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
Endocrine And Molecular Regulation Of Placental CRH Expression
Funder
National Health and Medical Research Council
Funding Amount
$466,980.00
Summary
Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal 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 (corticotr ....Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal 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 (corticotrophin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely a rise in CRH occurs earlier in the pregnancy and more rapidly, while in women who deliver late the rise occurs more slowly. This work has given rise 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 research project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done in two ways: (1) by examining the DNA sequences involved in controlling expression of the CRH gene and (2) 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 abnormal birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be invented.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.
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
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Dual Targeting Of The Androgen Receptor For Effective And Durable Control Of Lethal Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$946,177.00
Summary
Preventing binding of androgens to the androgen receptor is the mainstay treatment for advanced prostate cancer, but resistance inevitably develops and the disease becomes lethal. We will develop a new drug that targets a part of the androgen receptor unrelated to its androgen binding function to overcome resistance to current therapy. As this drug will be effective in all stages of prostate cancer, it has high potential to improve survival outcomes for men with prostate cancer.
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