to a simple lipid molecule incorporated into the vaccine which is recog ....This project will generate novel vaccines that elicit cell-mediated immunity against influenza infection. The vaccines are totally synthetic and therefore not constrained by the limitations in manufacturing which currently confront egg-grown vaccines. These vaccines induce very strong immune responses because they target dendritic cells which are pivotal for induction of all immune responses. This targeting capability is due to a simple lipid molecule incorporated into the vaccine which is recognised by specific receptors on the surface of dendritic cells and also causes their maturation, a step which is essential for recognition by the immune system of potential pathogens. The technology to design and assemble these new vaccines is already.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
Loss of insulin-producing beta cells leads to type 1 diabetes and rejection of allogeneic islet transplants. The aim of this program is to discover ways of protecting beta cells from damage. We will do this by investigating whether blocking crucial regulators of cell death can protect mouse and human beta cells from destruction in vitro and in vivo. In doing so, we aim to prevent diabetes in mice and potentially improve the survival of islet grafts after transplantation.
Enhancing Mental Health In Aboriginal People: Reducing Violence And Developing Resilience
Funder
National Health and Medical Research Council
Funding Amount
$1,771,151.00
Summary
This project aims to determine the best ways to improve the Social Emotional Well Being (SEWB) of the Aboriginal people of Broken Hill, Menindee and Wilcannia. This project will develop a culturally appropriate and evidenced based intervention to break the cycle of ongoing grief, mental illness, alcohol and other drugs and violence. The project will proceed in a number of interrelated phases including extensive community consultations and a baseline survey. The project will then implement and ev ....This project aims to determine the best ways to improve the Social Emotional Well Being (SEWB) of the Aboriginal people of Broken Hill, Menindee and Wilcannia. This project will develop a culturally appropriate and evidenced based intervention to break the cycle of ongoing grief, mental illness, alcohol and other drugs and violence. The project will proceed in a number of interrelated phases including extensive community consultations and a baseline survey. The project will then implement and evaluate an intervention program that provides a community and individual program that adopts evidence-based approaches and modifies them to be acceptable within Aboriginal communities. These interventions aim to break the cycle of violence and mental health problems by teaching adaptive skills to reduce violent behaviours and by providing mental health interventions that reduce disorders that contribute to violence.Read moreRead less
The Pacific OPIC Study - A Four Country Study Of Obesity Prevention In Communities
Funder
National Health and Medical Research Council
Funding Amount
$1,600,580.00
Summary
Obesity is a rapidly escalating, worldwide epidemic. Many countries recognise the need to prevent obesity but there is insufficient evidence about what interventions work. The Pacific Obesity Prevention in Communities (OPIC) Project will provide data on the effectiveness of a range of interventions to prevent obesity among young people in Fiji, Tonga, New Zealand and Australia. Prevention research is particularly required in countries such as Fiji and Tonga because their prevalence of obesity is ....Obesity is a rapidly escalating, worldwide epidemic. Many countries recognise the need to prevent obesity but there is insufficient evidence about what interventions work. The Pacific Obesity Prevention in Communities (OPIC) Project will provide data on the effectiveness of a range of interventions to prevent obesity among young people in Fiji, Tonga, New Zealand and Australia. Prevention research is particularly required in countries such as Fiji and Tonga because their prevalence of obesity is extremely high. The interventions used in this project will be culturally appropriate and include at least 1000 young people in each intervention group. The outcomes of this project will be applicable to both low- and high-income countries. This project will lead to a greater understanding of the socio-cultural, policy, and economic contexts and provide crucial evidence for public health action to prevent obesity.Read moreRead less