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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989920
Funder
Australian Research Council
Funding Amount
$750,000.00
Summary
Microbial and Cellular Imaging and Analysis Facility. The Microbial and Cellular Imaging and Analysis Facility will rapidly establish itself as one of Australia's premier science facilities. It will provide the capacity to investigate the structure and molecular dynamics of viruses and microbial, human, animal and plant cells with unprecedented high resolution in both pure and applied research settings, guided by Australia's leading experts in many research strengths. This facility addresses a c ....Microbial and Cellular Imaging and Analysis Facility. The Microbial and Cellular Imaging and Analysis Facility will rapidly establish itself as one of Australia's premier science facilities. It will provide the capacity to investigate the structure and molecular dynamics of viruses and microbial, human, animal and plant cells with unprecedented high resolution in both pure and applied research settings, guided by Australia's leading experts in many research strengths. This facility addresses a current unmet need for scientists in this country and will provide cutting-edge technologies to Australian researchers so they can better detect, understand, and treat human, animal and plant diseases and the environmental impact of climate change.Read moreRead less
Shaping the heart in early development - new insights into cellular modelling processes. Heart health is an important contributor to quality of life and longevity. This research will provide new insights into the way hormonal influences early in development shape a healthy heart. The project builds on the application of recently patented, sophisticated cell imaging techniques. Research students and trainees recruited to this project will benefit from their involvement with this leading edge tech ....Shaping the heart in early development - new insights into cellular modelling processes. Heart health is an important contributor to quality of life and longevity. This research will provide new insights into the way hormonal influences early in development shape a healthy heart. The project builds on the application of recently patented, sophisticated cell imaging techniques. Research students and trainees recruited to this project will benefit from their involvement with this leading edge technology. These studies are important in providing a basis for developing optimal management strategies for congenital heart conditions and preterm infants. Improved knowledge of the cardiac effects of fetal and neonatal exposure to steroids (to assist with lung maturation in prematurity or to control maternal asthma) will be gained.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
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
The role of SGK-1 and SGK-2 in hypertension and nephropathy in diabetes mellitus. The key objective is to define the suitability of the serum glucocorticoid regulated kinases -1 and -2 (SGK-1, -2) as novel drug discovery targets. A specific inhibitor targeting SGK-1 and -2 will be tested to determine if it reverses the enhanced sodium reabsorption and extracellular matrix production characteristic of progressive renal failure in in vitro models models of renal disease. These inhibitors present a ....The role of SGK-1 and SGK-2 in hypertension and nephropathy in diabetes mellitus. The key objective is to define the suitability of the serum glucocorticoid regulated kinases -1 and -2 (SGK-1, -2) as novel drug discovery targets. A specific inhibitor targeting SGK-1 and -2 will be tested to determine if it reverses the enhanced sodium reabsorption and extracellular matrix production characteristic of progressive renal failure in in vitro models models of renal disease. These inhibitors present an opportunity to control hypertension whilst simultaneously limiting fibrosis in the kidney. Renal failure is steadily increasing and is now the single largest health care cost to the community. These studies will provide the proof of concept required to ultimately bring this novel preventative therapy to the community.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.
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