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
Investigation Into The Alternative Splicing Of Steroid Hormone Regulated Genes In Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Steroid hormones have imortant roles in breast tissue growth and differentiation. We have identified several proteins called PRMT6 and CAPER's , that are involved in steroid hormone signaling and control the alternative splicing of RNA, the process in which several different proteins can be produced from a single gene. Our aim is to study these proteins in an effort to understand how they influence alternative splicing and to identify genes they control in relation to breast cancer.
Molecular And Cellular Studies Of The Copper-transporting ATPases Affected In Menkes And Wilson Diseases
Funder
National Health and Medical Research Council
Funding Amount
$558,300.00
Summary
Copper is an element that is essential for life but is highly toxic in excess. Because of this, the regulation of copper uptake, distribution in the body and excretion of excess is a very tightly regulated process. Until recently little was known about the molecular basis of this process. Two genetic disorders that show these two aspects of copper are Menkes disease (deficiency) and Wilson disease (toxicity). Both diseases are caused by mutations in similar copper pumping proteins. Our research ....Copper is an element that is essential for life but is highly toxic in excess. Because of this, the regulation of copper uptake, distribution in the body and excretion of excess is a very tightly regulated process. Until recently little was known about the molecular basis of this process. Two genetic disorders that show these two aspects of copper are Menkes disease (deficiency) and Wilson disease (toxicity). Both diseases are caused by mutations in similar copper pumping proteins. Our research is trying to establish the molecular mechanisms used in the body to control copper metabolism. We made a major breakthrough in 1993 with the isolation of the gene affected in Menkes disease, and we continue to be one of the leading groups in the world in studying the molecular mechanisms that handle copper, and the importance of these mechanisms in health and disease. Research into the biology of copper has become much more important following the recent discoveries of the involvement of the metal in such important neurodegenerative conditions such as Alzheimer's, Mad Cow, and Parkinson's diseases. Health effects from the lack of copper may be widespread also, copper deficiency is suspected to contribute to some common diseases, such as cardiovascular problems and osteoporosis. Our research is providing information about copper transport mechanisms that are necessary for the understanding of, and may lead to better treatment and diagnosis of common and important diseases. In this grant we propose to continue our studies into the molecular signals that control the copper pumps, that make the regulation of copper metabolism possible. We also will use various test systems for studying the effect of mutations on the activity of these proteins and relate these effects to the type of disease produced in patients.Read moreRead less