Cryptococcal Meningoencephalitis - Fungal Determinants Of Invasion Of The CNS
Funder
National Health and Medical Research Council
Funding Amount
$587,634.00
Summary
Meningitis and brain infection (meningoencephalitis) due to the fungus Cryptococcus, affect over 1 million patients with AIDS annually, especially in developing countries; with more than 600,000 deaths. It is not known how Cryptococci cross from the blood stream into the brain; this must be elucidated in order to prevent and/or control this devastating infection. This project will determine how cryptococci influence host blood cells to act as “Trojan horses” and/or release products that initiate ....Meningitis and brain infection (meningoencephalitis) due to the fungus Cryptococcus, affect over 1 million patients with AIDS annually, especially in developing countries; with more than 600,000 deaths. It is not known how Cryptococci cross from the blood stream into the brain; this must be elucidated in order to prevent and/or control this devastating infection. This project will determine how cryptococci influence host blood cells to act as “Trojan horses” and/or release products that initiate invasion of brain tissue and meningitis.Read moreRead less
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
Mechanisms And Therapies In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,360,700.00
Summary
Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting ....Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting new knowledge through integrated research.Read moreRead less
The Older Australian Twins Study (OATS) Of Healthy Brain Ageing And Age-related Neurocognitive Disorders
Funder
National Health and Medical Research Council
Funding Amount
$940,960.00
Summary
Ageing is associated with cognitive decline and dementia. It is still not completely understood what relative contributions genes and environment play in these. This project is an extension of the Older Australian Twins Study to examine genetic and environmental factors associated with late life brain changes and dementia, and will establish an internationally significant cohort for novel discovery.
Molecular Regulation Of CRH Gene Expression In The Human Placenta
Funder
National Health and Medical Research Council
Funding Amount
$70,285.00
Summary
Approximately 70% of infant death is a result of premature birth. Preterm delivery occurs in 6-10% of pregnancies, and there has been no reduction in this rate in the last 30 years. This is largely because we remain ignorant of how normal and preterm birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotropin releasing hormon ....Approximately 70% of infant death is a result of premature birth. Preterm delivery occurs in 6-10% of pregnancies, and there has been no reduction in this rate in the last 30 years. This is largely because we remain ignorant of how normal and preterm birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotropin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely the rise in CRH production occurs earlier and more rapidly, while in women who deliver late the rise occurs more slowly. This work has led to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done by examining the DNA sequences involved in controlling the CRH gene and by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and preterm birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be developed.Read moreRead less
Improved Formulations Of Anti-cancer Agents 5-Fluorouracil And Oxaliplatin Using Excipient Technology
Funder
National Health and Medical Research Council
Funding Amount
$202,973.00
Summary
Chemotherapy plays a key role in cancer treatment, however, problems persist with severe adverse toxic effects. Combinations of anti-cancer agents give better results, but these agents still have major negative effects, for example, on veins and peripheral nerves and they must be given separately. We have developed a novel, all-in-one formulation of Oxaliplatin with 5-Fluorouracil and Leucovorin, with the potential for fewer toxic effects and improved patient care.
BRIDGET: BRain Imaging, Cognition, Dementia And Next Generation GEnomics: A Transdisciplinary Approach To Search For Risk And Protective Factors Of Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,081,489.00
Summary
Alzheimer’s disease (AD) begins many years before diagnosis and yet its aetiology is still poorly understood. The BRIDGET consortium aims to identify genetic variants that are associated with structural brain ageing, cognitive performance, and dementia risk in richly phenotyped international and Australian population-based samples. This work aims to provide crucial information on the molecular pathways leading to AD, potentially leading to improved health outcomes for our ageing population.
Osteoporosis is a major and increasing public health problem. Fracture, the ultimate consequence of osteoporosis is associated with significant morbidity, mortality and economic costs. The Dubbo Osteoporosis Epidemiology Study, starting in 1989, with over 2000 women and men, is one of the longest running epidemiological studies in osteoporosis worldwide. It has been at the forefront of epidemiological advances in osteoporosis. It has identified osteoporotic fracture risks including low bone dens ....Osteoporosis is a major and increasing public health problem. Fracture, the ultimate consequence of osteoporosis is associated with significant morbidity, mortality and economic costs. The Dubbo Osteoporosis Epidemiology Study, starting in 1989, with over 2000 women and men, is one of the longest running epidemiological studies in osteoporosis worldwide. It has been at the forefront of epidemiological advances in osteoporosis. It has identified osteoporotic fracture risks including low bone density and bone loss, muscle weakness and postural instability, as well as the extent of the problem in men, and the significant costs, ill-heath and mortality associated with fracture. Despite the clarification of risk factors over the past decade, there are significant gaps in knowledge about osteoporosis, particularly in the accurate prediction of fracture risk and in identification of factors related to fracture-associated mortality and survival post fracture. Although bone density is one of the best predictors of fracture risk, it incompletely discriminates between those who will fracture from those who will not. Although a number of clinical risk factors, and other measures of bone strength, such as quantitative ultrasound and geometry, have been shown to be independent predictors of fracture risk, it is not clear that these measures can be integrated with BMD to improve fracture prediction. The aim of the current study, is to develop and validate models using bone density, other measures of bone strength and clinical parameters that will more accurately predict fracture risk and mortality following fracture in older men and women. The more precise identification of those at high risk of fracture and at risk for poor outcomes following fracture will provide a rational basis for the development of more cost effective interventions for prevention of fracture and its associated morbidity and mortality.Read moreRead less
Identification Of Heterogeneity In Vasodilator Function In Human And Rat Resistance Vessels: Potential Drug Targets?
Funder
National Health and Medical Research Council
Funding Amount
$595,330.00
Summary
The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not w ....The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not well understood. While current drugs for treating vascular disease either reduce vessel constriction or increase dilation, they are not specific for individual arteries; a situation that would allow us to control vascular diseases in a very specific manner. Recently, we have described differences between the ways that individual vessels are controlled. These changes relate to differences in the way that different vessels dilate. AIMS - To further understand normal blood vessel function and the changes that occur in blood vessels in cardiovascular disease, with a focus on the ways that blood vessels dilate in normal states and in obesity-related diseases, such as in hypertension and diabetes. - The eventual aim is to identify the specific ways that arteries function, so that artery-specific drug targets can be identified to treat disease-related changes in cardiovascular disease in a very specific manner. EXPECTED OUTCOMES This project will contribute to understanding blood vessel function in health and disease. The expected eventual outcome is the identification of the mechanisms that underlie the function of different arteries in different parts of the body, so that specific individual vessel function can be targeted to treat vascular disease. Additionally, this work will also verify the relevance of the diet-induced obesity animal model, in terms of the characteristics and causes of human obesity and related cardiovascular disease.Read moreRead less