Structural Studies Of Thyroid Peroxidase, An Autoantigen In Autoimmune Thyroid Disease
Funder
National Health and Medical Research Council
Funding Amount
$386,423.00
Summary
This proposal is aimed at determining the three dimensional structure of Thyroid Peroxidase, a protein found in the human thyroid gland that is important in the production of the hormone thyroxine. Thyroxine is involved in controlling the rate of metabolic processes in the body and influencing physical development.
Open-label Randomised Trial Of Tolvaptan Versus Fluid Restriction In Hospitalised Patients With Moderate-severe Hyponatraemia
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Low blood sodium level, known as hyponatraemia, is the most common electrolyte problem. It occurs in 15% of hospital patients, and can cause confusion, seizure and fatal brain swelling. Standard treatment for hyponatraemia is limiting oral fluid, but this is slow and not always effective. The drug tolvaptan works in mild hyponatraemia, but hasn't been formally tested in severe cases. We will compare benefits and risks of tolvaptan versus fluid restriction in patients with severe hyponatremia.
A Novel Approach To Streamlining The Diagnosis Of Primary Aldosteronism
Funder
National Health and Medical Research Council
Funding Amount
$269,463.00
Summary
This study will assess a new clinical test used to diagnose a potentially curable form of high blood pressure called primary aldosteronism (PA). If successful, the test will greatly streamline and simplify the diagnosis of this condition, with the potential for enormous cost savings and a markedly increased rate of diagnosis of patients with PA who can then benefit from optimal treatment and improved quality of life.
Elucidating Genetic Mechanisms Responsible For Familial Hyperaldosteronism Type II
Funder
National Health and Medical Research Council
Funding Amount
$424,812.00
Summary
Primary aldosteronism (PAL) is the commonest specifically treatable and potentially curable form of hypertension (high blood pressure), a common disease, expensive to treat, with serious morbidity and mortality. This project will use cutting edge technology to gain new knowledge concerning how genes regulate the body's production of aldosterone (salt hormone), which will help us understand how PAL develops and how common it is, and could lead to better approaches to diagnosis and treatment.
Hypothalamic Regulation Of Appetite And Energy Homeostasis In Prader-Willi Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$39,987.00
Summary
Prader-Willi syndrome (PWS) is a genetic disease affecting 1/~15 000 people. It causes insatiable appetite and often morbid obesity, as well as other developmental problems. It is thought that there is a defect in the way that the brain regulates eating behaviour in PWS, but the exact mechanism is still unknown. This study proposes to explore metabolic and genetic factors contributing to the appetite disorder in PWS. It will also explore new ways of treating excessive appetite.
Understanding The Control Of Brain Development And Endocrine Function Through Central Regulation Of Gene Transcription
Funder
National Health and Medical Research Council
Funding Amount
$624,846.00
Summary
Intellectual disability affects about 2% of the Australian population. The identification of genes underlying a number of intellectual disability disorders has brought about great clinical advances. However, our knowledge of how these genes influence processes of brain development and are important for intelligence is very limited. We propose to study the function of PHF6, the gene mutated in the Börjeson-Forssman-Lehmann intellectual disability syndrome, during brain development.
Fetal And Genetic Origins Of Polycystic Ovary Syndrome (PCOS) In Young Women
Funder
National Health and Medical Research Council
Funding Amount
$449,073.00
Summary
Polycystic ovary syndrome (PCOS) is a common hormonal condition which emerges at puberty and afflicts up to 10% of women. The cause of PCOS is uncertain. Symptoms include menstrual disorders, acne, obesity, and excess body hair. PCOS is of great significance for women because of the high incidence of infertility and the high risk of other serious diseases, including diabetes mellitus and endometrial cancer. PCOS is probably the most common hormonal condition among young women. The cause of PCOS ....Polycystic ovary syndrome (PCOS) is a common hormonal condition which emerges at puberty and afflicts up to 10% of women. The cause of PCOS is uncertain. Symptoms include menstrual disorders, acne, obesity, and excess body hair. PCOS is of great significance for women because of the high incidence of infertility and the high risk of other serious diseases, including diabetes mellitus and endometrial cancer. PCOS is probably the most common hormonal condition among young women. The cause of PCOS is unknown and the relationship between PCOS and the more common condition of polycystic ovaries, which often features in PCOS, is uncertain. There is evidence that genetic factors contribute to PCOS, but cannot explain certain aspects. There is also striking new evidence that abnormal growth in the womb can alter the metabolism of the baby for life, resulting in increased risks of adult disease, including diabetes and cardiovascular disease. PCOS may be another consequence of abnormal fetal growth, a suggestion that is supported by two recent studies of closely related conditions. To investigate the origins of PCOS, we propose to establish the first international study of the relationships between fetal growth, genetic factors and the presence of PCOS. In this study, we shall trace 3,260 women born in one maternity ward during 1973-75. These women, now young adults, will be invited into our study for an interview, physical examination, and a blood test. We expect 2,200 women will participate. Of this group, some 220 women with PCOS will receive further tests to investigate a range of metabolic problems. The study has the potential to illuminate the path from genetic predisposition and fetal growth, to the emergence of an important reproductive disorder with serious associated diseases in a woman s later life.Read moreRead less
