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
Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.
Establishing evidence for the functional properties of a whole grain in weight management. The successful development of functional foods relies on communicating proven effects. This project aims to prove that the food containing the satiety properties of a whole grain (OG) may help in weight management. We will conduct basic research investigating the link between consumption of OG-containing foods and the regulatory mechanisms of satiety, and test whether the satiety properties can be used to ....Establishing evidence for the functional properties of a whole grain in weight management. The successful development of functional foods relies on communicating proven effects. This project aims to prove that the food containing the satiety properties of a whole grain (OG) may help in weight management. We will conduct basic research investigating the link between consumption of OG-containing foods and the regulatory mechanisms of satiety, and test whether the satiety properties can be used to prevent, reduce and correct body weight gain in the early, middle and late stages of obesity. We will then apply this understanding in a human trial of mildly and long term overweight subjects, to aid the formulation of statements on the potential health benefits from consuming OG.Read moreRead less
Gene therapy for islet transplantation. Improved understanding of aetiology of type I diabetes. Development of islet transplantation as a clinical therapeutic for type I diabetes. Improved efficacy of islet transplantation. Improved health for subjects with type I diabetes. Decreased diabetic complications. Improved quality of life for subjects with type I diabetes. Reduced burden on health system for management of diabetic complications for subjects with type I diabetes
Development of natural herbal medicines for managing metabolic syndrome in order to prevent type 2 diabetes. Type 2 diabetes affects almost 7% of Australia~{!/~}s population. Its incidence continues to grow, as indicated by high rates of metabolic syndrome, a pre-stage of type 2 diabetes. Using novel and bio-molecular techniques, we will evaluate the effects and mechanisms of three natural compounds from anti-diabetic Chinese herbs on cellular and rodent models with metabolic syndrome. This stud ....Development of natural herbal medicines for managing metabolic syndrome in order to prevent type 2 diabetes. Type 2 diabetes affects almost 7% of Australia~{!/~}s population. Its incidence continues to grow, as indicated by high rates of metabolic syndrome, a pre-stage of type 2 diabetes. Using novel and bio-molecular techniques, we will evaluate the effects and mechanisms of three natural compounds from anti-diabetic Chinese herbs on cellular and rodent models with metabolic syndrome. This study will provide scientific evidence as to how and why herbal compounds improve insulin resistance and abnormalities in glucose and lipids metabolism. The outcome of this project will support the development of natural products to manage metabolic syndrome and prevent type 2 diabetes.
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Hydrogel systems for effective encapsulation of functional pancreatic islet cells. This proposal addresses the problem of maintaining viability and function of cells encapsulated within an immuno-isolation barrier material. The research will develop biosynthetic materials that are able to meet design criteria for an effective biomaterial for this application. The major benefits to Australia will be in improved health outcomes by providing safer, more efficacious materials, economic growth develo ....Hydrogel systems for effective encapsulation of functional pancreatic islet cells. This proposal addresses the problem of maintaining viability and function of cells encapsulated within an immuno-isolation barrier material. The research will develop biosynthetic materials that are able to meet design criteria for an effective biomaterial for this application. The major benefits to Australia will be in improved health outcomes by providing safer, more efficacious materials, economic growth development of the Australian Medical Device industry and in high level training of researchers in this field.Read moreRead less
Molecular basis of G protein receptor-effector coupling in epithelial cells. Hundreds of extracellular stimuli act on specific receptors in the plasma membrane of cells resulting in an increase in intracellular calcium which acts as a second messenger to alter cell behaviour. There are, however, many receptors acting through a number of closely related proteins involving tightly regulated interactions which remain poorly understood. This project uses novel techniques to elucidate the molecular b ....Molecular basis of G protein receptor-effector coupling in epithelial cells. Hundreds of extracellular stimuli act on specific receptors in the plasma membrane of cells resulting in an increase in intracellular calcium which acts as a second messenger to alter cell behaviour. There are, however, many receptors acting through a number of closely related proteins involving tightly regulated interactions which remain poorly understood. This project uses novel techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in this complex process.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775746
