Enhancing Peripheral Clearance Of Beta Amyloid As A Treatment For Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$548,681.00
Summary
Amyloid-beta (abeta) accumulation in the brain is a key step in the development of Alzheimer's disease, with potential therapies focusing on its clearance. Compounds that bind abeta in blood have been shown to alter brain abeta levels. We will assess the efficacy of a novel abeta-binding peptide to promote peripheral clearance of brain-derived abeta in a mouse model of AD. Such a drug would be effective in sporadic AD, where the efflux transport, clearance and degradation systems are defective.
Developmental Origins Of Adult Cardiovascular Disease: Vascular Health In The Raine Cohort
Funder
National Health and Medical Research Council
Funding Amount
$1,087,427.00
Summary
The Raine study is a unique long term experiment that has collected extensive pre-birth and childhood data in ~3000 young Australians, who are now 27 years old. We plan to measure the artery health of 1200 of these volunteers and to determine what factors, both before and after birth, influence the presence of early atherosclerosis in humans. This study will guide strategies aimed at early prevention of heart attacks and stroke in humans, by defining the major risk factors.
National Centre Of Research Excellence To Improve Management Of Peripheral Arterial Disease
Funder
National Health and Medical Research Council
Funding Amount
$2,618,637.00
Summary
Approximately 15% of adults have blockages or weakness of major arteries in the periphery, associated with impaired quality of life and a high mortality. Significant management deficiencies for these problems include limited diagnostic, prognostic and treatment options, as well as poor adoption of evidence based practice. The proposed national centre will bring together a group of experts in the field to instigate a number of initiatives to improve patient management.
Transcriptional Control Of Blood Vessel Development By Sox18
Funder
National Health and Medical Research Council
Funding Amount
$468,564.00
Summary
Blood vessels play an essential role in maintaining the supply of nutrients to every organ and tissue in the body. Improper development of blood vessels in the embryo can compromise survival of the embryo, and defects in the ability of blood vessels to grow, regenerate and adapt to change during adult life can be life-threatening. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of ....Blood vessels play an essential role in maintaining the supply of nutrients to every organ and tissue in the body. Improper development of blood vessels in the embryo can compromise survival of the embryo, and defects in the ability of blood vessels to grow, regenerate and adapt to change during adult life can be life-threatening. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fundamental importance in the health sciences to gain an understanding of how blood vessels form and regenerate. As a result of our collaborative research efforts, we have discovered a gene, Sox18, that appears to regulate blood vessel development by controlling the formation and-or behaviour of endothelial cells, which line the blood vessels and make them impermeable. Our research so far indicates that MICE WITH DEFECTS IN SOX18 DIE FROM VASCULAR DEFECTS, underlining the importance of this gene. THIS PROJECT IS CONCERNED WITH FINDING OUT HOW SOX18 WORKS - exactly what goes wrong in mice lacking this gene, whether Sox18 can influence endothelial cell behaviour in cell culture, how Sox18 comes to be active in endothelial cells, what genes are switched on by Sox18, and what genes Sox18 co-operates with in its role in endothelial cells. The answers to these questions will not only provide fundamental basic information about how blood vessels development is controlled, but also sow the seeds for possible future therapies in which blood vessel development could be stimulated (eg in wound healing) or suppressed (eg in tumour progression) through pharmaceutical intervention.Read moreRead less
Exercise As Medicine For Heart Failure: A Novel Intervention To Improve Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$665,585.00
Summary
Heart failure (HF) is a common, debilitating and expensive disease; prognosis remains poorer than for the most cancers. 30,000 Australians are diagnosed every year and 300,000 live with the HF, at an annual cost of ~$1Billion. Exercise training is effective therapy in HF, because it reverses many of the problems that contribute to the reduced lifespan and impaired quality of life of patients with HF. We will test an exciting new type of exercise that promising greater benefit, at lower risk.
AusDiab 3: Emerging Risk Factors For And Long-term Incidence Of Cardio-metabolic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$2,616,397.00
Summary
This study will track 11,000 Australian adults over 12 years to determine how many develop diabetes, obesity, kidney and heart disease. The study will develop ways to best predict those who are going to develop these conditions before they have arisen, and will explore a range of novel risk factors to better understand these conditions.
The Role Of Capsid Protein Nucleolar Localisation In Chikungunya Virus: Implications For Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Chikungunya virus (CHIKV) is a globally widespread mosquito-borne alphavirus capable of causing considerable human morbidity and mortality. With no CHIKV vaccine or antiviral available this proposal aims to develop a live attenuated CHIKV vaccine, rationally designed by investigating the host cell nucleolar trafficking of CHIKV capsid protein. This vaccine has the potential to provide cross-protection against additional arthritogenic alphaviruses endemic to Australia such as Ross River virus.
A Genome-wide Search For Genes Underlying The Developmental Origins Of Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,022,552.00
Summary
Epidemic rises in the incidence of many chronic diseases such as obesity, type 2 diabetes, hypertension, coronary artery disease and mental illness have occurred in Australia over the last two decades. Antenatal, early life and childhood factors have been consistently associated with the development of such diseases. We propose to conduct a genome-wide scan in an exceptional longitudinal birth cohort in order to identify the genetic mechanisms linking early life event and adult disease.
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$827,660.00
Summary
Infections with mosquito-borne viruses are increasing at an alarming rate worldwide. Ross River virus is endemic in parts of Australia, PNG and Pacific islands, while chikungunya virus is distributed globally and causes recurrent pandemics that involve millions of people. These viruses cause severe musculoskeletal disease for several months after infection. This project aims to establish how these viruses interact with the human host to cause disease and may provide a basis for new treatments.
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$285,990.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin i ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin is down-regulated by either erythroid differentiation or the haem precursor protoporphyrin IX (Becker and Richardson, submitted). These data strongly suggest a role for frataxin in iron metabolism. In the present study we will continue to assess if frataxin plays a role in the way cells handle iron. Using a unique model of mitochondrial iron overload developed in my lab (Richardson et al. (1996) BLOOD 87:3477), we will extensively investigate the iron metabolism of the mitochondrion in order to determine the function of frataxin and its role in Friedreich's ataxia. In addition, we have developed a series of new drugs known as iron chelators that can enter the mitochondrion due to their high lipid solubility (Becker and Richardson 1999 J. Lab. Clin. Med. 134:510). These latter drugs are far more effective than the chelator currently used to treat iron overload, desferrioxamine (DFO). Indeed, our chelators have been designed to result in high iron chelation efficacy but low toxicity (see Becker and Richardson, 1999). This exciting research may be crucial in understanding the development of FA and in creating new therapies such as the use of iron chelators.Read moreRead less