Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in ....Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in the levels of nitric oxide in the body are associated with several diseases states and states of dysfunction including cardiovascular disease, diabetes and also impotence. Professor Triggle's study seeks to characterize how tissues may store nitric oxide, thus prolonging the life of nitric oxide, and how such stores are released. Read moreRead less
Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studi ....Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studies to investigate the effects of drugs that affect estrogen action and environmental estrogens. Read moreRead less
Investigation of the function of Sel S a novel selenoprotein. The long term aim of this project is to find a way to prevent or delay the onset of both Type 1 and Type 2 diabetes. ChemGenex pharmaceuticals, our commercial partners have discovered and patented a selenoprotein with antioxidant properties and have shown in vitro that it protects insulin-producing beta cells from oxidative damage. This project aims to prove, in an in vivo setting, that this protein can prevent or delay the onset of d ....Investigation of the function of Sel S a novel selenoprotein. The long term aim of this project is to find a way to prevent or delay the onset of both Type 1 and Type 2 diabetes. ChemGenex pharmaceuticals, our commercial partners have discovered and patented a selenoprotein with antioxidant properties and have shown in vitro that it protects insulin-producing beta cells from oxidative damage. This project aims to prove, in an in vivo setting, that this protein can prevent or delay the onset of diabetes in mouse models of type 1 and Type 2 diabetes.Read moreRead less
Developmental programming of adult stress responses: early life nutrition permanently alters stress and immune function. Obese children are more likely to grow up to be obese adults than normal-weight children are. Their early life diet may be at least partly to blame. Early life nutrition can also compromise ability to respond to stress or inflammation. This project will investigate how this occurs and if these effects are specific to the developmental period.
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
Masterminding Reproduction: Kisspeptin and RFamide-Related Peptide. There are a number of concerning trends in reproductive health. Women are reporting difficulty conceiving and maintaining pregnancies; while sperm count and quality are declining in men. More concerning is the increase in reproductive cancers. Gonadotropin-releasing hormone (GnRH) antagonist and agonist have been used for decades to treat reproductive cancers (such as breast cancer and prostate cancer), infertility and precociou ....Masterminding Reproduction: Kisspeptin and RFamide-Related Peptide. There are a number of concerning trends in reproductive health. Women are reporting difficulty conceiving and maintaining pregnancies; while sperm count and quality are declining in men. More concerning is the increase in reproductive cancers. Gonadotropin-releasing hormone (GnRH) antagonist and agonist have been used for decades to treat reproductive cancers (such as breast cancer and prostate cancer), infertility and precocious puberty. Kisspeptin and RF-related peptide may offer more physiological alternatives to GnRH, without detrimental side effects. We will fully explore these two newly defined and major players in reproduction and provide a physiological framework for their progression to clinical use.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0452281
Funder
Australian Research Council
Funding Amount
$102,900.00
Summary
Muscle Vascular Research and Gene Therapy Using Ultrasound. We seek funds to set up a national facility for ultrasound in muscle vascular research and gene therapy. Ultrasound with microbubbles will be used for the imaging of muscle microvascular blood flow and as a delivery modality for gene constructs to endothelial cells that control blood flow. The technology has application to (i) the assessment and therapeutic treatment of impaired microvascular function as in diabetics; (ii) the assessmen ....Muscle Vascular Research and Gene Therapy Using Ultrasound. We seek funds to set up a national facility for ultrasound in muscle vascular research and gene therapy. Ultrasound with microbubbles will be used for the imaging of muscle microvascular blood flow and as a delivery modality for gene constructs to endothelial cells that control blood flow. The technology has application to (i) the assessment and therapeutic treatment of impaired microvascular function as in diabetics; (ii) the assessment of adaptation to physical training and (iii) the development of therapeutic agents used to treat diabetes. We anticipate improved technology that is fully characterized and novel therapeutics that improve microvascular blood flow.Read moreRead less
Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to imp ....Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to improve its properties and reduce potential side-effects. The outcomes of this project will be understanding of a new biological process that contributes to the development of diabetes, and the discovery and characterisation of new chemical compounds that could be developed as drugs to treat diabetes.Read moreRead less
Fluid mechanics and physiology of blockages in vascular systems. Vascular disease is a major health problem both in Australia and worldwide. In particular, cardiovascular disease is a major killer of adult Australians. Engineers and mathematicians working with biologists will gain a greater understanding of vascular diseases, a major health problem, including cardiovascular disease, which is one of the biggest killers worldwide, as well as tackling renal circulation problems, which are a signifi ....Fluid mechanics and physiology of blockages in vascular systems. Vascular disease is a major health problem both in Australia and worldwide. In particular, cardiovascular disease is a major killer of adult Australians. Engineers and mathematicians working with biologists will gain a greater understanding of vascular diseases, a major health problem, including cardiovascular disease, which is one of the biggest killers worldwide, as well as tackling renal circulation problems, which are a significant problem and may contribute to hypertension. Detailed measurement and prediction will be undertaken of the mechanical loading and response of cells to their microenvironment, an important first step to controlling pathological responses which lead to a variety of autoimmune problems.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