Funder
Australian Research Council
Funding Amount
$102,000.00
Summary
GC/MS facility for medical, bioanalytical and environmental research. The research will contribute to the bioremediation of heavily polluted sites in Sydney and the knowledge gained and the technology developed will be applicable to sites all over the world. Fundamental knowledge in Systems Biology will have applications to advance Australian export industries based on fermentation. Advances in chemical ecology and biotechnology will impact in areas such as contact lenses, implants, therapeutics ....GC/MS facility for medical, bioanalytical and environmental research. The research will contribute to the bioremediation of heavily polluted sites in Sydney and the knowledge gained and the technology developed will be applicable to sites all over the world. Fundamental knowledge in Systems Biology will have applications to advance Australian export industries based on fermentation. Advances in chemical ecology and biotechnology will impact in areas such as contact lenses, implants, therapeutics and water treatment. Probing pituitary hormone action will lead to greater understanding of health issues such as abnormal body composition, obesity and diabetes.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883078
Funder
Australian Research Council
Funding Amount
$356,000.00
Summary
Liquid Chromatography Tandem Mass Spectrometry Steroid Analysis Facility. This first of a new generation of ultra-sensitive analytical mass spectrometers for small molecules will be established as a national assay facility allowing all Australian researchers open access to a new dimension of highly accurate and simultaneous measurements of multiple bodily chemicals such as steroids, vitamins and hormones. It is crucial to developing new knowledge in basic, developmental and pathological cell bio ....Liquid Chromatography Tandem Mass Spectrometry Steroid Analysis Facility. This first of a new generation of ultra-sensitive analytical mass spectrometers for small molecules will be established as a national assay facility allowing all Australian researchers open access to a new dimension of highly accurate and simultaneous measurements of multiple bodily chemicals such as steroids, vitamins and hormones. It is crucial to developing new knowledge in basic, developmental and pathological cell biology and for underpinning commercial developments of new molecular targets for therapeutic drugs for many diseases including cancer, cardiovascular disease and reproductive disorders. This facility is pivotal to maintaining international competitiveness in many areas of biological research in national priority areas.Read moreRead less
Value Of Androgen Deprivation And Bisphosphonate In Patients Treated By Radiotherapy For Localised Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$2,533,827.00
Summary
Following on from significant findings in the TROG 96.01 trial, the 03.04 trial, known as the RADAR trial was developed. This is a large-scale randomised controlled clinical trial currently conducted at 23 cancer treatment centres throughout Australia and New Zealand. The RADAR trial aims to recruit 1000 men with localised but inoperable prostate cancer. It was anticipated that the length of time required to enrol 1000 participants to the trial would be 5 years. However, because enrolment has ex ....Following on from significant findings in the TROG 96.01 trial, the 03.04 trial, known as the RADAR trial was developed. This is a large-scale randomised controlled clinical trial currently conducted at 23 cancer treatment centres throughout Australia and New Zealand. The RADAR trial aims to recruit 1000 men with localised but inoperable prostate cancer. It was anticipated that the length of time required to enrol 1000 participants to the trial would be 5 years. However, because enrolment has exceeded expectations and 728 patients have already been recruited, it is anticipated that the recruitment target will be reached in mid 2007. Patients are randomly assigned to receive one of four treatment options in the RADAR trial. The first option: Option A: Radiation Therapy and 6 months of Hormone Therapy (Leuprorelin acetate), is currently the standard of care. Option C is a further 12 months of hormone therapy after the current standard of care. Two of the options (B and D) are identical to options A and C except that subjects also receive 18 months of zoledronate (a 'bone' drug) in addition to hormone therapy and radiotherapy. The main goal of the RADAR trial is to determine whether 12 months of hormone therapy using Leuprorelin acetate starting immediately after standard therapy (ie 6 months of Leuprorelin acetate before and during radiotherapy) will reduce risk of return of the cancer, either within the prostate region or at remote sites in the body, and prolong life. An additional goal is to see whether 18 months of bisphosphonate therapy (bone density therapy) using zoledronate will reduce the risk of cancer returning in the bones as well as stopping dangerous bone thinning which can sometimes be caused by hormone therapy. The trial also seeks to determine whether the additional therapy given in this trial alters quality of life.Read moreRead less