Enrichment, Differentiation And Functional Analysis Of Growth Hormone Progenitor Cells From The Adult Mouse Pituitary
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
Many important bodily functions including growth, metabolism, onset of puberty, fertility, lactation and the ability to cope with stress are controlled by hormones secreted by the pituitary gland. Consequently, insufficient hormone production by the pituitary gland (hypopituitarism) results in life-threatening conditions which are a significant clinical problem. Growth Hormone (GH) deficiency is the most common form of pituitary hormone deficiency, affecting 1:3,500 individuals. Currently, GH de ....Many important bodily functions including growth, metabolism, onset of puberty, fertility, lactation and the ability to cope with stress are controlled by hormones secreted by the pituitary gland. Consequently, insufficient hormone production by the pituitary gland (hypopituitarism) results in life-threatening conditions which are a significant clinical problem. Growth Hormone (GH) deficiency is the most common form of pituitary hormone deficiency, affecting 1:3,500 individuals. Currently, GH deficiency is treated by daily injections of growth hormone at a cost of $30,000 to $50,000 per patient per annum. However, even with daily injections and despite the cost, it is difficult to mimic the naturally fluctuating hormone levels in the body, resulting in incomplete growth rescue. Long term injections also have severe side effects that can lead to cardiovascular problems, abnormal bone density, diabetes and cancers of various types. To overcome the disadvantages of hormone therapy we are investigating a new cell replacement therapy to treat GH deficiency. This approach requires knowledge about the mechanism by which GH-secreting cells are generated and maintained in the adult pituitary. For the first time, we have isolated a type of progenitor (unspecialised) cell from adult mouse pituitary that is capable of dividing and generating GH-secreting cells. Our current research aims to further purify these cells and to show that they are capable of secreting GH in response to biologically relevant signals. In addition, we will test whether these cells can grow and develop into functional cells when introduced into mice. In particular, we will test whether the progenitor cells can rescue dwarfism using a mouse model of GH deficiency. This pioneering study will provide the first insight into the possibility of cell therapy for the pituitary, and may ultimately lead to the development of better therapies for patients with GH deficiency.Read moreRead less
RCAN1 IS A MASTER REGULATOR OF BETA CELL FUNCTION AND INSULIN SECRETION
Funder
National Health and Medical Research Council
Funding Amount
$446,610.00
Summary
Type 2 diabetes affects over 1.5 million Australians and is caused by insufficient insulin release by beta cells in the pancreas. We have discovered a new regulator of insulin secretion called RCAN1 and we now aim to understand how this regulation occurs. We also believe RCAN1 may be responsible for the transition from healthy to dysfunctional beta cell in Type 2 diabetes and this project will identify whether this is the case.
The Fetal And Early Childhood Origins Of PCOS: A Prospective Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$499,116.00
Summary
The Polycystic Ovary Syndrome (PCOS) affects up to 10% of women of reproductive age, which translates into around 350,000 women in Australia. It is the most common hormonal disorder in women. The syndrome has far-reaching adverse implications for general and reproductive health, including menstrual disorder, obesity, infertility, miscarriage, pregnancy complications, increased risk of diabetes and possibly heart disease. PCOS also commonly causes cosmetic problems such as excess body hair and ac ....The Polycystic Ovary Syndrome (PCOS) affects up to 10% of women of reproductive age, which translates into around 350,000 women in Australia. It is the most common hormonal disorder in women. The syndrome has far-reaching adverse implications for general and reproductive health, including menstrual disorder, obesity, infertility, miscarriage, pregnancy complications, increased risk of diabetes and possibly heart disease. PCOS also commonly causes cosmetic problems such as excess body hair and acne. The underlying causes of PCOS are not known but are thought to arise during intrauterine (fetal) life and to be modified by aspects of childhood health, particularly overweight and obesity. Using a large and well established cohort of adolescents followed up since fetal life and throughout childhood and currently aged 13-15 years old (the Raine cohort), we will define for the first time the intrauterine and early childhood correlates of PCOS. PCOS will be diagnosed by a specialist gynacologist using current international criteria. We will then utilise extensive existing data from this cohort combined with new measurements on existing samples to determine the contribution of key factors including fetal growth restriction, low birth weight, fetal androgen exposure, rapid postnatal growth, childhood adiposity, elevated fasting glucose and insulin and age at menarche to PCOS. In this way, we will address for the first time the hypothesis that PCOS arises as a result of events during fetal life and is affected by factors during childhood. The results from these studies will improve our understanding of PCOS and eventually improve reproductive and metabolic health for a substantial population of women internationally. It is essential that these studies are conducted as soon as possible or the opportunity will be missed. Girls with persistent menstrual irregularity are likely to be commenced on hormonal treatments which will make the diagnosis of PCOS impossible.Read moreRead less